RESUMO
A Fluidyne engine is a liquid piston Stirling engine that uses thermally induced self-sustained oscillations of water and air that are filled in a looped tube and tuning column. It presents high potential for use as a low-temperature-difference Stirling engine with a simple structure. This study analyzes the linear oscillation dynamics of the Fluidyne from a thermoacoustic point of view, with particular emphasis on the local specific acoustic impedance of the working gas, which is given by the ratio of the complex amplitudes of the pressure and velocity oscillations in the regenerator of the Fluidyne. The frequency dependence of the specific acoustic impedance indicates that the gas in the regenerator region undergoes a thermodynamic cycle equivalent to the Stirling cycle when the oscillation frequency is equal to the natural oscillation frequency of the U-shaped liquid column in the Fluidyne. The analysis of the natural oscillation modes determined two key parameters for the desired specific acoustic impedance: the tuning column length and the connecting position to the loop. Experimental verification was achieved via measurements of the onset temperature ratio and acoustic field of a prototype Fluidyne engine.
RESUMO
BACKGROUND AND AIMS: Low serum albumin level is reportedly associated with worse clinical outcomes in patients with chronic kidney disease (CKD). However, associations between decreased serum albumin level and outcomes in non-CKD patients with coronary artery disease (CAD) remain unclear. Therefore, we aimed to evaluate the prognostic value of serum albumin concentrations in stable CAD patients with preserved renal function. METHODS AND RESULTS: We studied 1316 patients with CAD and preserved renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) who underwent their first PCI between 2000 and 2011 and had data available for pre-procedural serum albumin. Patients were assigned to quartiles based on pre-procedural albumin concentrations. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, was evaluated. Mean albumin concentration was 4.1 ± 0.4 g/dL. During the median follow-up of 7.5 years, 181 events occurred (13.8%). Kaplan-Meier curves revealed that patients with decreased serum albumin concentrations showed a higher event rate for MACE (log-rank, p < 0.0001). Using the highest tertiles (>4.3 g/dL) as reference, adjusted hazard ratios were 1.97 (95% CI, 1.12-3.55), 1.77 (95% CI, 0.99-3.25), and 1.19 (95% CI, 0.68-2.15) for serum albumin concentrations of <3.9, 3.9-4.0, and 4.1-4.3 g/dL, respectively. Decreased serum albumin concentration was associated with MACE even after adjusting for other independent variables (HR, 2.21 per 1-g/dL decrease; 95% CI, 1.37-3.56, p = 0.001). CONCLUSION: Decreased serum albumin concentration independently predicted worse long-term prognosis in non-CKD patients after PCI. Pre-procedural serum albumin concentration could offer a useful predictor for patients with CAD and preserved renal function.
Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Hipoalbuminemia/sangue , Rim/fisiopatologia , Intervenção Coronária Percutânea , Albumina Sérica Humana/metabolismo , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/mortalidade , Hipoalbuminemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoAssuntos
Exantema/induzido quimicamente , Nivolumabe/efeitos adversos , Vemurafenib/uso terapêutico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Exantema/diagnóstico , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Índice de Gravidade de Doença , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Exantema/induzido quimicamente , Indóis/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Sulfonamidas/efeitos adversos , Adulto , Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Humanos , Indóis/administração & dosagem , Neoplasias Pulmonares/secundário , Melanoma/patologia , Nivolumabe , Neoplasias Cutâneas/patologia , Sulfonamidas/administração & dosagem , VemurafenibRESUMO
For determination of the physiological role and mechanism of vacuolar proteolysis in the yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, and carboxypeptidase Y were transferred from a nutrient medium to a synthetic medium devoid of various nutrients and morphological changes of their vacuoles were investigated. After incubation for 1 h in nutrient-deficient media, a few spherical bodies appeared in the vacuoles and moved actively by Brownian movement. These bodies gradually increased in number and after 3 h they filled the vacuoles almost completely. During their accumulation, the volume of the vacuolar compartment also increased. Electron microscopic examination showed that these bodies were surrounded by a unit membrane which appeared thinner than any other intracellular membrane. The contents of the bodies were morphologically indistinguishable from the cytosol; these bodies contained cytoplasmic ribosomes, RER, mitochondria, lipid granules and glycogen granules, and the density of the cytoplasmic ribosomes in the bodies was almost the same as that of ribosomes in the cytosol. The diameter of the bodies ranged from 400 to 900 nm. Vacuoles that had accumulated these bodies were prepared by a modification of the method of Ohsumi and Anraku (Ohsumi, Y., and Y. Anraku. 1981. J. Biol. Chem. 256:2079-2082). The isolated vacuoles contained ribosomes and showed latent activity of the cytosolic enzyme glucose-6-phosphate dehydrogenase. These results suggest that these bodies sequestered the cytosol in the vacuoles. We named these spherical bodies "autophagic bodies." Accumulation of autophagic bodies in the vacuoles was induced not only by nitrogen starvation, but also by depletion of nutrients such as carbon and single amino acids that caused cessation of the cell cycle. Genetic analysis revealed that the accumulation of autophagic bodies in the vacuoles was the result of lack of the PRB1 product proteinase B, and disruption of the PRB1 gene confirmed this result. In the presence of PMSF, wild-type cells accumulated autophagic bodies in the vacuoles under nutrient-deficient conditions in the same manner as did multiple protease-deficient mutants or cells with a disrupted PRB1 gene. As the autophagic bodies disappeared rapidly after removal of PMSF from cultures of normal cells, they must be an intermediate in the normal autophagic process. This is the first report that nutrient-deficient conditions induce extensive autophagic degradation of cytosolic components in the vacuoles of yeast cells.
Assuntos
Autofagia/fisiologia , Macrolídeos , Saccharomyces cerevisiae/fisiologia , Vacúolos/fisiologia , Acetatos/farmacologia , Antibacterianos/farmacologia , Autofagia/efeitos dos fármacos , Calcimicina/farmacologia , Carbono/metabolismo , Cloranfenicol/farmacologia , Cicloeximida/farmacologia , Endopeptidases/genética , Endopeptidases/metabolismo , Etilmaleimida/farmacologia , Nitrogênio/metabolismo , Proteínas/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/ultraestrutura , Vacúolos/efeitos dos fármacos , Vacúolos/ultraestruturaRESUMO
BACKGROUND: Low-dose methotrexate (MTX) therapy is widely used in the treatment of rheumatoid arthritis (RA). Though the difference in response to MTX between patients with RA is large, the factors that contribute to this variability remain unclear. OBJECTIVE: We aimed to identify those factors with a particular emphasis on the pharmacogenetics of MTX. METHOD: We evaluated the association of possible factors, including genetic polymorphisms of folate metabolic pathway enzymes, with the cumulative value of C-reactive protein, an index of MTX anti-inflammatory efficacy, in 87 Japanese patients with RA. RESULTS: Polymorphisms of the reduced folate carrier gene (RFC) G80A and of the gamma-glutamylhydrolase gene (GGH) C-401T were more closely associated (beta = 2.1194, P = 0.0017) than other polymorphisms, with the anti-inflammatory response to MTX. CONCLUSION: Patients with RA having RFC 80A and GGH-401T alleles were less responsive to MTX than those with RFC 80A and without GGH-401T alleles. Thus, this data may be useful for guiding treatment of RA patients with MTX.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Farmacogenética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artrite Reumatoide/genética , Biomarcadores Farmacológicos/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Humanos , Japão , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Proteína Carregadora de Folato Reduzido , gama-Glutamil Hidrolase/genéticaRESUMO
Aflatoxin B1 (AFB1) was detected in serum samples of healthy Japanese males by radioimmunoassay and high-performance liquid chromatography. Blood samples were obtained from 20 subjects after fasting and from 80 subjects after lunch. The subjects ranged in age from 20 to 63 years of age. Measurement of AFB1 in the samples was performed by radioimmunoassay and was confirmed by high-performance liquid chromatography using a mu Porasil column and a C18-mu Bondapak column after the conversion of AFB1 to its water adduct AFB2a. AFB1 was detected in 5 of 20 fasting blood samples [20 to 56 pg/ml of serum; 33.6 +/- 14.6 (S.D.)] and in 29 of 80 serum samples taken after lunch (20 to 1169 pg/ml of serum; 218.1 +/- 268.3). Mass spectral analysis of the material obtained after high-performance liquid chromatography separation from serum samples confirmed the presence of AFB1.
Assuntos
Aflatoxinas/análise , Carcinógenos/análise , Adulto , Aflatoxina B1 , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Japão , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Radioimunoensaio/métodosRESUMO
Mucin-type O-glycans on leukocytes acquire functions once they contain core 2 branches, which can be synthesized by core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT). Recently, understanding the roles of mucin-type O-glycans has been significantly advanced by generating transgenic mice overexpressing C2GnT or knockout mice defective in C2GnT. This review article summarizes previous results implicating the roles of mucin-type O-glycans and the most recent studies to test such a hypothesis. These results, taken together, demonstrate that mucin-type O-glycans either facilitate or attenuate cell adhesion depending on the structures of non-reducing termini.
Assuntos
Antígenos CD/química , Adesão Celular , Mucinas/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Sialoglicoproteínas/química , Animais , Antígenos CD/genética , Biomarcadores Tumorais/análise , Sequência de Carboidratos , Linhagem Celular , DNA Complementar/química , Humanos , Leucossialina , Antígenos do Grupo Sanguíneo de Lewis , Antígenos CD15 , Dados de Sequência Molecular , Peso Molecular , N-Acetilglucosaminiltransferases/genética , Oligossacarídeos/análise , Sialoglicoproteínas/genética , Linfócitos T/química , Linfócitos T/enzimologia , Linfócitos T/imunologia , Timo/química , Timo/citologia , Células Tumorais Cultivadas , Síndrome de Wiskott-Aldrich/imunologiaRESUMO
Cells of Saccharomyces cerevisiae were grown aerobically and anaerobically, and levels of the protective compounds, cysteine and glutathione, and activities of defensive enzymes, catalase and superoxide dismutase, against an oxygen stress were determined and compared in both cells. Aerobiosis increased both the compounds and enzyme activities. The elevated synthesis of glutathione could be associated with the increased levels of cysteine which in its turn was found to be controlled by the oxygen-dependent activation of cystathionine beta-synthase.
Assuntos
Estresse Oxidativo , Saccharomyces cerevisiae/fisiologia , Aerobiose , Ar , Anaerobiose , Northern Blotting , Western Blotting , Catalase/metabolismo , Cistationina beta-Sintase/metabolismo , Cisteína/metabolismo , Ativação Enzimática , Glutationa/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Superóxido Dismutase/metabolismoRESUMO
A trihexacontapeptide corresponding to the sequence 8-70 of eglin c and its related peptides were synthesized by the conventional solution method and their inhibitory activity against human leukocyte elastase, cathepsin G and alpha-chymotrypsin was examined. Although synthetic eglin c (41-49) inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.0 x 10(-5) M and 2.0 x 10(-5) M, respectively) but not leukocyte elastase, the synthetic trihexacontapeptide potently inhibited cathepsin G, alpha-chymotrypsin and leukocyte elastase (Ki = 1.8 x 10(-9) M, 1.4 x 10(-9) M and 2.2 x 10(-9) M, respectively). The relationship between the structure of eglin c and the inhibitory activity against the above enzymes is also described.
Assuntos
Catepsinas/antagonistas & inibidores , Quimotripsina/antagonistas & inibidores , Elastase Pancreática/antagonistas & inibidores , Fragmentos de Peptídeos/síntese química , Inibidores de Serina Proteinase/química , Serpinas , Sequência de Aminoácidos , Catepsina G , Eletroquímica , Humanos , Ligação de Hidrogênio , Elastase de Leucócito , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Proteínas , Serina Endopeptidases , Relação Estrutura-AtividadeRESUMO
The isolated dog retinal pigment epithelium (RPE)-choroid was gently stretched on the inner surface of a spherical stainless mesh, retinal side upward, and clamped between half-chambers made of Kel-F. The volume flow across the tissue was monitored by the movement of water in capillary tubes connected to both chambers. With zero pressure difference across the RPE-choroid, retina-to-choroid fluid flow was determined to be 6.4 microliters/hr/cm2 (absorption). Removal of HCO-3 from the solution did not affect the fluid flow. However, the flow was reduced 88% in Cl- -free medium, indicating a coupling between water and Cl- absorption. The flow was also inhibited by ouabain (10(-5) M) and furosemide (10(-4) M). Hydraulic conductivity (Lp) of the RPE-choroid was determined to be 0.0126 microliters/min/cm2/mm Hg which places the dog RPE-choroid in the category of a "leaky" epithelium.
Assuntos
Epitélio Pigmentado Ocular/metabolismo , Animais , Bicarbonatos/farmacologia , Cloretos/farmacologia , Cães , Feminino , Furosemida/farmacologia , Técnicas In Vitro , Masculino , Concentração Osmolar , Ouabaína/farmacologia , Fisiologia/instrumentaçãoRESUMO
The retinal pigment epithelium (RPE)-choroid was isolated from cynomolgus monkey eyes with experimental retinal detachments and the volume flow was determined in vitro using Ussing-type chambers. With zero pressure difference across the membrane, retina-to-choroid volume flow was 5.0 microliter/hr/cm2 in eyes with subacute retinal detachments (1-2 weeks). In eyes with chronic retinal detachment (8-20 months), the flow was 7.3 microliter/hr/cm2. Volume flow was not affected by the elimination of ambient bicarbonate. Transepithelial potential difference and resistance were 8.9 mV, retinal side positive, and 339 ohm-cm2, respectively, in chronic retinal detachments. It is concluded that there is a posteriorly directed flow of fluid across the RPE in cynomolgus monkey eyes with chronic retinal detachments.
Assuntos
Líquidos Corporais , Epitélio Pigmentado Ocular/fisiopatologia , Descolamento Retiniano/fisiopatologia , Animais , Transporte Biológico , Feminino , Macaca fascicularis , MasculinoRESUMO
The inward permeability of the blood-retinal barrier to carboxyfluorescein was determined in monkey eyes with and without rhegmatogenous retinal detachment (RD). In the absence of changes in the diffusional permeability of the retinal pigment epithelium (RPE), inward permeability changes reflect changes in fluid flow across the RPE. Intravenous injection of mannitol resulted in a 15 mosmol/kg increase in plasma osmolality which decreased inward permeability 37% in eyes with RD and 21% in eyes with vitrectomy alone. When the intraocular pressure was raised 20 mm Hg above normal, inward permeability decreased 29% in eyes with RD and 32% in normal eyes. It is concluded that fluid flow across the blood-retinal barrier is influenced by both plasma osmolality and intraocular pressure.
Assuntos
Barreira Hematorretiniana , Sangue/fisiopatologia , Líquidos Corporais/fisiologia , Pressão Intraocular , Epitélio Pigmentado Ocular/fisiopatologia , Descolamento Retiniano/fisiopatologia , Animais , Transporte Biológico , Permeabilidade da Membrana Celular , Feminino , Fluoresceínas/fisiologia , Macaca fascicularis , Masculino , Concentração OsmolarRESUMO
The inward permeability of the blood-retinal barrier to carboxyfluorescein was determined in 12 cynomolgus monkeys. Probenecid (175 mg/kg), an inhibitor of active outward transport of carboxyfluorescein, did not affect the inward permeability, indicating that the inward permeability is independent of the active outward transport system. However, acetazolamide (20 mg/kg), which causes increased outward fluid movement across the retinal pigment epithelium (RPE), significantly reduced the inward permeability. Thus, inward diffusion of carboxyfluorescein interacts with outward fluid flow across the RPE. Since carboxyfluorescein has low lipid solubility and remains extracellular, it is concluded that the pathway of fluid movement and carboxyfluorescein diffusion across the RPE is paracellular.
Assuntos
Acetazolamida/farmacologia , Barreira Hematorretiniana/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Fluoresceínas/metabolismo , Animais , Feminino , Fluoresceínas/antagonistas & inibidores , Macaca fascicularis , Masculino , Probenecid/farmacologiaRESUMO
Outward and inward permeability of carboxyfluorescein across the blood-retinal barrier were measured fluorophotometrically in seven cynomolgus monkey eyes with experimental rhegmatogenous retinal detachment. Probenecid was used to inhibit outward transport of carboxyfluorescein. The outward permeability was 1.98 +/- 0.31 microliter/min in eyes with retinal detachment and 0.84 +/- 0.15 microliter/min in control eyes with vitrectomy alone (P less than 0.01). The inward permeability, determined separately following intravenous injection, was significantly lower than the outward permeability: 0.14 +/- 0.02 microliter/min for eyes with retinal detachment and 0.04 +/- 0.01 microliter/min for control eyes. Since the outward permeability minus the inward permeability in the presence of probenecid represents that fraction of tracer moving due to fluid flow, it may be concluded that outward flow of fluid across the blood-retinal barrier is a substantial contributor to carboxyfluorescein loss from the vitreous cavity following intravitreal injection.
Assuntos
Barreira Hematorretiniana/efeitos dos fármacos , Permeabilidade Capilar , Fluoresceínas/sangue , Descolamento Retiniano/metabolismo , Perfurações Retinianas/complicações , Animais , Transporte Biológico/efeitos dos fármacos , Olho/metabolismo , Injeções Intravenosas , Macaca fascicularis , Concentração Osmolar , Probenecid/farmacologia , Descolamento Retiniano/etiologiaRESUMO
Outward (retina to choroid) and inward (choroid to retina) permeabilities of carboxyfluorescein and fluorescein in the isolated dog retinal pigment epithelium (RPE)-choroid were determined. Outward permeability was 9 and 47 times larger than inward permeability for carboxyfluorescein and fluorescein, respectively. The outward permeability of carboxyfluorescein was seven times lower than that of fluorescein, whereas there was no statistical difference between the inward permeabilities. Carboxyfluorescein is thus distinguished from fluorescein by its low affinity to the outwardly directed organic anion transport system. 10(-4) M probenecid caused greater than 98% inhibition of the outward transport of 6 X 10(-5) M carboxyfluorescein and 6 X 10(-6) M fluorescein.
Assuntos
Fluoresceínas/metabolismo , Epitélio Pigmentado Ocular/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Corioide/metabolismo , Cães , Fluoresceína , Fluoresceínas/antagonistas & inibidores , Técnicas In Vitro , Concentração Osmolar , Permeabilidade , Probenecid/farmacologiaRESUMO
The integrity of the RPE barrier function in retinal detachment was studied in vitro. The retinal pigment epithelium (RPE)-choroid tissue was isolated from cynomolgus monkey eyes with acute (less than 1 hr), subacute (1-2 weeks), and chronic (8-20 months) retinal detachments, and clamped between Ussing-type chambers. Electrical characteristics and choroid-to-retina permeability to carboxyfluorescein were determined. In the HEPES-buffered bathing solution, transepithelial potential difference and resistance in eyes with acute retinal detachments (0.2 mV and 134 ohm-cm2, respectively) were significantly lower than subacute (7.9 and 350) and chronic (10.4 and 348) retinal detachments. Furthermore, the permeability was increased five-fold in acute retinal detachments with respect to subacute and chronic retinal detachments, indicating a breakdown of the RPE barrier in acute retinal detachment. No statistical difference was found between subacute and chronic retinal detachments. In this animal model, RPE barrier function is destroyed at the onset of retinal detachment, but recovers in a week or two, and is maintained in the chronic stage. Histological examination revealed that RPE recovery was accomplished by RPE proliferation and hyperplasia.