Base de dados : MEDLINE
Pesquisa : B01.050.150.900.649.801.400.112.199.120.510.550 [Categoria DeCS]
Referências encontradas : 36240 [refinar]
Mostrando: 1 .. 10   no formato [Longo]

página 1 de 3624 ir para página                         

  1 / 36240 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28441902
Autor:Singh VK; Olabisi AO
Endereço:a Department of Pharmacology and Molecular Therapeutics , F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences , Bethesda , MD , USA.
Título:Nonhuman primates as models for the discovery and development of radiation countermeasures.
Fonte:Expert Opin Drug Discov; 12(7):695-709, 2017 Jul.
ISSN:1746-045X
País de publicação:England
Idioma:eng
Resumo:INTRODUCTION: Despite significant scientific advances over the past six decades toward the development of safe and effective radiation countermeasures for humans using animal models, only two pharmaceutical agents have been approved by United States Food and Drug Administration (US FDA) for hematopoietic acute radiation syndrome (H-ARS). Additional research efforts are needed to further develop large animal models for improving the prediction of clinical safety and effectiveness of radiation countermeasures for ARS and delayed effects of acute radiation exposure (DEARE) in humans. Area covered: The authors review the suitability of animal models for the development of radiation countermeasures for ARS following the FDA Animal Rule with a special focus on nonhuman primate (NHP) models of ARS. There are seven centers in the United States currently conducting studies with irradiated NHPs, with the majority of studies being conducted with rhesus monkeys. Expert opinion: The NHP model is considered the gold standard animal model for drug development and approval by the FDA. The lack of suitable substitutes for NHP models for predicting response in humans serves as a bottleneck for the development of radiation countermeasures. Additional large animal models need to be characterized to support the development and FDA-approval of new radiation countermeasures.
Tipo de publicação: JOURNAL ARTICLE; REVIEW
Nome de substância:0 (Radiation-Protective Agents)


  2 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28208025
Autor:MacVittie TJ; Gibbs A; Farese AM; Barrow K; Bennett A; Taylor-Howell C; Kazi A; Prado K; Parker G; Iii WJ
Endereço:a Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, Maryland.
Título:AEOL 10150 Mitigates Radiation-Induced Lung Injury in the Nonhuman Primate: Morbidity and Mortality are Administration Schedule-Dependent.
Fonte:Radiat Res; 187(3):298-318, 2017 Mar.
ISSN:1938-5404
País de publicação:United States
Idioma:eng
Resumo:Pneumonitis and fibrosis are potentially lethal, delayed effects of acute radiation exposure. In this study, male rhesus macaques received whole-thorax lung irradiation (WTLI) with a target dose of 10.74 Gy prescribed to midplane at a dose rate of 0.80 ± 0.05 Gy/min using 6 MV linear accelerator-derived photons. The study design was comprised of four animal cohorts: one control and three treated with AEOL 10150 (n = 20 animals per cohort). AEOL 10150, a metalloporphyrin antioxidant, superoxide dismutase mimetic was administered by daily subcutaneous injection at 5 mg/kg in each of three schedules, beginning 24 ± 2 h postirradiation: from day 1 to day 28, day 1 to day 60 or a divided regimen from day 1 to day 28 plus day 60 to day 88. Control animals received 0.9% saline injections from day 1 to day 28. All animals received medical management and were followed for 180 days. Computed tomography (CT) scan and baseline hematology values were assessed prior to WTLI. Postirradiation monthly CT scans were collected, and images were analyzed for evidence of lung injury (pneumonitis, fibrosis, pleural and pericardial effusion) based on differences in radiodensity characteristics of the normal versus damaged lung. The primary end point was survival to 180 days based on all-cause mortality. The latency, incidence and severity of lung injury were assessed through clinical, radiographic and histological parameters. A clear survival relationship was observed with the AEOL 10150 treatment schedule and time after lethal WTLI. The day 1-60 administration schedule increased survival from 25 to 50%, mean survival time of decedents and the latency to nonsedated respiratory rate to >60 or >80 breaths/min and diminished quantitative radiographic lung injury as determined by CT scans. It did not affect incidence or severity of pneumonitis/fibrosis as determined by histological evaluation, pleural effusion or pericardial effusion as determined by CT scans. Analysis of the Kaplan-Meier survival curves suggested that treatment efficacy could be increased by extending the treatment schedule to 90 days or longer after WTLI. No survival improvement was noted in the AEOL 10150 cohorts treated from day 1-28 or using the divided schedule of day 1-28 plus day 60-88. These results suggest that AEOL 10150 may be an effective medical countermeasure against severe and lethal radiation-induced lung injury.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (AEOL 10150); 0 (Metalloporphyrins)


  3 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28450546
Autor:Sun Y; Yang Y; Galvin VC; Yang S; Arnsten AF; Wang M
Endereço:Department of Neurology, Peking University First Hospital, Beijing 100034.
Título:Nicotinic α4ß2 Cholinergic Receptor Influences on Dorsolateral Prefrontal Cortical Neuronal Firing during a Working Memory Task.
Fonte:J Neurosci; 37(21):5366-5377, 2017 May 24.
ISSN:1529-2401
País de publicação:United States
Idioma:eng
Resumo:The primate dorsolateral prefrontal cortex (dlPFC) subserves top-down regulation of attention and working memory abilities. Depletion studies show that the neuromodulator acetylcholine (ACh) is essential to dlPFC working memory functions, but the receptor and cellular bases for cholinergic actions are just beginning to be understood. The current study found that nicotinic receptors comprised of α4 and ß2 subunits (α4ß2-nAChR) enhance the task-related firing of delay and fixation cells in the dlPFC of monkeys performing a working memory task. Iontophoresis of α4ß2-nAChR agonists increased the neuronal firing and enhanced the spatial tuning of delay cells, neurons that represent visual space in the absence of sensory stimulation. These enhancing effects were reversed by coapplication of a α4ß2-nAChR antagonist, consistent with actions at α4ß2-nAChR. Delay cell firing was reduced when distractors were presented during the delay epoch, whereas stimulation of α4ß2-nAChR protected delay cells from these deleterious effects. Iontophoresis of α4ß2-nAChR agonists also enhanced the firing of fixation cells, neurons that increase firing when the monkey initiates a trial, and maintain firing until the trial is completed. These neurons are thought to contribute to sustained attention and top-down motor control and have never before been the subject of pharmacological inquiry. These findings begin to build a picture of the cellular actions underlying the beneficial effects of ACh on attention and working memory. The data may also help to explain why genetic insults to α4 subunits are associated with working memory and attentional deficits and why α4ß2-nAChR agonists may have therapeutic potential. The acetylcholine (ACh) arousal system in the brain is needed for robust attention and working memory functions, but the receptor and cellular bases for its beneficial effects are poorly understood in the newly evolved primate brain. The current study found that ACh stimulation of nicotinic receptors comprised of α4 and ß2 subunits (α4ß2-nAChR) enhanced the firing of neurons in the primate prefrontal cortex that subserve top-down attentional control and working memory. α4ß2-nAChR stimulation also protected neuronal responding from the detrimental effects of distracters presented during the delay epoch, when information is held in working memory. These results illuminate how ACh strengthens higher cognition and help to explain why genetic insults to the α4 subunit weaken cognitive and attentional abilities.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Nicotinic Agonists); 0 (Receptors, Nicotinic); 0 (nicotinic receptor alpha4beta2)


  4 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28432139
Autor:Downer JD; Rapone B; Verhein J; O'Connor KN; Sutter ML
Endereço:Center for Neuroscience, University of California, Davis, California 95618.
Título:Feature-Selective Attention Adaptively Shifts Noise Correlations in Primary Auditory Cortex.
Fonte:J Neurosci; 37(21):5378-5392, 2017 May 24.
ISSN:1529-2401
País de publicação:United States
Idioma:eng
Resumo:Sensory environments often contain an overwhelming amount of information, with both relevant and irrelevant information competing for neural resources. Feature attention mediates this competition by selecting the sensory features needed to form a coherent percept. How attention affects the activity of populations of neurons to support this process is poorly understood because population coding is typically studied through simulations in which one sensory feature is encoded without competition. Therefore, to study the effects of feature attention on population-based neural coding, investigations must be extended to include stimuli with both relevant and irrelevant features. We measured noise correlations ( ) within small neural populations in primary auditory cortex while rhesus macaques performed a novel feature-selective attention task. We found that the effect of feature-selective attention on depended not only on the population tuning to the attended feature, but also on the tuning to the distractor feature. To attempt to explain how these observed effects might support enhanced perceptual performance, we propose an extension of a simple and influential model in which shifts in can simultaneously enhance the representation of the attended feature while suppressing the distractor. These findings present a novel mechanism by which attention modulates neural populations to support sensory processing in cluttered environments. Although feature-selective attention constitutes one of the building blocks of listening in natural environments, its neural bases remain obscure. To address this, we developed a novel auditory feature-selective attention task and measured noise correlations ( ) in rhesus macaque A1 during task performance. Unlike previous studies showing that the effect of attention on depends on population tuning to the attended feature, we show that the effect of attention depends on the tuning to the distractor feature as well. We suggest that these effects represent an efficient process by which sensory cortex simultaneously enhances relevant information and suppresses irrelevant information.
Tipo de publicação: JOURNAL ARTICLE


  5 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28143858
Autor:Shang J; Previs SF; Conarello S; Chng K; Zhu Y; Souza SC; Staup M; Chen Y; Xie D; Zycband E; Schlessinger K; Johnson VP; Arreaza G; Liu F; Levitan D; Wang L; van Heek M; Erion M; Wang Y; Kelley DE
Endereço:Merck & Company, Incorporated, Kenilworth, New Jersey; and shangjin63@gmail.com.
Título:Phenotyping of adipose, liver, and skeletal muscle insulin resistance and response to pioglitazone in spontaneously obese rhesus monkeys.
Fonte:Am J Physiol Endocrinol Metab; 312(4):E235-E243, 2017 Apr 01.
ISSN:1522-1555
País de publicação:United States
Idioma:eng
Resumo:Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus were undertaken to assess hepatic and adipose contributions to systemic insulin resistance-currently, a gap in our knowledge-and to benchmark the responses to pioglitazone (PIO). A two-step hyperinsulinemic-euglycemic clamp, with tracer-based glucose flux estimates, was used to measure insulin resistance, and in an intervention study was repeated following 6 wk of PIO treatment (3 mg/kg). Compared with lean healthy rhesus, obese rhesus has a 60% reduction of glucose utilization during a high insulin infusion and markedly impaired suppression of lipolysis, which was evident at both low and high insulin infusion. However, obese dysmetabolic rhesus manifests only mild hepatic insulin resistance. Six-week PIO treatment significantly improved skeletal muscle and adipose insulin resistance (by ~50%). These studies strengthen the concept that insulin resistance in obese rhesus closely resembles human insulin resistance and indicate the value of obese rhesus for appraising new insulin-sensitizing therapeutics.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Blood Glucose); 0 (Hypoglycemic Agents); 0 (Thiazolidinediones); X4OV71U42S (pioglitazone)


  6 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28135258
Autor:Vitak SA; Torkenczy KA; Rosenkrantz JL; Fields AJ; Christiansen L; Wong MH; Carbone L; Steemers FJ; Adey A
Endereço:Department of Molecular &Medical Genetics, Oregon Health &Science University, Portland, Oregon, USA.
Título:Sequencing thousands of single-cell genomes with combinatorial indexing.
Fonte:Nat Methods; 14(3):302-308, 2017 Mar.
ISSN:1548-7105
País de publicação:United States
Idioma:eng
Resumo:Single-cell genome sequencing has proven valuable for the detection of somatic variation, particularly in the context of tumor evolution. Current technologies suffer from high library construction costs, which restrict the number of cells that can be assessed and thus impose limitations on the ability to measure heterogeneity within a tissue. Here, we present single-cell combinatorial indexed sequencing (SCI-seq) as a means of simultaneously generating thousands of low-pass single-cell libraries for detection of somatic copy-number variants. We constructed libraries for 16,698 single cells from a combination of cultured cell lines, primate frontal cortex tissue and two human adenocarcinomas, and obtained a detailed assessment of subclonal variation within a pancreatic tumor.
Tipo de publicação: JOURNAL ARTICLE


  7 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28027479
Autor:Yuan Z; Ma F; Demers AJ; Wang D; Xu J; Lewis MG; Li Q
Endereço:Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA.
Título:Characterization of founder viruses in very early SIV rectal transmission.
Fonte:Virology; 502:97-105, 2017 Feb.
ISSN:1096-0341
País de publicação:United States
Idioma:eng
Resumo:A better understanding of HIV-1 transmission is critical for developing preventative strategies. To that end, we analyzed 524 full-length env sequences of SIVmac251 at 6 and 10 days post intrarectal infection of rhesus macaques. There was no tissue compartmentalization of founder viruses across plasma, rectal and distal lymphatic tissues for most animals; however one animal has evidence of virus tissue compartmentalization. Despite identical viral inoculums, founder viruses were animal-specific, primarily derived from rare variants in the inoculum, and have a founder virus signature that can distinguish dominant founder variants from minor founder or untransmitted variants in the inoculum. Importantly, the sequences of post-transmission defective viruses were phylogenetically associated with competent viral variants in the inoculum and were mainly converted from competent viral variants by frameshift rather than APOBEC mediated mutations, suggesting the converting the transmitted viruses into defective viruses through frameshift mutation is an important component of rectal transmission bottleneck. SIGNIFICANCE: Anorectal receptive intercourse is a common route of HIV-1 transmission and a better understanding of the transmission mechanisms is critical for developing HIV-1 preventative strategies. Here, we report that there is no tissue compartmentalization of founder viruses during very early rectal transmission of SIV in the majority of rhesus macaques and founder viruses are preferentially derived from rare variant in the inoculum. We also found that founder viruses are animal-specific despite identical viral inoculums. After viruses cross the mucosal barriers, the host further reduces viral diversity by converting some of the transmitted functional viruses into defective viruses through frameshift rather than APOBEC derived mutations. To our knowledge, this is the first study of founder viruses at multiple tissue sites during very early rectal transmission.
Tipo de publicação: JOURNAL ARTICLE


  8 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28438777
Autor:Weed PF; France CP; Gerak LR
Endereço:Departments of Pharmacology (P.F.W., C.P.F., L.R.G.) and Psychiatry (C.P.F.), and the Addiction Research, Treatment & Training Center of Excellence (P.F.W., C.P.F, L.R.G.), University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Título:Preference for an Opioid/Benzodiazepine Mixture over an Opioid Alone Using a Concurrent Choice Procedure in Rhesus Monkeys.
Fonte:J Pharmacol Exp Ther; 362(1):59-66, 2017 Jul.
ISSN:1521-0103
País de publicação:United States
Idioma:eng
Resumo:Increased abuse of opioids is contributing to an escalation in overdose deaths. Benzodiazepines are frequently abused with opioids, possibly because they increase the potency and/or effectiveness of opioids to produce reinforcing effects. This study used a concurrent-choice procedure to determine whether monkeys would choose to self-administer a mixture of the opioid remifentanil and the benzodiazepine midazolam over remifentanil alone. Initially, three monkeys could respond on one lever for saline and on a second lever for either remifentanil alone or midazolam alone. Thereafter, monkeys chose between a dose of remifentanil (0.32 g/kg/infusion) that did not change and a dose of remifentanil that varied across sessions; for some sessions, midazolam was combined with varying doses of remifentanil. All monkeys received more infusions of remifentanil (0.0032-0.32 g/kg/infusion) than saline, whereas only two monkeys responded more for midazolam than for saline. When 0.32 g/kg/infusion remifentanil was available on one lever and a dose of remifentanil that varied across sessions (0.1-1 g/kg/infusion) was available on the other lever, monkeys chose the larger dose. Combining 3.2 g/kg/infusion midazolam with 0.32 g/kg/infusion remifentanil increased responding for the mixture over 0.32 g/kg/infusion remifentanil alone, although monkeys chose remifentanil alone over mixtures containing smaller doses of remifentanil. When 10 g/kg/infusion midazolam was combined with 0.1 g/kg/infusion remifentanil, monkeys chose the mixture over 0.32 g/kg/infusion remifentanil alone. Thus, monkeys prefer some opioid/benzodiazepine mixtures to larger doses of the opioid alone, suggesting that opioid/benzodiazepine coabuse might be due to increased potency (and possibly effectiveness) of opioids to produce reinforcing effects.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Analgesics, Opioid); 0 (Drug Combinations); 0 (Piperidines); 12794-10-4 (Benzodiazepines); P10582JYYK (remifentanil)


  9 / 36240 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28243926
Autor:Wilsey L; Gowrisankaran S; Cull G; Hardin C; Burgoyne CF; Fortune B
Endereço:Discoveries in Sight Research Laboratories, Devers Eye Institute, Legacy Research Institute, Legacy Health, 1225 NE Second Avenue, Portland, OR, 97232, USA.
Título:Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure.
Fonte:Doc Ophthalmol; 134(2):111-128, 2017 Apr.
ISSN:1573-2622
País de publicação:Netherlands
Idioma:eng
Resumo:PURPOSE: To compare diagnostic performance and structure-function correlations of multifocal electroretinogram (mfERG), full-field flash ERG (ff-ERG) photopic negative response (PhNR) and transient pattern-reversal ERG (PERG) in a non-human primate (NHP) model of experimental glaucoma (EG). METHODS: At baseline and after induction of chronic unilateral IOP elevation, 43 NHP had alternating weekly recordings of retinal nerve fiber layer thickness (RNFLT) by spectral domain OCT (Spectralis) and retinal function by mfERG (7F slow-sequence stimulus, VERIS), ff-ERG (red 0.42 log cd-s/m flashes on blue 30 scotopic cd/m background, LKC UTAS-E3000), and PERG (0.8° checks, 99% contrast, 100 cd/m mean, 5 reversals/s, VERIS). All NHP were followed at least until HRT-confirmed optic nerve head posterior deformation, most to later stages. mfERG responses were filtered into low- and high-frequency components (LFC, HFC, >75 Hz). Peak-to-trough amplitudes of LFC features (N1, P1, N2) and HFC RMS amplitudes were measured and ratios calculated for HFC:P1 and N2:P1. ff-ERG parameters included A-wave (at 10 ms), B-wave (trough-to-peak) and PhNR (baseline-to-trough) amplitudes as well as PhNR:B-wave ratio. PERG parameters included P50 and N95 amplitudes as well as N95:P50 ratio and N95 slope. Diagnostic performance of retinal function parameters was compared using the area under the receiver operating characteristic curve (A-ROC) to discriminate between EG and control eyes. Correlations to RNFLT were compared using Steiger's test. RESULTS: Study duration was 15 ± 8 months. At final follow-up, structural damage in EG eyes measured by RNFLT ranged from 9% above baseline (BL) to 58% below BL; 29/43 EG eyes (67%) and 0/43 of the fellow control eyes exhibited significant (>7%) loss of RNFLT from BL. Using raw parameter values, the largest A-ROC findings for mfERG were: HFC (0.82) and HFC:P1 (0.90); for ff-ERG: PhNR (0.90) and PhNR:B-wave (0.88) and for PERG: P50 (0.64) and N95 (0.61). A-ROC increased when data were expressed as % change from BL, but the pattern of results persisted. At 95% specificity, the diagnostic sensitivity of mfERG HFC:P1 ratio was best, followed by PhNR and PERG. The correlation to RNFLT was stronger for mfERG HFC (R = 0.65) than for PhNR (R = 0.59) or PERG N95 (R = 0.36), (p = 0.20, p = 0.0006, respectively). The PhNR flagged a few EG eyes at the final time point that had not been flagged by mfERG HFC or PERG. CONCLUSIONS: Diagnostic performance and structure-function correlation were strongest for mfERG HFC as compared with ff-ERG PhNR or PERG in NHP EG.
Tipo de publicação: JOURNAL ARTICLE


  10 / 36240 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
PMID:28241007
Autor:Wirth S; Baraduc P; Planté A; Pinède S; Duhamel JR
Endereço:Centre de Neuroscience Cognitive, UMR 5229, CNRS and University of Lyon, Bron, France.
Título:Gaze-informed, task-situated representation of space in primate hippocampus during virtual navigation.
Fonte:PLoS Biol; 15(2):e2001045, 2017 Feb.
ISSN:1545-7885
País de publicação:United States
Idioma:eng
Resumo:To elucidate how gaze informs the construction of mental space during wayfinding in visual species like primates, we jointly examined navigation behavior, visual exploration, and hippocampal activity as macaque monkeys searched a virtual reality maze for a reward. Cells sensitive to place also responded to one or more variables like head direction, point of gaze, or task context. Many cells fired at the sight (and in anticipation) of a single landmark in a viewpoint- or task-dependent manner, simultaneously encoding the animal's logical situation within a set of actions leading to the goal. Overall, hippocampal activity was best fit by a fine-grained state space comprising current position, view, and action contexts. Our findings indicate that counterparts of rodent place cells in primates embody multidimensional, task-situated knowledge pertaining to the target of gaze, therein supporting self-awareness in the construction of space.
Tipo de publicação: JOURNAL ARTICLE



página 1 de 3624 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde