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PURPOSE: Our aim was to develop a high-quality, mobile cone-beam computed tomography (CBCT) scanner for point-of-care detection and monitoring of low-contrast, soft-tissue abnormalities in the head/brain, such as acute intracranial hemorrhage (ICH). This work presents an integrated framework of hardware and algorithmic advances for improving soft-tissue contrast resolution and evaluation of its technical performance with human subjects. METHODS: Four configurations of a CBCT scanner prototype were designed and implemented to investigate key aspects of hardware (including system geometry, antiscatter grid, bowtie filter) and technique protocols. An integrated software pipeline (c.f., a serial cascade of algorithms) was developed for artifact correction (image lag, glare, beam hardening and x-ray scatter), motion compensation, and three-dimensional image (3D) reconstruction [penalized weighted least squares (PWLS), with a hardware-specific statistical noise model]. The PWLS method was extended in this work to accommodate multiple, independently moving regions with different resolution (to address both motion compensation and image truncation). Imaging performance was evaluated quantitatively and qualitatively with 41 human subjects in the neurosciences critical care unit (NCCU) at our institution. RESULTS: The progression of four scanner configurations exhibited systematic improvement in the quality of raw data by variations in system geometry (source-detector distance), antiscatter grid, and bowtie filter. Quantitative assessment of CBCT images in 41 subjects demonstrated: ~70% reduction in image nonuniformity with artifact correction methods (lag, glare, beam hardening, and scatter); ~40% reduction in motion-induced streak artifacts via the multi-motion compensation method; and ~15% improvement in soft-tissue contrast-to-noise ratio (CNR) for PWLS compared to filtered backprojection (FBP) at matched resolution. Each of these components was important to improve contrast resolution for point-of-care cranial imaging. CONCLUSIONS: This work presents the first application of a high-quality, point-of-care CBCT system for imaging of the head/ brain in a neurological critical care setting. Hardware configuration iterations and an integrated software pipeline for artifacts correction and PWLS reconstruction mitigated artifacts and noise to achieve image quality that could be valuable for point-of-care detection and monitoring of a variety of intracranial abnormalities, including ICH and hydrocephalus.
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Tomografia Computadorizada de Feixe Cônico , Cabeça , Algoritmos , Artefatos , Encéfalo/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imagens de FantasmasRESUMO
Effects of species diversity on population and community stability (or more precisely, the effects of species richness on temporal variability) have been studied for several decades, but there have been no large-scale tests in natural communities of predictions from theory. We used 91 data sets including plants, fish, small mammals, zooplankton, birds, and insects, to examine the relationship between species richness and temporal variability in populations and communities. Seventy-eight of 91 data sets showed a negative relationship between species richness and population variability; 46 of these relationships were statistically significant. Only five of the 13 positive richness-population variability relationships were statistically significant. Similarly, 51 of 91 data sets showed a negative relationship between species richness and community variability; of these, 26 were statistically significant. Seven of the 40 positive richness-community-variability relationships were statistically significant. We were able to test transferability (i.e., the predictive ability of models for sites that are spatially distinct from sites that were used to build the models) for 69 of 91 data sets; 35 and 31 data sets were transferable at the population and community levels, respectively. Only four were positive at the population level, and two at the community level. We conclude that there is compelling evidence of a negative relationship between species richness and temporal variability for about one-half of the ecological communities we examined. However, species richness explained relatively little of the variability in population or community abundances and resulted in small improvements in predictive ability.
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Biodiversidade , Ecossistema , Animais , Plantas , Dinâmica Populacional , ZooplânctonRESUMO
A neurocatastrophe or severe brain injury (SBI) is a central nervous system insult associated with a high likelihood of death or severe disability. While many etiologic processes may lead to SBI, the most common and best-studied clinical paradigms are traumatic brain injury and anoxic-ischemic encephalopathy following cardiac arrest. Clinical phenotypes following SBI include acute and chronic disorders of consciousness as well as a range of cognitive and behavioral impairments. A fundamental task for medical teams working in the acute phase is to estimate SBI recovery probabilities with the highest degree of accuracy possible. Predictions made on the basis of single features or variables lack discrimination and are generally supplanted by multivariable models that combine clinical, imaging, and laboratory data into tractable scoring systems. Yet existing scores fail to classify outcomes with the accuracy that would support individual patient-level decision making. Improved prognostication will likely depend on the use of molecular and imaging data that capture unique biologic features in individual patients with SBI. The integration of these additional layers of information will require iterative computational approaches.
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Lesões Encefálicas/complicações , Humanos , PrognósticoRESUMO
BACKGROUND: Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours. PATIENTS AND METHODS: Paired peripheral blood samples were obtained from 44 patients with solid tumours receiving cytotoxic therapy and synthetic erythropoietin (usual care; n=21) or usual care plus supervised aerobic training (n=23) for 12 weeks. Samples were characterised for changes in immune, cytokine and angiogenic factors, and metabolic intermediates. Aerobic training consisted of three supervised cycle ergometry sessions per week at 60% to 100% of peak oxygen consumption (VO2peak), 30-45 min per session, for 12 weeks following a nonlinear prescription. RESULTS: The between-group delta change in cardiopulmonary function was +4.1 ml kg (-1) min(-1), favouring aerobic training (P<0.05). Significant pre-post between-group differences for five cytokine and angiogenic factors (HGF, IL-4, macrophage inflammatory protein-1ß (MIP-1ß), vascular endothelial growth factor (VEGF), and TNF-α) also favour the aerobic training group (P's<0.05). These reductions occurred in conjunction with nonsignificant group differences for T lymphocytes CD4(+), CD8(+), and CD8(+)/CD45RA (P<0.10). For these factors, circulating concentrations generally increased from baseline to week 12 in the aerobic training group compared with decreases or no change in the usual care group. No significant changes in any metabolic intermediates were observed. CONCLUSIONS: Aerobic training alters host availability of select immune-inflammatory effectors in patients with solid tumours; larger confirmatory studies in more homogenous samples are warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Eritropoetina/administração & dosagem , Terapia por Exercício/métodos , Neoplasias/terapia , Fenômenos Fisiológicos Cardiovasculares , Ensaios Clínicos como Assunto , Terapia Combinada , Eritropoetina/uso terapêutico , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Consumo de Oxigênio , Projetos PilotoAssuntos
Anestesiologia , Cuidados Críticos , Neurologia , Sociedades Médicas , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Dano Encefálico Crônico/terapia , Lesões Encefálicas/terapia , Transtornos da Consciência/diagnóstico , Transtornos da Consciência/etiologia , Transtornos da Consciência/prevenção & controle , França , Humanos , Monitorização Neurofisiológica Intraoperatória , Prognóstico , Assistência TerminalRESUMO
BACKGROUND AND PURPOSE: Extensive white matter damage has been documented in patients with severe traumatic brain injury, yet how this damage evolves in the long term is not well understood. We used DTI to study white matter changes at 5 years after traumatic brain injury. MATERIALS AND METHODS: There were 8 healthy control participants and 13 patients with severe traumatic brain injury who were enrolled in a prospective observational study, which included clinical assessment and brain MR imaging in the acute setting (< 6 weeks) and 2 years and 5 years after injury. Only subjects with mild to moderate disability or no disability at 1 year were included in this analysis. DTI parameters were measured in 20 different brain regions and were normalized to values obtained in an age-matched control group. RESULTS: In the acute setting, fractional anisotropy was significantly lower in the genu and body of the corpus callosum and in the bilateral corona radiata in patients compared with control participants, whereas radial diffusivity was significantly (P < .05) higher in these tracts. At 2 years, fractional anisotropy in these tracts had further decreased and radial diffusivity had increased. No significant changes were detected between 2 and 5 years after injury. The baseline radial diffusivity and fractional anisotropy values in the anterior aspect of the brain stem, genu and body of the corpus callosum, and the right and left corona radiata were significantly (P < .05) associated with neurocognitive sequelae (including amnesia, aphasia, and dyspraxia) at year 5. CONCLUSIONS: DTI changes in major white matter tracts persist up to 5 years after severe traumatic brain injury and are most pronounced in the corpus callosum and corona radiata. Limited structural change is noted in the interval between 2 and 5 years.
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Lesões Encefálicas/patologia , Encéfalo/patologia , Fibras Nervosas Mielinizadas/patologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índices de Gravidade do Trauma , Adulto JovemRESUMO
AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, ß-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost ≥4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (∆HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). RESULTS: Mean weight loss was 8.67 ± 4.28 kg; mean ∆HOMA-IR was -0.80 ± 1.73, range -28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with ∆HOMA-IR (p < 0.0001). ∆HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ∆HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ∆HOMA-IR (p = 0.007). CONCLUSIONS/INTERPRETATION: A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.
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Aminoácidos de Cadeia Ramificada/química , Resistência à Insulina , Adulto , Algoritmos , Aminoácidos/química , Biomarcadores/metabolismo , Índice de Massa Corporal , Peso Corporal , Estudos de Coortes , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Análise de Componente Principal , Redução de PesoRESUMO
AIMS/HYPOTHESIS: Insulin resistance (IR) is associated with obesity, but can also develop in individuals with normal body weight. We employed comprehensive profiling methods to identify metabolic events associated with IR, while controlling for obesity. METHODS: We selected 263 non-obese (BMI approximately 24 kg/m2) Asian-Indian and Chinese men from a large cross-sectional study carried out in Singapore. Individuals taking medication for diabetes or hyperlipidaemia were excluded. Participants were separated into lower and upper tertiles of IR based on HOMA indices of < or =1.06 or > or =1.93, respectively. MS-based metabolic profiling of acylcarnitines, amino acids and organic acids was combined with hormonal and cytokine profiling in all participants. RESULTS: After controlling for BMI, commonly accepted risk factors for IR, including circulating fatty acids and inflammatory cytokines, did not discriminate the upper and lower quartiles of insulin sensitivity in either Asian- Indian or Chinese men. Instead, IR was correlated with increased levels of alanine, proline, valine, leucine/isoleucine, phenylalanine, tyrosine, glutamate/glutamine and ornithine, and a cluster of branched-chain and related amino acids identified by principal components analysis. These changes were not due to increased protein intake by individuals in the upper quartile of IR. Increased abdominal adiposity and leptin, and decreased adiponectin and IGF-binding protein 1 were also correlated with IR. CONCLUSIONS/INTERPRETATION: These findings demonstrate that perturbations in amino acid homeostasis, but not inflammatory markers or NEFAs, are associated with IR in individuals of relatively low body mass.
Assuntos
Índice de Massa Corporal , Resistência à Insulina/fisiologia , Adiponectina/sangue , Adulto , Aminoácidos/sangue , Aminoácidos/metabolismo , Povo Asiático , Glicemia/metabolismo , Colesterol/sangue , Estudos Transversais , Demografia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Índia , Insulina/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Interleucinas/sangue , Estilo de Vida , Lipídeos/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Seleção de Pacientes , Grupos Raciais , Fatores de Risco , Singapura/epidemiologia , População BrancaRESUMO
OBJECTIVE: To evaluate the role of 23.4% saline in the management of transtentorial herniation (TTH) in patients with supratentorial lesions. METHODS: Consecutive patients with clinically defined TTH treated with 23.4% saline (30 to 60 mL) were included in a retrospective cohort. Factors associated with successful reversal of TTH were determined. RESULTS: Seventy-six TTH events occurred in 68 patients admitted with intracerebral hemorrhage (n = 29), subarachnoid hemorrhage (n = 16), stroke (n = 8), brain tumor (n = 8), subdural hematoma (n = 5), epidural hematoma (n = 1), and meningitis (n = 1). In addition to 23.4% saline, TTH management included hyperventilation (70% of events), mannitol (57%), propofol (62%), pentobarbital (15%), ventriculostomy drainage (27%), and decompressive hemicraniectomy (18%). Reversal of TTH occurred in 57/76 events (75%). Intracranial pressure decreased from 23 +/- 16 mm Hg at the time of TTH to 14 +/- 10 mm Hg at 1 hour (p = 0.002), and 11 +/- 12 mm Hg at 24 hours (p = 0.001) among 22 patients with intracranial pressure monitors. Reversal of TTH was predicted by a >/=5 mmol/L rise in serum sodium concentration (p = 0.001) or an absolute serum sodium of >/=145 mmol/L (p = 0.007) 1 hour after 23.4% saline. Adverse effects included transient hypotension in 13 events (17%); no evidence of central pontine myelinolysis was detected on post-herniation MRI (n = 18). Twenty-two patients (32%) survived to discharge, with severe disability in 17 and mild to moderate disability in 5. CONCLUSION: Treatment with 23.4% saline was associated with rapid reversal of transtentorial herniation (TTH) and reduced intracranial pressure, and had few adverse effects. Outcomes of TTH were poor, but medical reversal may extend the window for adjunctive treatments.
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Edema Encefálico/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Hérnia/tratamento farmacológico , Hipertensão Intracraniana/tratamento farmacológico , Solução Salina Hipertônica/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/fisiopatologia , Edema Encefálico/complicações , Edema Encefálico/fisiopatologia , Neoplasias Encefálicas/complicações , Hemorragia Cerebral/complicações , Estudos de Coortes , Diuréticos Osmóticos/uso terapêutico , Esquema de Medicação , Feminino , Hérnia/etiologia , Hérnia/fisiopatologia , Humanos , Hipertensão Intracraniana/complicações , Hipertensão Intracraniana/fisiopatologia , Pressão Intracraniana/efeitos dos fármacos , Masculino , Manitol/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sódio/sangue , Taxa de Sobrevida , Resultado do Tratamento , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
(my)Grid supports in silico experiments in the life sciences, enabling the design and enactment of workflows as well as providing components to assist service discovery, data and metadata management. The (my)Grid ontology is one component in a larger semantic discovery framework for the identification of the highly distributed and heterogeneous bioinformatics services in the public domain. From an initial model of formal OWL-DL semantics throughout, we now adopt a spectrum of expressivity and reasoning for different tasks in service annotation and discovery. Here, we discuss the development and use of the (my)Grid ontology and our experiences in semantic service discovery.
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Biologia Computacional , Software , Interpretação Estatística de Dados , Bases de Dados Factuais , Internet , SemânticaRESUMO
In population ecology, there has been a fundamental controversy about the relative importance of competition-driven (density-dependent) population regulation vs. abiotic influences such as temperature and precipitation. The same issue arises at the community level; are population sizes driven primarily by changes in the abundances of cooccurring competitors (i.e., compensatory dynamics), or do most species have a common response to environmental factors? Competitive interactions have had a central place in ecological theory, dating back to Gleason, Volterra, Hutchison and MacArthur, and, more recently, Hubbell's influential unified neutral theory of biodiversity and biogeography. If competitive interactions are important in driving year-to-year fluctuations in abundance, then changes in the abundance of one species should generally be accompanied by compensatory changes in the abundances of others. Thus, one necessary consequence of strong compensatory forces is that, on average, species within communities will covary negatively. Here we use measures of community covariance to assess the prevalence of negative covariance in 41 natural communities comprising different taxa at a range of spatial scales. We found that species in natural communities tended to covary positively rather than negatively, the opposite of what would be expected if compensatory dynamics were important. These findings suggest that abiotic factors such as temperature and precipitation are more important than competitive interactions in driving year-to-year fluctuations in species abundance within communities.
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Comportamento Competitivo , Ecossistema , Meio Ambiente , Modelos Teóricos , Dinâmica Populacional , Análise de Variância , AnimaisRESUMO
Biologists were early adopters of the Web and continue to use it as the primary means of delivering data, tools and knowledge to their community. The Web is made by the links between pages, yet these links have many limitations: they are static and maintained by hand; they can only link one lexical item to another single resource; ownership is necessary for the placement of link anchors and the link mechanism is essentially inflexible. Dynamic linking services, supported by ontologies, offer a mechanism to overcome such restrictions. The Conceptual Open Hypermedia Service (COHSE) system enhances web resources through the dynamic addition of hypertext links. These links are derived through the use of an ontology and associated lexicon along with a mapping from concepts to possible link targets. We describe an application of COHSE to Bioinformatics, using the Gene Ontology (GO) as an ontology and associated keyword mappings and GO associations as link targets. The resulting demonstrator (referred to here as GOHSE) provides both glossary functionality and the possibility of building knowledge based hypertext structures linking bioinformatics resources.
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Genes , Vocabulário Controlado , Animais , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , HumanosRESUMO
MOTIVATION: In silico experiments necessitate the virtual organization of people, data, tools and machines. The scientific process also necessitates an awareness of the experience base, both of personal data as well as the wider context of work. The management of all these data and the co-ordination of resources to manage such virtual organizations and the data surrounding them needs significant computational infra-structure support. RESULTS: In this paper, we show that (my)Grid, middleware for the Semantic Grid, enables biologists to perform and manage in silico experiments, then explore and exploit the results of their experiments. We demonstrate (my)Grid in the context of a series of bioinformatics experiments focused on a 1.5 Mb region on chromosome 7 which is deleted in Williams-Beuren syndrome (WBS). Due to the highly repetitive nature of sequence flanking/in the WBS critical region (WBSCR), sequencing of the region is incomplete leaving documented gaps in the released sequence. (my)Grid was used in a series of experiments to find newly sequenced human genomic DNA clones that extended into these 'gap' regions in order to produce a complete and accurate map of the WBSCR. Once placed in this region, these DNA sequences were analysed with a battery of prediction tools in order to locate putative genes and regulatory elements possibly implicated in the disorder. Finally, any genes discovered were submitted to a range of standard bioinformatics tools for their characterization. We report how (my)Grid has been used to create workflows for these in silico experiments, run those workflows regularly and notify the biologist when new DNA and genes are discovered. The (my)Grid services collect and co-ordinate data inputs and outputs for the experiment, as well as much provenance information about the performance of experiments on WBS. AVAILABILITY: The (my)Grid software is available via http://www.mygrid.org.uk
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Algoritmos , Mapeamento Cromossômico/métodos , Predisposição Genética para Doença/genética , Análise de Sequência de DNA/métodos , Software , Interface Usuário-Computador , Síndrome de Williams/genética , Gráficos por Computador , InternetRESUMO
MOTIVATION: Many bioinformatics data resources not only hold data in the form of sequences, but also as annotation. In the majority of cases, annotation is written as scientific natural language: this is suitable for humans, but not particularly useful for machine processing. Ontologies offer a mechanism by which knowledge can be represented in a form capable of such processing. In this paper we investigate the use of ontological annotation to measure the similarities in knowledge content or 'semantic similarity' between entries in a data resource. These allow a bioinformatician to perform a similarity measure over annotation in an analogous manner to those performed over sequences. A measure of semantic similarity for the knowledge component of bioinformatics resources should afford a biologist a new tool in their repertoire of analyses. RESULTS: We present the results from experiments that investigate the validity of using semantic similarity by comparison with sequence similarity. We show a simple extension that enables a semantic search of the knowledge held within sequence databases. AVAILABILITY: Software available from http://www.russet.org.uk.
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Bases de Dados Genéticas , Documentação , Armazenamento e Recuperação da Informação/métodos , Processamento de Linguagem Natural , Proteínas/química , Proteínas/classificação , Análise de Sequência de Proteína/métodos , Terminologia como Assunto , Inteligência Artificial , Bases de Dados Factuais , Perfilação da Expressão Gênica/métodos , Humanos , Filogenia , Proteínas/genética , Reprodutibilidade dos Testes , Semântica , Sensibilidade e Especificidade , Alinhamento de Sequência , Estatística como AssuntoRESUMO
Many bioinformatics resources hold data in the form of sequences. Often this sequence data is associated with a large amount of annotation. In many cases this data has been hard to model, and has been represented as scientific natural language, which is not readily computationally amenable. The development of the Gene Ontology provides us with a more accessible representation of some of this data. However it is not clear how this data can best be searched, or queried. Recently we have adapted information content based measures for use with the Gene Ontology (GO). In this paper we present detailed investigation of the properties of these measures, and examine various properties of GO, which may have implications for its future design.
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Biologia Computacional , Genômica/estatística & dados numéricos , Classificação , Bases de Dados de Proteínas , Humanos , Proteômica/estatística & dados numéricos , Alinhamento de Sequência/estatística & dados numéricosRESUMO
Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon-chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated by electrospray ionization mass spectrometry (ESI-MS). Information was obtained relevant to the structure and the speciation of various Fe(III)-dihydroxamate complexes present in aqueous solution by (1) comparing different ionization techniques (ESI and FAB), (2) altering the experimental parameters (Fe3+/ligand ratio, pH, cone voltage), (3) using high-stability hexacoordinated Fe(III) siderophore complex mixtures (ferrioxamine B/ferrioxamine E) as a calibrant to quantify intrinsically neutral (H+ clustered or protonated) and intrinsically charged complexes, and (4) using mixed-metal complexes containing Fe3+, Ga3+, and Al3+. These results illustrate that for all dihydroxamic acid ligands investigated multiple tris- and bis-chelated mono- and di-Fe(III) species are present in relative concentrations that depend on the pH and Fe/L ratio.
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Ácidos Hidroxâmicos , Ferro , Piperazinas/química , Sideróforos/química , Calibragem , Modelos Moleculares , Conformação Molecular , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-AtividadeRESUMO
A manganese(III) complex of biliverdin IX dimethyl ester, (MnIIIBVDME)2, was prepared and characterized by elemental analysis, UV/vis spectroscopy, cyclic voltammetry, chronocoulometry, electrospray mass spectrometry, freezing-point depression, magnetic susceptibility, and catalytic dismuting of superoxide anion (O2.-). In a dimeric conformation each trivalent manganese is bound to four pyrrolic nitrogens of one biliverdin dimethyl ester molecule and to the enolic oxygen of another molecule. This type of coordination stabilizes the +4 metal oxidation state, whereby the +3/+4 redox cycling of the manganese in aqueous medium was found to be at E1/2 = +0.45 V vs NHE. This potential allows the Mn(III)/Mn(IV) couple to efficiently catalyze the dismutation of O2.- with the catalytic rate constant of kcat = 5.0 x 10(7) M-1 s-1 (concentration calculated per manganese) obtained by cytochrome c assay at pH 7.8 and 25 degrees C. The fifth coordination site of the manganese is occupied by an enolic oxygen, which precludes binding of NO., thus enhancing the specificity of the metal center toward O2.-. For the same reason the (MnIIIBVDME)2 is resistant to attack by H2O2. The compound also proved to be an efficient SOD mimic in vivo, facilitating the aerobic growth of SOD-deficient Escherichia coli.
Assuntos
Biliverdina/análogos & derivados , Biliverdina/química , Manganês/química , Superóxidos/química , Catálise , Grupo dos Citocromos c/metabolismo , Eletroquímica , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Peróxido de Hidrogênio/química , Magnetismo , Estrutura Molecular , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Oxirredução , Radiólise de Impulso , Espectrometria de Massas por Ionização por Electrospray , Análise Espectral , Superóxido Dismutase/química , Superóxido Dismutase/metabolismoRESUMO
The neuromuscular disorders are associated with diminished cardiopulmonary reserves, deficient airway protection mechanisms, and atypical responses to drugs used during anesthesia. Many of these conditions are uncommon, and methodologically sound evidence to guide clinical practice is limited. The disorders discussed in the present review are the motor neuron diseases, peripheral neuropathies, myasthenic syndromes, and myopathies, including malignant hyperthermia. Recent data on pathogenesis and medical management are outlined, as are studies relating to anesthesia and the perioperative period.
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BACKGROUND: The usefulness of peripheral nerve blockade in the anesthetic management of hip surgery has not been clearly established. Because sensory afferents from the hip include several branches of the lumbar plexus, the authors hypothesized that a lumbar plexus block could reduce pain from a major hip procedure. METHODS: In a double-blind prospective trial, 60 patients undergoing total hip arthroplasty were randomized to receive general anesthesia with (plexus group, n = 30) or without (control group, n = 30) a posterior lumbar plexus block. The block was performed after induction using a nerve stimulator, and 0.4 ml/kg bupivacaine, 0.5%, with epinephrine was injected. General anesthesia was standardized, and supplemental fentanyl was administered per hemodynamic guidelines. Postoperative pain and patient-controlled intravenous morphine use were serially assessed for 48 h. RESULTS: The proportion of patients receiving supplemental fentanyl intraoperatively was more than 3 times greater in the control group (20 of 30 vs. 6 of 29, P = 0.001). In the postanesthesia care unit, a greater than fourfold reduction in pain scores was observed in the plexus group (visual analogue scale [VAS] pain score at arrival 1.3 +/- 2 vs. 5.6 +/- 3, P < 0.001), and "rescue" morphine boluses (administered if VAS > 3) were administered 10 times less frequently (in 2 of 28 vs. in 22 of 29 patients, P < 0.0001). Pain scores and morphine consumption remained significantly lower in the plexus group until 6 h after randomization (VAS at 6 h, 1.4 +/- 1.3 vs. 2.4 +/- 1.4, P = 0.007; cumulative morphine at 6 h, 5.6 +/- 4.7 vs. 12.6 +/- 7.5 mg, P < 0.0001). Operative and postoperative (48 h) blood loss was modestly decreased in the treated group. Epidural-like distribution of anesthesia occurred in 3 of 28 plexus group patients, but no other side-effects were noted. CONCLUSIONS: Posterior lumbar plexus block provides effective analgesia for total hip arthroplasty, reducing intra- and postoperative opioid requirements. Moreover, blood loss during and after the procedure is diminished. Epidural anesthetic distribution should be anticipated in a minority of cases.