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1.
Redox Biol ; 60: 102599, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36640725

RESUMO

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.


Assuntos
Neoplasias de Cabeça e Pescoço , Insuficiência Renal Crônica , Humanos , Benchmarking , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Ferro/metabolismo , Rim/metabolismo , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/tratamento farmacológico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
2.
Appl Opt ; 56(18): 5274-5294, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29047582

RESUMO

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

4.
Behav Brain Res ; 308: 83-93, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27060720

RESUMO

Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans, the amygdala develops rapidly during the first two years of life. Thus, disturbed care during this period may be particularly important to amygdala development. In the context of a 30-year longitudinal study of impoverished, highly stressed families, we assessed whether disorganization of the attachment relationship in infancy was related to amygdala volume in adulthood. Amygdala volumes were assessed among 18 low-income young adults (8M/10F, 29.33±0.49years) first observed in infancy (8.5±5.6months) and followed longitudinally to age 29. In infancy (18.58±1.02mos), both disorganized infant attachment behavior and disrupted maternal communication were assessed in the standard Strange Situation Procedure (SSP). Increased left amygdala volume in adulthood was associated with both maternal and infant components of disorganized attachment interactions at 18 months of age (overall r=0.679, p<0.004). Later stressors, including childhood maltreatment and attachment disturbance in adolescence, were not significantly related to left amygdala volume. Left amygdala volume was further associated with dissociation and limbic irritability in adulthood. Finally, left amygdala volume mediated the prediction from attachment disturbance in infancy to limbic irritability in adulthood. Results point to the likely importance of quality of early care for amygdala development in human children as well as in rodents. The long-term prediction found here suggests that the first two years of life may be an early sensitive period for amygdala development during which clinical intervention could have particularly important consequences for later child outcomes.


Assuntos
Tonsila do Cerebelo/crescimento & desenvolvimento , Anomia (Social) , Apego ao Objeto , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Fatores de Risco , Adulto Jovem
5.
Med Hypotheses ; 80(5): 656-62, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23414680

RESUMO

There are many published studies about the epigenetic effects of the prenatal and infant periods on health outcomes. However, there is very little knowledge regarding the effects of the intrapartum period (labor and birth) on health and epigenetic remodeling. Although the intrapartum period is relatively short compared to the complete perinatal period, there is emerging evidence that this time frame may be a critical formative phase for the human genome. Given the debates from the National Institutes of Health and World Health Organization regarding routine childbirth procedures, it is essential to establish the state of the science concerning normal intrapartum epigenetic physiology. EPIIC (Epigenetic Impact of Childbirth) is an international, interdisciplinary research collaboration with expertise in the fields of genetics, physiology, developmental biology, epidemiology, medicine, midwifery, and nursing. We hypothesize that events during the intrapartum period - specifically the use of synthetic oxytocin, antibiotics, and cesarean section - affect the epigenetic remodeling processes and subsequent health of the mother and offspring. The rationale for this hypothesis is based on recent evidence and current best practice.


Assuntos
Cesárea , Epigênese Genética/genética , Epigenômica/métodos , Doenças do Recém-Nascido/genética , Trabalho de Parto/genética , Modelos Genéticos , Feminino , Humanos , Recém-Nascido , Gravidez
6.
Br J Pharmacol ; 170(8): 1449-58, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24528237

RESUMO

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Terapia de Alvo Molecular , Farmacologia , Humanos , Ligantes , Preparações Farmacêuticas/química
8.
Clin Genet ; 82(3): 248-55, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21801163

RESUMO

Corpus callosum abnormalities, intellectual disability, speech impairment, and autism in patients with haploinsufficiency of ARID1B. Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30-50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype-genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.


Assuntos
Anormalidades Múltiplas/genética , Agenesia do Corpo Caloso/genética , Transtorno Autístico/genética , Proteínas de Ligação a DNA/genética , Deficiência Intelectual/genética , Distúrbios da Fala/genética , Fatores de Transcrição/genética , Adulto , Pré-Escolar , Haploinsuficiência , Humanos , Masculino , Pessoa de Meia-Idade
9.
Clin Pharmacol Ther ; 89(5): 683-92, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21412231

RESUMO

Lorcaserin is a selective and potent serotonin 2C receptor subtype (5-HT(2C)) agonist under development for the treatment of obesity. This study assessed the drug's abuse potential on the basis of its pharmacological profile. For this purpose, a double-blind, double-dummy, placebo-controlled, randomized seven-way crossover study with single oral doses of lorcaserin (20, 40, and 60 mg), zolpidem (15 and 30 mg), ketamine (100 mg), and placebo was conducted in recreational polydrug users (N = 35). Subjective and objective measures were assessed up to 24 h after the dose. We found that zolpidem and ketamine had significantly higher peak scores relative to placebo on the primary measures as well as on most of the secondary measures. The subjective effects of a 20-mg dose of lorcaserin were similar to those of placebo, whereas supratherapeutic doses of lorcaserin were associated with significant levels of dislike by users as compared with placebo, zolpidem, and ketamine. Perceptual effects were minimal after administration of lorcaserin and significantly lower than after administration of either ketamine or zolpidem. The findings suggest that, at supratherapeutic doses, lorcaserin is associated with distinct, primarily negative, subjective effects and has low abuse potential.


Assuntos
Benzazepinas/uso terapêutico , Drogas Ilícitas , Agonistas do Receptor 5-HT2 de Serotonina/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Ketamina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/psicologia , Piridinas/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Adulto Jovem , Zolpidem
10.
Environ Technol ; 31(8-9): 979-91, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20662386

RESUMO

Molecular characterization of subsurface microbial communities in the former Homestake gold mine, South Dakota, was carried out by 16S rDNA sequence analysis using a water sample and a weathered soil-like sample. Geochemical analyses indicated that both samples were high in sulphur, rich in nitrogen and salt, but with significantly different metal concentrations. Microbial diversity comparisons unexpectedly revealed three distinct operational taxonomic units (OTUs) belonging to the archaeal phylum Thaumarchaeota, typically identified from marine environments, and one OTU belonging to a potentially novel phylum that fell sister to Thaumarchaeota. To our knowledge this is only the second report of Thaumarchaeota in a terrestrial environment. The majority of the clones from Archaea sequence libraries fell into two closely related OTUs and were grouped most closely to an ammonia-oxidizing, carbon-fixing and halophilic thaumarchaeote genus, Nitrosopumilus. The two samples showed neither Euryarchaeota nor Crenarchaeota members that have often been identified from other subsurface terrestrial ecosystems. Bacteria OTUs containing the highest percentage of sequences were related to sulphur-oxidizing bacteria of the orders Chromatiales and Thiotrichales. Community members of Bacteria from individual Homestake ecosystems were heterogeneous and distinctive to each community, with unique phylotypes identified within each sample.


Assuntos
Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Sedimentos Geológicos/microbiologia , Filogenia , Microbiologia do Solo , Microbiologia da Água , Archaea/genética , Bactérias/genética , Sequência de Bases , DNA Arqueal/química , DNA Arqueal/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Mineração , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Alinhamento de Sequência , Análise de Sequência de DNA , South Dakota
11.
J Dev Orig Health Dis ; 1(2): 131-40, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25143067

RESUMO

Little is known about the consequences of maternal copper (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring directly exposed to maternal Cu deficiency during development and lactation and perpetuation of the effects in a second generation of offspring. Dams were fed a diet with marginal (1 mg Cu/kg) or adequate (6 mg Cu/kg) Cu for 3 weeks before conception and throughout pregnancy and lactation periods. Half of the first generation (F1) litters were cross-fostered. At reproductive maturity, F1 pairs were bred within groups resulting in second generation (F2) offspring. At 9 weeks of age, mesenteric artery (200 µm) isometric tension was determined in response to vasoconstrictors and vasorelaxants using a small artery wire myograph. Cu deficiency did not alter the vascular function in dams. In F1 offspring, increased responsiveness to potassium chloride in male offspring was due to direct exposure to maternal Cu deficiency in the birth mother, while enhanced endothelium-dependent relaxation responses in female offspring resulted from postnatal exposure to maternal Cu deficiency. Increased endothelium independent and decreased endothelium-dependent relaxation responses were identified in F2 Cu-deficient male offspring. These data indicate that exposure to maternal Cu deficiency during critical windows of development alter the vascular function across two generations of offspring.

12.
Mol Ecol Resour ; 9(5): 1375-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21564911

RESUMO

This article documents the addition of 283 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Agalinis acuta; Ambrosia artemisiifolia; Berula erecta; Casuarius casuarius; Cercospora zeae-maydis; Chorthippus parallelus; Conyza canadensis; Cotesia sesamiae; Epinephelus acanthistius; Ficedula hypoleuca; Grindelia hirsutula; Guadua angustifolia; Leucadendron rubrum; Maritrema novaezealandensis; Meretrix meretrix; Nilaparvata lugens; Oxyeleotris marmoratus; Phoxinus neogaeus; Pristomyrmex punctatus; Pseudobagrus brevicorpus; Seiridium cardinale; Stenopsyche marmorata; Tetranychus evansi and Xerus inauris. These loci were cross-tested on the following species: Agalinis decemloba; Agalinis tenella; Agalinis obtusifolia; Agalinis setacea; Agalinis skinneriana; Cercospora zeina; Cercospora kikuchii; Cercospora sorghi; Mycosphaerella graminicola; Setosphaeria turcica; Magnaporthe oryzae; Cotesia flavipes; Cotesia marginiventris; Grindelia Xpaludosa; Grindelia chiloensis; Grindelia fastigiata; Grindelia lanceolata; Grindelia squarrosa; Leucadendron coniferum; Leucadendron salicifolium; Leucadendron tinctum; Leucadendron meridianum; Laodelphax striatellus; Sogatella furcifera; Phoxinus eos; Phoxinus rigidus; Phoxinus brevispinosus; Phoxinus bicolor; Tetranychus urticae; Tetranychus turkestani; Tetranychus ludeni; Tetranychus neocaledonicus; Tetranychus amicus; Amphitetranychus viennensis; Eotetranychus rubiphilus; Eotetranychus tiliarium; Oligonychus perseae; Panonychus citri; Bryobia rubrioculus; Schizonobia bundi; Petrobia harti; Xerus princeps; Spermophilus tridecemlineatus and Sciurus carolinensis.

13.
Tob Control ; 16 Suppl 1: i81-6, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18048638

RESUMO

Telephone based tobacco cessation services, or quitlines, have become central components of many comprehensive tobacco control programmes. This paper provides an overview of their history, noting milestones in the growth of quitlines. Key factors in their worldwide adoption were solid evidence from clinical trials with large community samples and strong backing from public health officials. Quitlines are now available throughout most of North America, Europe, Australia and in many other locations around the world. The paper also offers several recommendations for future directions in quitline practice and research. Benchmarks should be established for key areas of quitline implementation, such as accessibility, quality and cost efficiency. Advances in pharmacotherapy, telephony and web based applications should be investigated for opportunities to expand service offerings. Research and development are needed to determine how best to serve a diverse clientele in the most cost effective manner. Funding should be expanded and diversified to enable quitlines to serve much larger numbers of users. Healthcare providers should be targeted for quitline promotion, to engage them in a broad effort to increase the number of patients receiving cessation messages from clinicians. The goal of quitline promotion should expand to include an increase in unaided quit attempts in the population. Early research findings were quickly adopted in quitline practice, and future research to answer questions that have arisen through the implementation of quitlines will probably also find quick adoption.


Assuntos
Linhas Diretas/tendências , Abandono do Uso de Tabaco/métodos , Protocolos Clínicos , Aconselhamento/organização & administração , Aconselhamento/tendências , Atenção à Saúde/tendências , Medicina Baseada em Evidências , Linhas Diretas/organização & administração , Humanos
14.
Avian Dis ; 50(3): 463-6, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17039853

RESUMO

A flock of approximately 15,000 ring-necked pheasants (Phasianus colchicus) was evaluated for a sudden increase in mortality and acute neurological signs after having been previously diagnosed 3 wk earlier with a chronic respiratory disease of undetermined etiology. Approximately 25 live birds were displaying neurological signs including circling, ataxia, and obtunded behavior and 50 birds were dead. Three birds with neurological signs were submitted for evaluation. Extensive subcutaneous hemorrhage over the head and penetrating puncture wounds through the skull and into the brain were found. Trauma from a wild predatory mammal, most likely the long-tailed weasel (Mustela frenata) that had invaded the pheasant house and expressed surplus killing behavior was determined to be the cause of the acute neurological signs and mortality. The relationship of the chronic respiratory disease to the predation episode was not determined but it is possible that pheasants with severe respiratory disease may have had increased susceptibility to predation.


Assuntos
Doenças das Aves/etiologia , Doenças das Aves/fisiopatologia , Galliformes/lesões , Mustelidae/fisiologia , Doenças do Sistema Nervoso/veterinária , Comportamento Predatório/fisiologia , Animais , Doenças das Aves/diagnóstico , Feminino , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Pele/lesões , Crânio/lesões
15.
Mitochondrion ; 5(1): 1-13, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16060289

RESUMO

The adenine nucleotide translocase (ANT) is a key component in maintaining cellular energy homeostasis, and has also been implicated in formation of the mitochondrial permeability transition pore. Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line. Overexpression resulted in a concomitant decrease in the endogenous ANT content, allowing for the characterization of binding of known ANT ligands to the human protein. Binding affinities for bongkrekic acid (BKA), ADP, and atractyloside (ATR) were measured in mitochondria from the human ANT-3 expressing cell line, and compared to similar preparations from bovine heart mitochondria by use of a novel radioiodinated derivative of ATR. Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria. Characterizations such as these of human ANT isoforms may lead to drug development for enhanced mitochondrial function and cellular viability.


Assuntos
Translocador 3 do Nucleotídeo Adenina/genética , Translocador 3 do Nucleotídeo Adenina/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Difosfato de Adenosina/metabolismo , Animais , Atractilosídeo/análogos & derivados , Atractilosídeo/química , Atractilosídeo/metabolismo , Ácido Bongcréquico/metabolismo , Bovinos , Linhagem Celular , Metabolismo Energético , Expressão Gênica , Humanos , Técnicas In Vitro , Radioisótopos do Iodo , Cinética , Ligantes , Mitocôndrias Cardíacas/metabolismo , Mariposas , Ligação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
16.
Rehabil Psychol ; 50(4): 325-336, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26321774

RESUMO

OBJECTIVE: To evaluate the feasibility of a telehealth psychoeducation intervention for persons with schizophrenia and their family members. STUDY DESIGN: Randomized controlled trial. PARTICIPANTS: 30 persons with schizophrenia and 21 family members or other informal support persons. INTERVENTIONS: Web-based psychoeducation program that provided online group therapy and education. MAIN OUTCOME MEASURES: Measures for persons with schizophrenia included perceived stress and perceived social support; for family members, they included disease-related distress and perceived social support. RESULTS: At 3 months, participants with schizophrenia in the intervention group reported lower perceived stress (p = .04) and showed a trend for a higher perceived level of social support (p = .06). CONCLUSIONS: The findings demonstrate the feasibility and impact of providing telehealth-based psychosocial treatments, including online therapy groups, to persons with schizophrenia and their families.

17.
MAGMA ; 18(1): 3-6, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15592693

RESUMO

We previously reported cerebellar and putaminal transverse relaxation time (T2) differences in children with ADHD and in adults with childhood trauma. As brain T2 can be altered by deoxyhemoglobin concentration ([dHb]) and because [dHb] is proportional to regional cerebral blood volume (rCBV), at steady state we attributed those differences to rCBV changes. Studies in other species have established a correlation between T2 and rCBV; however this has yet to be demonstrated in human brain. Echo planar imaging (EPI) T2 relaxometry and dynamic susceptibility-contrast (DSC) MRI were used to measure T2 and rCBV in 11 healthy adults. Significant T2-rCBV correlations were observed in both cerebellar vermis and putamen (r = 0.759,p = 0.007;r = 0.782,p = 0.004, respectively). These correlations predict 9 +/- 3% and 10 +/- 3% rCBV changes, respectively, for each 1-msec change in T2. Consequently, brain T2 measurements may be useful for estimating steady-state rCBV.


Assuntos
Cerebelo/irrigação sanguínea , Cerebelo/fisiologia , Circulação Cerebrovascular/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Putamen/irrigação sanguínea , Putamen/fisiologia , Adolescente , Adulto , Volume Sanguíneo/fisiologia , Encéfalo/irrigação sanguínea , Encéfalo/fisiologia , Meios de Contraste , Feminino , Humanos , Masculino , Estatística como Assunto
18.
Pediatr Crit Care Med ; 5(4): 384-90, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15215011

RESUMO

OBJECTIVE: To evaluate whether hemoglobin-based oxygen-carrying solution (HBOC)-201 (Biopure) is an effective alternative to donor blood for extracorporeal membrane oxygenation support in a porcine model of acute respiratory distress syndrome (ARDS). DESIGN: Randomized animal clinical trial. SETTING: Animal surgical research laboratory. SUBJECTS: Immature Yorkshire swine were assigned to one of three groups: 1, noninjured animals, donor porcine blood primed circuit; 2, ARDS-injured, HBOC-201 primed circuit; or 3, ARDS-injured, donor blood primed. INTERVENTIONS: ARDS injury was induced in groups 2 and 3 with oleic acid infusion before bypass. All animals were placed on full venoarterial extracorporeal membrane oxygenation support for 8 hrs. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and laboratory samples were measured at baseline and hourly for 8 hrs. Data analysis consisted of repeated-measures analysis of variance with post hoc analysis. We found that 100% of animals survived on extracorporeal membrane oxygenation for the duration of the study period. HBOC-supported animals had comparable oxygen delivery to both donor blood groups. Mean pulmonary artery pressure, heart rate, and lactate concentrations were higher in the injury groups. Blood pressure was mildly increased in HBOC animals (p <.05 vs. control animals). Methemoglobin concentrations in the HBOC group were elevated and increased over time on extracorporeal membrane oxygenation (p <.001). CONCLUSIONS: HBOC-201 appears to be an effective alternative circuit-priming agent for use during extracorporeal membrane oxygenation. HBOC offers the advantages of rapid availability and diminished donor blood cell exposure. The efficacy of HBOC in longer duration bypass, and its associated methemoglobinemia, need to be further investigated.


Assuntos
Substitutos Sanguíneos/administração & dosagem , Oxigenação por Membrana Extracorpórea/métodos , Síndrome do Desconforto Respiratório/terapia , Análise de Variância , Animais , Hemoglobinas , Distribuição Aleatória , Suínos
19.
Vision Res ; 44(9): 903-13, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14992834

RESUMO

The responses of motion mechanisms depend not only on the direction of a stimulus, but also on its contrast, coherence and speed. We examined how contrast, coherence and directional selectivity interact by measuring directional tuning psychophysically across a wide range of coherence and contrast levels. We fit data with a simple model that estimated directional tuning bandwidth using contrast and coherence gain parameters that were based on neurophysiological estimates. This model estimated a bandwidth of approximately 90 degrees for directionally selective mechanisms. Bandwidth was invariant across a wide range of contrasts and coherences, as predicted by models of contrast normalization.


Assuntos
Sensibilidades de Contraste/fisiologia , Modelos Psicológicos , Percepção de Movimento/fisiologia , Humanos , Neurofisiologia , Psicofísica
20.
J Neurochem ; 79(6): 1207-16, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11752061

RESUMO

Na(+)-dependent excitatory amino acid transporters (EAATs) normally function to remove extracellular glutamate from brain extracellular space, but EAATs can also increase extracellular glutamate by reversal of uptake. Effects of inhibitors on EAATs can be complex, depending on cell type, whether conditions favor glutamate uptake or uptake reversal and whether the inhibitor itself is a substrate for the transporters. The present study assessed EAAT inhibitors for their ability to inhibit glutamate uptake, act as transporter substrates and block uptake reversal in astrocyte and neuron cultures. L-threo-beta-hydroxyaspartate (L-TBHA), DL-threo-beta-benzyloxyaspartate (DL-TBOA), L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC) (+/-)-cis-4-methy-trans-pyrrolidine-2,4-dicarboxylic acid (cis-4-methy-trans-2,4-PDC) and L-antiendo-3,4-methanopyrrolidine-2,4-dicarboxylic acid (L-antiendo-3,4-MPDC) inhibited L-[14C]glutamate uptake in astrocytes with equilibrium binding constants ranging from 17 microM (DL-TBOA and L-TBHA) - 43 microM (cis-4-methy-trans-2,4-PDC). Transportability of inhibitors was assessed in astrocytes and neurons. While L-TBHA, L-trans-2,4-PDC, cis-4-methy-trans-2,4-PDC and L-antiendo-3,4-MPDC displayed significant transporter substrate activities in neurons and astrocytes, DL-TBOA was a substrate only in astrocytes. This effect of DL-TBOA was concentration-dependent, leading to complex effects on glutamate uptake reversal. At concentrations low enough to produce minimal DL-TBOA uptake velocity (< or = 10 microM), DL-TBOA blocked uptake reversal in ATP-depleted astrocytes; this blockade was negated at concentrations that drove substantial DL-TBOA uptake (> 10 microM). These findings indicate that the net effects of EAAT inhibitors can vary with cell type and exposure conditions.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Ácido Aspártico/farmacologia , Astrócitos/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Ácidos Dicarboxílicos/farmacologia , Ácido Glutâmico/metabolismo , Ácido Caínico/análogos & derivados , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Pirrolidinas/farmacologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Trifosfato de Adenosina/análise , Sistema X-AG de Transporte de Aminoácidos/antagonistas & inibidores , Animais , Ácido Aspártico/análogos & derivados , Astrócitos/metabolismo , Transporte Biológico/efeitos dos fármacos , Proteínas de Transporte/antagonistas & inibidores , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Ácido Glutâmico/farmacologia , Ácido Caínico/farmacologia , Camundongos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Neurônios/metabolismo , Prosencéfalo/citologia , Especificidade por Substrato
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