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This analysis investigates the cost of carbon capture from the US natural gas-fired electricity generating fleet comparing two technologies: postcombustion capture and direct air capture (DAC). Many of the existing natural gas combined cycle (NGCC) units are suitable for postcombustion capture. We estimated the cost of postcombustion retrofits and investigated the most important unit characteristics contributing to this cost. Units larger than 400 MW, younger than 14 years, more efficient than 45%, and with a utilization (capacity factor) higher than 0.5 were found to be the most promising for retrofit. Counterintuitively, DAC (which is usually not considered for point-source capture) may be cheaper in addressing emissions from nonretrofittable NGCC units. DAC can also address the residual emissions from retrofitted units. Moreover, the economic challenges of postcombustion capture for small natural gas-fired units with low utilization, such as gas turbines, make DAC look favorable for these units. After considering the cost of postcombustion capture for the entire natural gas-related emissions and incorporating the impact of learning-by-doing for both carbon capture technologies, our results show that DAC is the cheaper capture solution for at least 1/3 of all emissions.
Assuntos
Gás Natural , Centrais Elétricas , Dióxido de Carbono/análise , Carvão Mineral , EletricidadeRESUMO
Semaglutide, a glucagon-like peptide 1 (GLP-1) analog, induces weight loss, lowers glucose levels, and reduces cardiovascular risk in patients with diabetes. Mechanistic preclinical studies suggest weight loss is mediated through GLP-1 receptors (GLP-1Rs) in the brain. The findings presented here show that semaglutide modulated food preference, reduced food intake, and caused weight loss without decreasing energy expenditure. Semaglutide directly accessed the brainstem, septal nucleus, and hypothalamus but did not cross the blood-brain barrier; it interacted with the brain through the circumventricular organs and several select sites adjacent to the ventricles. Semaglutide induced central c-Fos activation in 10 brain areas, including hindbrain areas directly targeted by semaglutide, and secondary areas without direct GLP-1R interaction, such as the lateral parabrachial nucleus. Automated analysis of semaglutide access, c-Fos activity, GLP-1R distribution, and brain connectivity revealed that activation may involve meal termination controlled by neurons in the lateral parabrachial nucleus. Transcriptomic analysis of microdissected brain areas from semaglutide-treated rats showed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in the area postrema. We suggest semaglutide lowers body weight by direct interaction with diverse GLP-1R populations and by directly and indirectly affecting the activity of neural pathways involved in food intake, reward, and energy expenditure.
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Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/farmacologia , Vias Neurais/efeitos dos fármacos , Animais , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/efeitos dos fármacos , Camundongos , RatosRESUMO
TNF-blockade has shown clear therapeutic value in rheumatoid arthritis and other immune-mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF-blockade on CD4+ T cell activation, maturation, and proliferation, and assessed whether TNF-inhibitors confer regulatory potential to CD4+ T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4+ T cells with the anti-TNF monoclonal antibody adalimumab promoted IL-10 expression in CD4+ T cells, whilst decreasing cellular activation. In line with this, analysis of gene expression profiling datasets of anti-TNF-treated IL-17 or IFN-γ-producing CD4+ T cells revealed changes in multiple pathways associated with cell cycle and proliferation. Kinetics experiments showed that anti-TNF treatment led to delayed, rather than impaired T-cell activation and maturation. Whilst anti-TNF-treated CD4+ T cells displayed some hyporesponsiveness upon restimulation, they did not acquire enhanced capacity to suppress T-cell responses or modulate monocyte phenotype. These cells however displayed a reduced ability to induce IL-6 and IL-8 production by synovial fibroblasts. Together, these data indicate that anti-TNF treatment delays human CD4+ T-cell activation, maturation, and proliferation, and this reduced activation state may impair their ability to activate stromal cells.
Assuntos
Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Anergia Clonal/efeitos dos fármacos , Anergia Clonal/imunologia , Humanos , Ativação Linfocitária/imunologia , Fenótipo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Programmed death-1 (PD-1) has a pivotal role in the attenuation of adaptive immune responses and peripheral tolerance. Here we describe the identification of the Pekin duck programmed death-1 orthologue (duPD-1). The duPD-1 cDNA encodes a 283-amino acid polypeptide that has an amino acid identity of 70%, 32% and 31% with chicken, murine and human PD-1, respectively. The duck PD-1 gene shares five conserved exons with chicken, murine and human PD-1 genes. A cluster of putative regulatory elements within the conserved region B (CR-B) of the basal promotor is conserved. Homology modeling was most compatible with the two ß-sheet IgV domain structure of murine PD-1. Contact residues, shown to be critical for binding of the respective human and murine PD-1 ligands are mostly conserved between avian and mammalian species, whereas residues that define the cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) are highly conserved across higher vertebrates and frog. Constitutive expression of duPD-1 transcripts was predominantly found in lymphocyte-rich tissues, and mitogen-stimulation of duck peripheral blood mononuclear cells transiently increased duPD-1 mRNA expression. A soluble duPD-1 protein was expressed and shown to engage the identified duck PD-1 ligands. Our observations show considerable evolutionary conservation between mammalian and avian PD-1 orthologues. This work will facilitate further investigation of the role of PD-1 signaling in adaptive immunity in the Pekin duck, a non-mammalian vertebrate and pathogen host with relevance for human and animal health.
Assuntos
Proteínas Aviárias/química , Proteínas Aviárias/genética , Receptor de Morte Celular Programada 1/química , Receptor de Morte Celular Programada 1/genética , Animais , Proteínas Aviárias/classificação , Mapeamento Cromossômico , Clonagem Molecular , Patos , Expressão Gênica , Ligantes , Modelos Moleculares , Filogenia , Receptor de Morte Celular Programada 1/classificação , Receptor de Morte Celular Programada 1/metabolismo , Domínios Proteicos , Estrutura Secundária de Proteína , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Análise de Sequência de Proteína , Distribuição TecidualRESUMO
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide reduce cardiovascular risk in type 2 diabetes patients. The mode of action is suggested to occur through modified atherosclerotic progression. In this study, both of the compounds significantly attenuated plaque lesion development in apolipoprotein E-deficient (ApoE-/-) mice and low-density lipoprotein receptor-deficient (LDLr-/-) mice. This attenuation was partly independent of weight and cholesterol lowering. In aortic tissue, exposure to a Western diet alters expression of genes in pathways relevant to the pathogenesis of atherosclerosis, including leukocyte recruitment, leukocyte rolling, adhesion/extravasation, cholesterol metabolism, lipid-mediated signaling, extracellular matrix protein turnover, and plaque hemorrhage. Treatment with semaglutide significantly reversed these changes. These data suggest GLP-1RAs affect atherosclerosis through an anti-inflammatory mechanism.
RESUMO
This study describes suppurative infectious diseases of the central nervous system (CNS) in domestic ruminants of southern Brazil. Reports from 3.274 cattle, 596 sheep and 391 goats were reviewed, of which 219 cattle, 21 sheep and 7 goats were diagnosed with central nervous system inflammatory diseases. Suppurative infectious diseases of the CNS corresponded to 54 cases (28 cattle, 19 sheep and 7 goats). The conditions observed consisted of listerial meningoencephalitis (8 sheep, 5 goats and 4 cattle), suppurative leptomeningitis and meningoencephalitis (14 cattle, 2 goats and 1 sheep), cerebral (6 cattle and 2 sheep), and spinal cord (7 sheep) abscesses, and basilar empyema (4 cattle and 1 sheep). Bacterial culture identified Listeria monocytogenes (9/54 cases), Escherichia coli (7/54 cases), Trueperella pyogenes (6/54 cases) and Proteus mirabilis (1/54 cases). All cases diagnosed as listeriosis through histopathology yielded positive immunostaining on immunohistochemistry, while 12/17 of the cases of suppurative leptomeningitis and meningoencephalitis presented positive immunostaining for Escherichia coli. Meningoencephalitis by L. monocytogenes was the main neurological disease in sheep and goats, followed by spinal cord abscesses in sheep. In cattle, leptomeningitis and suppurative meningoencephalitis was the most frequent neurological disease for the species, and E. coli was the main cause of these lesions. Basilar empyema, mainly diagnosed in cattle, is related to traumatic injuries, mainly in the nasal cavity, and the main etiologic agent was T. pyogenes.(AU)
Neste trabalho são descritas as doenças neurológicas infecciosas supurativas de ruminantes domésticos na Região Sul do Brasil. Foram avaliados laudos de 3.274 bovinos, 596 ovinos e 391 caprinos, dos quais 219 bovinos, 21 ovinos e sete caprinos foram diagnosticados como doenças inflamatórias no sistema nervoso central. As doenças neurológicas infecciosas supurativas corresponderam a 54 casos (28 bovinos, 19 ovinos e sete caprinos). As enfermidades observadas foram meningoencefalite por Listeria monocytogenes (oito ovinos, cinco caprinos e quatro bovinos), leptomeningite e meningoencefalite supurativa (14 bovinos, dois caprinos e um ovino), abscessos cerebrais (seis bovinos e dois ovinos) e medulares (sete ovinos); e empiema basilar (quatro bovinos e um ovino). Através do isolamento bacteriano foram identificados: L. monocytogenes (9/54 casos), Echerichia coli (7/54 casos), Trueperella pyogenes (6/54 casos) e Proteus mirabilis (1/54 casos). Todos os casos diagnosticados como listeriose por histologia foram positivos na imuno-histoquímica para L. monocytogenes, e 12/17 casos de leptomeningite e meningoencefalite supurativa foram positivos na imuno-histoquímica para E. coli. A meningoencefalite por L. monocytogenes representou a principal enfermidade neurológica em ovinos e caprinos, seguido dos abscessos medulares em ovinos. A leptomeningite e meningoencefalite supurativa foi a doença neurológica supurativa mais frequente em bovinos e o principal agente causador da lesão foi E. coli. O empiema basilar, frequentemente, diagnosticado em bovinos, foi relacionado com lesões traumáticas, principalmente, de cavidade nasal e o principal agente causador foi T. pyogenes.(AU)
Assuntos
Animais , Bovinos , Ruminantes , Abscesso Encefálico/veterinária , Ovinos , Meningite/veterinária , Meningoencefalite/veterinária , Doenças do Sistema Nervoso/veterinária , Supuração/veterináriaRESUMO
Monocytes and macrophages are key mediators of inflammation in rheumatoid arthritis (RA). Their persistence at the inflammatory site is likely to contribute to immunopathology. We sought to characterise one mechanism by which persistence may be achieved: resistance to apoptosis and the role of mir-155 in this process. CD14+ monocytes from peripheral blood (PBM) and synovial fluid (SFM) of RA patients were found to be resistant to spontaneous apoptosis relative to PBM from healthy control (HC) individuals. RA SFM were also resistant to anti-Fas-mediated apoptosis and displayed a gene expression profile distinct from HC and RA PBM populations. Gene expression profiling analysis revealed that the differentially expressed genes in RA SFM vs. PBM were enriched for apoptosis-related genes and showed increased expression of the mir-155 precursor BIC. Following identification of potential mir-155 target transcripts by bioinformatic methods, we show increased levels of mature mir-155 expression in RA PBM and SFM vs. HC PBM and a corresponding decrease in SFM of two predicted mir-155-target mRNAs, apoptosis mediators CASP10 and APAF1. Using miR mimics, we demonstrate that mir-155 over-expression in healthy CD14+ cells conferred resistance to spontaneous apoptosis, but not Fas-induced death in these cells, and resulted in increased production of cytokines and chemokines. Collectively our data indicate that CD14+ cells from patients with RA show enhanced resistance to apoptosis, and suggest that an increase in mir-155 may partially contribute to this phenotype.
Assuntos
Apoptose/genética , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , MicroRNAs/genética , Monócitos/imunologia , Monócitos/metabolismo , Artrite Reumatoide/metabolismo , Biomarcadores , Estudos de Casos e Controles , Sobrevivência Celular/genética , Biologia Computacional/métodos , Citocinas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Fenótipo , Interferência de RNA , Receptor fas/metabolismoRESUMO
OBJECTIVE: Conflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA. METHODS: Using a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127(low) Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte-derived cytokine/chemokine production, and gene expression profiles. RESULTS: No differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin-17 [IL-17], interferon-γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL-1ß, IL-1 receptor antagonist, IL-7, CCL3, or CCL4) by autologous lipopolysaccharide-activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL-6, IL-8, IL-12, IL-15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls. CONCLUSION: Our findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.
Assuntos
Artrite Reumatoide/imunologia , Citocinas/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Antígenos CD4/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-17/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-7/imunologia , Antígenos Comuns de Leucócito/imunologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
INTRODUCTION: Routine cognitive screening for in-patients aged ≥75 years is recommended, but there is uncertainty around how this should be operationalised. We therefore determined the feasibility and reliability of the Abbreviated mental test score (AMTS/10) and its relationship to subjective memory complaint, Montreal Cognitive Assessment (MoCA/30) and informant report in unselected older admissions. METHODS: Consecutive acute general medicine patients aged ≥75 years admitted over 10 weeks (March-May 2013) had AMTS and a question regarding subjective memory complaint (if no known dementia/delirium). At ≥72 h, the 30-point Montreal Cognitive Assessment (MoCA) and Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were done. Cognitive impairment was defined as AMTS < 9 or MoCA < 26 (mild impairment) and MoCA < 20 (moderate/severe impairment) or IQCODE ≥ 3.6. RESULTS: Among 264 patients (mean age/SD = 84.3/5.6 years, 117 (44%) male), 228 (86%) were testable with AMTS. 49/50 (98%) testable patients with dementia/delirium had low AMTS compared with 79/199 (44%) of those without (P < 0.001). Subjective memory complaint agreed poorly with objective cognitive deficit (39% denying a memory problem had AMTS < 9 (kappa = 0.134, P = 0.086)) as did informant report (kappa = 0.18, P = 0.15). In contrast, correlation between AMTS and MoCA was strong (R2 = 0.59, P < 0.001) with good agreement between AMTS < 9 and MoCA < 20 (kappa = 0.50, P < 0.01), although 85% of patients with normal AMTS had MoCA < 26. CONCLUSIONS: The AMTS was feasible and valid in older acute medicine patients agreeing well with the MoCA albeit with a ceiling effect. Objective cognitive deficits were prevalent in patients without known dementia or delirium but were not reliably identified by subjective cognitive complaint or informant report.
Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos da Memória/diagnóstico , Admissão do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Demência/diagnóstico , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Testes Neuropsicológicos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
IL-17+ CD4+ T (Th17) cells contribute to the pathogenesis of several human inflammatory diseases. Here we demonstrate that TNF inhibitor (TNFi) drugs induce the anti-inflammatory cytokine IL-10 in CD4+ T cells including IL-17+ CD4+ T cells. TNFi-mediated induction of IL-10 in IL-17+ CD4+ T cells is Treg-/Foxp3-independent, requires IL-10 and is overcome by IL-1ß. TNFi-exposed IL-17+ CD4+ T cells are molecularly and functionally distinct, with a unique gene signature characterized by expression of IL10 and IKZF3 (encoding Aiolos). We show that Aiolos binds conserved regions in the IL10 locus in IL-17+ CD4+ T cells. Furthermore, IKZF3 and IL10 expression levels correlate in primary CD4+ T cells and Aiolos overexpression is sufficient to drive IL10 in these cells. Our data demonstrate that TNF-α blockade induces IL-10 in CD4+ T cells including Th17 cells and suggest a role for the transcription factor Aiolos in the regulation of IL-10 in CD4+ T cells.
Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Interleucina-10/metabolismo , Células Th17/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Sequência de Bases , Estudos de Casos e Controles , Bovinos , Células Cultivadas , Sequência Conservada , Cães , Humanos , Fator de Transcrição Ikaros/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Dados de Sequência Molecular , Ratos , Homologia de Sequência do Ácido Nucleico , Células Th17/metabolismoRESUMO
Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.
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Antioxidantes/metabolismo , Longevidade/fisiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Aconitato Hidratase/metabolismo , Animais , Biomarcadores , Composição Corporal/efeitos dos fármacos , Composição Corporal/genética , Composição Corporal/fisiologia , Catalase/sangue , Gorduras na Dieta/efeitos adversos , Ácidos Graxos/metabolismo , Resistência à Insulina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Musculares/biossíntese , Proteínas Musculares/genética , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Superóxido Dismutase/metabolismo , Triglicerídeos/sangueRESUMO
OBJECTIVE: To examine in mice the acute effects of epigallocatechin gallate (EGCG), a green tea bioactive polyphenol on substrate metabolism with focus on the fate of dietary lipids. METHODS: Male C57BL/6 mice were fed high-fat diets supplemented with EGCG extracted from green tea (TEAVIGO, DSM Nutritional Products Ltd, Basel, Switzerland) at different dosages up to 1% (w/w). Effects of EGCG on body composition (quantitative magnetic resonance), food intake and digestibility, oxidation and incorporation of exogenous lipids (stable isotope techniques: (13)C-labeled palmitate and diet supplemented with corn oil as a natural source of (13)C-enriched lipids) as well as gene expression (quantitative real-time PCR) in liver and intestinal mucosa were investigated. RESULTS: Short-term supplementation (4-7 days) of dietary EGCG increased energy excretion, while food and energy intake were not affected. Fecal energy loss was accompanied by increased fat and nitrogen excretion. EGCG decreased post-prandial triglyceride and glycogen content in liver, increased oxidation of dietary lipids and decreased incorporation of dietary 13C-enriched lipids into fat tissues, liver and skeletal muscle. EGCG dose dependently reversed high-fat diet-induced effects on intestinal substrate transporters (CD36, FATP4 and SGLT1) and downregulated lipogenesis-related genes (ACC, FAS and SCD1) in liver in the post-prandial state. CONCLUSIONS: Anti-obesity effects of EGCG can be explained by a decreased food digestibility affecting substrate metabolism of intestinal mucosa and liver, leading to increased post-prandial fat oxidation and reduced incorporation of dietary lipids into tissues.
Assuntos
Tecido Adiposo/metabolismo , Antioxidantes/farmacologia , Catequina/análogos & derivados , Suplementos Nutricionais , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Animais , Composição Corporal/efeitos dos fármacos , Catequina/farmacologia , Dieta Hiperlipídica , Ingestão de Alimentos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , CháRESUMO
An amine-based anion exchange resin dispersed in a flat sheet of polypropylene was prepared in alkaline forms so that it would capture carbon dioxide from air. The resin, with quaternary ammonium cations attached to the polymer structure and hydroxide or carbonate groups as mobile counterions, absorbs carbon dioxide when dry and releases it when wet. In ambient air, the moist resin dries spontaneously and subsequently absorbs carbon dioxide. This constitutes a moisture induced cycle, which stands in contrast to thermal pressure swing based cycles. This paper aims to determine the isothermal performance of the sorbent during such a moisture swing. Equilibrium experiments show that the absorption and desorption process can be described well by a Langmuir isothermal model. The equilibrium partial pressure of carbon dioxide over the resin at a given loading state can be increased by 2 orders of magnitude by wetting the resin.
Assuntos
Ar/análise , Dióxido de Carbono/química , Umidade , Absorção , Adsorção , Microscopia Eletrônica de Varredura , Modelos Químicos , TemperaturaRESUMO
A microsystem integrating electrochemical detection for the simultaneous detection of protein markers of breast cancer is reported. The microfluidic platform was realized by high precision milling of polycarbonate sheets and features two well distinguishable sections: a detection zone incorporating the electrode arrays and the fluid storage part. The detection area is divided into separate microfluidic chambers addressing selected electrodes for the measurement of samples and calibrators. The fluidic storage part of the platform consists of five reservoirs to store the reagents and sample, which are interfaced by septa. These reservoirs have the appropriate volume to run a single assay per cartridge and are manually filled. The liquids from the reservoirs are actuated by applying a positive air pressure (i.e.via a programmable syringe pump) through the septa and are driven to the detection zone via two turning valves. The application of the realised platform in the individual and simultaneous electrochemical detection of proteic cancer markers with very low detection limits are demonstrated. The microsystem has also been validated using real patient serum samples and excellent correlation with ELISA results obtained.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Técnicas Eletroquímicas/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Anticorpos Imobilizados/química , Neoplasias da Mama/diagnóstico , Desenho de Equipamento , Feminino , Humanos , Técnicas Analíticas Microfluídicas/métodos , Modelos BiológicosRESUMO
The potential of CD154 (CD40L) as a powerful immunological adjuvant has been shown in various strategies. In this study we examine the immunogenicity and protective efficacy of a CD40-targeting avian influenza hemagglutinin (HA) subunit DNA vaccine in ducks. DNA constructs encoded the ectodomain of the HA protein of LPAI A/mallard/BC/373/2005 (H5N2) with or without fusion to the ectodomain of duck CD154. CD40-targeting significantly accelerated and enhanced humoral responses to the vector-encoded HA protein. In viral challenge experiments with A/chicken/Vietnam/14/2005 (H5N1), DNA immunization conferred partial protection against the genetically distant HPAI. The observed improved kinetics and magnitude of immune induction suggest that CD40-targeting holds promise for influenza A vaccine development.
Assuntos
Ligante de CD40/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/prevenção & controle , Vacinas de DNA/imunologia , Estruturas Animais/patologia , Animais , Anticorpos Antivirais/sangue , Ligante de CD40/genética , Proteção Cruzada , Patos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Histocitoquímica , Vacinas contra Influenza/genética , Influenza Aviária/patologia , Microscopia , Testes de Neutralização , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinas de DNA/genética , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
PURPOSE: To determine the frequency and volume of seroma after breast-conserving surgery (BCS) with or without intraoperative radiotherapy (IORT). METHODS AND MATERIALS: Seventy-one patients with 73 breast cancers (IORT group) treated with IORT (20 Gy Intrabeam) as a boost during BCS were compared with 86 patients with 88 breast tumors (NO-IORT group) treated without IORT. Clinical examination and measurement of seroma volume on treatment-planning CT (CT-seroma) was done at median interval of 35 days after BCS. RESULTS: Seroma were found on palpation in 37 patients (23%) and on CT in 105 patients (65%; median volume, 26.3 mL). Interval between BCS and CT was significantly shorter in patients with palpable seroma (median, 33 days) or CT-seroma (33 days) compared with those with no palpable seroma (36.5 days; p = 0.027) or CT-seroma (52 days, p < 0.001). The rate of palpable seroma was not different (IORT n = 17, 23%; NO-IORT n = 20, 23%; p = 0.933), whereas fewer patients required puncture in the IORT group [3 (4%) vs. 10 (11%)]. In contrast, more patients showed CT-seroma after IORT (IORT n = 59, 81%; NO-IORT n = 46, 52%; p < 0.001). The interval between BCS and CT was significantly shorter in patients with IORT as compared with the NO-IORT patients (median, 33 days vs. 41.5 days; p = 0.036). CONCLUSION: Intraoperative radiotherapy with low-kilovoltage X-rays during BCS is not associated with an increased rate of palpable seroma or seroma requiring treatment. The rate of seroma formation on CT was higher after IORT compared with the NO-IORT group, which might be because of the shorter interval between BCS and CT.
Assuntos
Doenças Mamárias/etiologia , Neoplasias da Mama/radioterapia , Seroma/etiologia , Antineoplásicos/administração & dosagem , Mama/patologia , Doenças Mamárias/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Período Intraoperatório , Mastectomia Segmentar , Pessoa de Meia-Idade , Tamanho do Órgão , Palpação , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Seroma/diagnóstico , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
AIMS/HYPOTHESIS: High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. METHODS: Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr ( -/- )) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20-26 weeks of intervention, n = 8-10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. RESULTS: Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr ( -/- ) vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. CONCLUSIONS/INTERPRETATION: The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial.
Assuntos
Dieta , Polipeptídeo Inibidor Gástrico/fisiologia , Índice Glicêmico , Fatores Etários , Animais , Glicemia/análise , Composição Corporal , Calorimetria , Ingestão de Energia/fisiologia , Teste de Tolerância a Glucose , Insulina/sangue , Masculino , Camundongos , Camundongos Knockout , Receptores dos Hormônios Gastrointestinais/genética , Receptores dos Hormônios Gastrointestinais/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Triglicerídeos/metabolismoRESUMO
The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO<1.96 W) had higher NTproANP and NTproBNP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.
Assuntos
Fator Natriurético Atrial/sangue , Exercício Físico/fisiologia , Insuficiência Cardíaca/sangue , Isquemia Miocárdica/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Precursores de Proteínas/sangue , Relaxina/sangue , Adulto , Idoso , Biomarcadores/sangue , Cateterismo Cardíaco , Teste de Esforço , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , PrognósticoRESUMO
In electrokinetic trapping (EKT), the electroosmotic velocity of a buffer solution in one area of a microfluidic device opposes the electrophoretic velocity of the analyte in a second area, resulting in transport of DNA to a location where the electrophoretic and electroosmotic velocities are equal and opposite and DNA concentrates at charged nanochannels. The method does not require an optical plug localization, a considerable advantage as compared to preconcentration techniques previously presented. In the work reported here, the trapping process is preceded by a field-amplification in the sample reservoir to reduce trapping time, as field-amplified EKT is shown to be an effective technique to preconcentrate samples from larger volumes. A theoretical model explaining the principle of field-amplified EKT considers different ionic strengths and cross-sectional areas in the microchip segments. The model is supported by experimental data using nucleic acids and fluorescein as sample analytes. An incorporated poly(ethylene terephthalate) (PET) membrane provides anion exclusion due to a negatively charged surface. A fluidic counter flow supports the trapping process in 100 nm pores due to anion exclusion. An analysis of Joule heating gives evidence that temperature gradient focusing effects are negligible and charge exclusion is responsible for trapping. The theoretical model developed and experimentally demonstrated can be exploited for the preconcentration of cell free fetal DNA circulating in maternal plasma and other rare nucleic acid species present in large sample volumes.
Assuntos
Métodos Analíticos de Preparação de Amostras/instrumentação , DNA/isolamento & purificação , Membranas Artificiais , Polietilenotereftalatos/química , Sistema Livre de Células , DNA/análise , DNA/sangue , DNA/química , Condutividade Elétrica , Eletroforese , Fluoresceína/química , Fluoresceína/isolamento & purificação , Técnicas Analíticas Microfluídicas , Modelos Químicos , Neoplasias/diagnóstico , Porosidade , TemperaturaRESUMO
BACKGROUND: In the treatment of ruptured abdominal aortic aneurysm (rAAA), the results of open graft replacement (OGR) have remained constant but discouraging for the last 4 decades. Provided suitable anatomy, elective endovascular abdominal aortic aneurysm repair (EVAR) is less invasive and leads to improved perioperative mortality. Thus, it is reasonable to assume that endovascular treatment should improve the results of rAAA therapy. OBJECTIVE: To determine whether the use of both endovascular and open repair of rAAA leads to improved results. DESIGN: A single-center, retrospective analysis of 89 patients suffering from rAAA treated either by EVAR or OGR. PATIENTS: From October 1999 until July 2006, a consecutive series of patients with rAAA were analyzed. Time was divided into 2 periods of 41 months. During the first period, 42 patients were treated by OGR exclusively. Period 2 started with the availability of an EVAR protocol to treat rAAA; 31 patients received open repair while 16 patients underwent EVAR. MAIN OUTCOME MEASURES: Kaplan-Meier survival estimates were calculated and compared. RESULTS: Survival estimates showed a statistically significant reduction in overall postoperative mortality following the introduction of EVAR (P < .03). The 90-day overall mortality rate was reduced from 54.8% to 27.7% during the second period (P < .01). Survival of patients older than 75.5 years was especially improved (75% vs 28.6%; P < .01). There was a parallel pattern of significant reduction of the mortality rate after OGR to 29% (P < .03). CONCLUSION: Offering both EVAR and OGR to patients with rAAA leads to significant improvements in postoperative survival.