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We report on the first subpicometer interferometer flown in space. It was part of ESA's Laser Interferometer Space Antenna (LISA) Pathfinder mission and performed the fundamental measurement of the positional and angular motion of two free-falling test masses. The interferometer worked immediately, stably, and reliably from switch on until the end of the mission with exceptionally low residual noise of 32.0_{-1.7}^{+2.4} fm/sqrt[Hz], significantly better than required. We present an upper limit for the sensor performance at millihertz frequencies and a model for the measured sensitivity above 200 mHz.
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This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, 12 men performed two low-volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing pronounced mechanical/metabolic stress, and a high-volume moderate-intensity continuous exercise protocol (MIC) inducing mild but prolonged mechanical/metabolic stress. Gene and protein expression of angiogenic factors was determined in vastus lateralis muscle samples obtained before and after exercise. Exercise upregulated muscle VEGF mRNA to a greater extent in LSI and MIC compared with SSI. Analysis of angiogenic factors sensitive to shear stress revealed more marked exercise-induced VEGF receptor 2 (VEGF-R2) mRNA responses in MIC than SSI, as well as greater platelet endothelial cell adhesion molecule (PECAM-1) and endothelial nitric oxide synthase (eNOS) mRNA responses in LSI than SSI. No apparent exercise-induced phosphorylation of shear stress-sensory proteins VEGF-R2Tyr1175, PECAM-1Tyr713, and eNOSSer1177 was observed despite robust elevations in femoral artery shear stress. Exercise evoked greater mRNA responses of the mechanical stretch sensor matrix metalloproteinase-9 (MMP9) in SSI than MIC. Exercise-induced mRNA responses of the metabolic stress sensor hypoxia-inducible factor-1α (HIF-1α) were more profound in LSI than SSI. These results suggest that low-volume high-intensity exercise transcriptionally activates angiogenic factors in a mechanical/metabolic stress-dependent manner. Furthermore, the angiogenic potency of low-volume high-intensity exercise appears similar to that of high-volume moderate-intensity exercise, but only on condition of eliciting severe mechanical/metabolic stress. We conclude that the angiogenic stimulus produced by exercise depends on both magnitude and protraction of myocellular homeostatic perturbations.NEW & NOTEWORTHY Skeletal muscle capillary growth is orchestrated by angiogenic factors sensitive to mechanical and metabolic signals. In this study, we employed an integrative exercise model to synergistically target, yet to different extents and for different durations, the mechanical and metabolic components of muscle activity that promote angiogenesis. Our results suggest that the magnitude of the myocellular perturbations incurred during exercise determines the amplitude of the angiogenic molecular signals, implying hormetic modulation of skeletal muscle angiogenesis by exercise-induced mechanical and metabolic stress.
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Proteínas Angiogénicas/metabolismo , Metabolismo Energético , Hormesis , Contracción Muscular , Músculo Cuádriceps/irrigación sanguínea , Músculo Cuádriceps/metabolismo , Estrés Fisiológico , Adulto , Proteínas Angiogénicas/genética , Ciclismo , Estudios Cruzados , Hemodinámica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Consumo de Oxígeno , Resistencia Física , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Distribución Aleatoria , Factores de Tiempo , Activación Transcripcional , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.
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We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.
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Degenerative diseases of the central nervous system, the incidence and prevalence of which vary between men and women, often manifest in the hippocampus. Neurosteroids are hormones that are synthesized in the CNS, and it is here that they exert their influence. Estrogen and testosterone are examples of neurosteroid hormones. In the hippocampus, an area of the brain closely associated with learning and memory, the local synthesis of estrogen in females, but not in males, is essential for the plasticity and stability of the synapses. The inhibition of estrogen synthesis in the female hippocampus causes a reduction in long-term potentiation (LTP), an electrophysiological parameter of learning and memory, thus resulting in a significant loss of synapses. In light of this, the fact that estrogen has been attributed with many neuroprotective functions in degenerative diseases of the CNS suggests that therapeutic concepts involving the use of estrogen are possibly only effective in women, but not in men. These findings similarly provide a basis for explaining the gender dimorphism that has been found in certain degenerative illnesses of the CNS.
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Hormonas Esteroides Gonadales/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Modelos Neurológicos , Enfermedades Neurodegenerativas/metabolismo , Neurotransmisores/metabolismo , Transmisión Sináptica/fisiología , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
Methods to control polymorphic modifications of phthalocyanines using optical (laser) radiation and possible photoinduced transformations of polymorphs are of practical interest in problems of identification and attribution of paintings, laser (micro)sampling, and the development of phthalocyanine structures for technical applications in optics, optoelectronics, and medicine. In this work, we compare the thermal and laser-induced changes of a gouache paint layer based on copper phthalocyanine (CuPc) PB15. The thermally induced color changes of the paint layer are quantified using the CIE Lab D65/10 color space. (Nano)rods formed in the paint layer when the sample is heated to 450°C at normal pressure without humidity control are studied using absorption spectroscopy, Raman microspectroscopy, and scanning electron microscopy. It is shown that the formation of (nano)rods is related to the αâß polymorph transition of CuPc. Low-frequency markers of the CuPc ß-polymorph are revealed in the Raman spectra. For the sample containing (nano)rods, the a* color coordinate substantially increases (by about 30 units), whereas the L* and b* coordinates remain almost unchanged. Irradiation with a single nanosecond laser pulse at a wavelength of 532 nm leads to the laser ablation of the paint layer at fluences exceeding a threshold level of about 3 J/cm2. Irradiation at fluences of greater than 0.5 J/cm2, but lower than the ablation threshold leads to color change of the paint layer due to the αâε transition of CuPc. Similar transformations are observed at the periphery of and inside ablation crater.
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It was a widely held belief that sex steroids, namely testosterone and 17ß-estradiol (E2) of gonadal origin, control synaptic plasticity in the hippocampus. A new paradigm emerged when it was shown that these sex steroids are synthesized in the hippocampus. The inhibition of sex steroids in the hippocampus impairs synaptic plasticity sex-dependently in this region of the brain. In gonadectomized animals and in hippocampal cultures, inhibition of estradiol synthesis in female animals and in cultures from female animals, and inhibition of dihydrotestosterone synthesis in male animals and in cultures of male animals, cause synapse loss and impair LTP in the hippocampus, but not vice versa. Since the hippocampal cultures originated from perinatal animals, and due to the similarity of in vivo and in vitro findings, it appears that hippocampal neurons are differentiated in a sex-specific manner during the perinatal period when sexual imprinting takes place.
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Estradiol/metabolismo , Hipocampo/citología , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Testosterona/metabolismo , Animales , Células Cultivadas , Femenino , Humanos , MasculinoRESUMEN
Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium able to survive in diverse environments such as soil, plants, freshwater, and seawater. P. aeruginosa can be an opportunistic pathogen to humans when their immune system is deficient. Its pathogenicity may be linked to the production of virulence factors. We isolated P. aeruginosa strain RBS from the saltern of Sfax in Tunisia. In this study, we characterized the halotolerance, antibiotic susceptibility, and some virulence factors of strain RBS. High NaCl concentrations inhibited growth and motility. However, biofilm formation was enhanced to protect bacteria against salt stress. Among the 18 antibiotics tested, quinolones and tetracycline showed a significant inhibitory effect on growth, motility, and biofilm formation of strain RBS. ß-Lactams, however, did not have any inhibitory effect on neither bacterial growth nor motility. In some cases, resistance was due, in part, to biofilm formation. We also showed that RBS produces two proteases, LasB and AprA, which have been shown to be implicated in host infection. LasB was further characterized to study the role of metal ions in enzyme stability. It possesses two distinct metal ion-binding sites coordinating a calcium and a zinc ion. The effect of metal ion chelation was evaluated as well as substitutions of residues involved in metal ion binding. Impairing metal ion binding of LasB led to a loss of activity and a sharp decrease of stability. Our findings suggest that the binding of both metal ions is interdependent as the two metal ions' binding sites are linked via a hydrogen bond network.
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Iones/metabolismo , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidad , Factores de Virulencia/metabolismo , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Humanos , Péptido Hidrolasas/metabolismo , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , TúnezRESUMEN
AIMS/HYPOTHESIS: TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that does not involve modulation at proximal insulin signalling intermediates. We hypothesised that signalling through TBC1D4 is involved in this effect of exercise as it is a common signalling element for insulin and exercise. METHODS: Insulin-regulated glucose metabolism was evaluated in 12 healthy moderately trained young men 4 h after one-legged exercise at basal and during a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis biopsies were taken before and immediately after the clamp. RESULTS: Insulin stimulation increased glucose uptake in both legs, with greater effects (approximately 80%, p < 0.01) in the previously exercised leg. TBC1D4 phosphorylation, assessed using the phospho-AKT (protein kinase B)substrate antibody and phospho- and site-specific antibodies targeting six phosphorylation sites on TBC1D4, increased at similar degrees to insulin stimulation in the previously exercised and rested legs (p < 0.01). However, TBC1D4 phosphorylation on Ser-318, Ser-341, Ser-588 and Ser-751 was higher in the previously exercised leg, both in the absence and in the presence of insulin (p < 0.01; Ser-588, p = 0.09; observed power = 0.39). 14-3-3 binding capacity for TBC1D4 increased equally (p < 0.01) in both legs during insulin stimulation. CONCLUSION/INTERPRETATION: We provide evidence for site-specific phosphorylation of TBC1D4 in human skeletal muscle in response to physiological hyperinsulinaemia. The data support the idea that TBC1D4 is a nexus for insulin- and exercise-responsive signals that may mediate increased insulin action after exercise.
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Ejercicio Físico/fisiología , Proteínas Activadoras de GTPasa/fisiología , Insulina/fisiología , Músculo Esquelético/fisiología , Tejido Adiposo/citología , Tejido Adiposo/fisiología , Adulto , Biopsia , Glucemia/metabolismo , Cartilla de ADN , Dieta , Proteínas Activadoras de GTPasa/genética , Proteínas Activadoras de GTPasa/metabolismo , Humanos , Hiperinsulinismo/etiología , Articulación de la Rodilla/fisiología , Pierna/fisiología , Masculino , Consumo de Oxígeno , Fosforilación , Descanso , Transducción de Señal , Posición Supina , Carga de Trabajo , Adulto JovenRESUMEN
Tannic acid mordanting during fixation of isolated vesicles from skeletal muscle enhanced the resolution of the images. Isolated triadic junctions displayed two characteristic features not previously described: (a) a clear gap separated terminal cisternae from transverse tubules; (b) this gap was bridged by a separating array of structures which resembled the "feet" of intact muscle. When the triad was broken in a French press and subsequently reassembled by joining the two organelles, a similar gap was seen but the structure of the feet was less well defined. When the membrane of the triad was extracted by Triton X-100, the junctional region was retained and a similar gap between the two organelles could be discerned. The terminal cisternae characteristically displayed a thickening of the cytoplasmic leaflet of the membrane in select areas in which electron-dense material was apposed on the luminal leaflet. This thickened membrane was not observed in longitudinal reticulum or in terminal cisternae regions distal to the electron-dense matter. This thickened leaflet was not invariably associated with the junction, and some junctional regions did not display discernible thickening of the membrane. When the triad was treated with KCl, the electron-dense aggregate was dispersed and the thickened leaflet of the terminal cisternae dissipated, whereas the triadic junctional region with its feet remained unchanged. KCl treatment caused dissolution of three proteins of Mr = 77,000, 43,000, and 38,000. Treatment of Triton-resistant vesicles with KCl caused the loss of electron-dense aggregate but did not otherwise influence the appearance of the junction. A good degree of correlation both qualitatively and in quantitative parameters between the isolated vesicles and the intact muscle was observed.
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Microscopía Electrónica/métodos , Músculos/ultraestructura , Organoides/ultraestructura , Animales , Citoplasma/ultraestructura , Taninos Hidrolizables/farmacología , Proteínas de la Membrana/metabolismo , Octoxinol , Polietilenglicoles/farmacología , Cloruro de Potasio , Conejos , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/ultraestructura , Coloración y EtiquetadoRESUMEN
The subcellular distribution of sarcolemmal dihydropyridine receptor (DHPR) and sarcoplasmic reticular triadin and Ca2+ release channel/ryanodine receptor (RyR) was determined in adult rabbit ventricle and atrium by double labeling immunofluorescence and laser scanning confocal microscopy. In ventricular muscle cells the immunostaining was observed primarily as transversely oriented punctate bands spaced at approximately 2-micron intervals along the whole length of the muscle fibers. Image analysis demonstrated a virtually complete overlap of the staining patterns of the three proteins, suggesting their close association at or near dyadic couplings that are formed where the sarcoplasmic reticulum (SR) is apposed to the surface membrane or its infoldings, the transverse (T-) tubules. In rabbit atrial cells, which lack an extensive T-tubular system, DHPR-specific staining was observed to form discrete spots along the sarcolemma but was absent from the interior of the fibers. In atrium, punctate triadin- and RyR-specific staining was also observed as spots at the cell periphery and image analysis indicated that the three proteins were co-localized at, or just below, the sarcolemma. In addition, in the atrial cells triadin- and RyR-specific staining was observed to form transverse bands in the interior cytoplasm at regularly spaced intervals of approximately 2 micron. Electron microscopy suggested that this cytoplasmic staining was occurring in regions where substantial amounts of extended junctional SR were present. These data indicate that the DHPR codistributes with triadin and the RyR in rabbit ventricle and atrium, and furthermore suggest that some of the SR Ca2+ release channels in atrium may be activated in the absence of a close association with the DHPR.
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Canales de Calcio/aislamiento & purificación , Proteínas Portadoras , Compartimento Celular , Proteínas Musculares/aislamiento & purificación , Miocardio/ultraestructura , Animales , Canales de Calcio Tipo L , Técnica del Anticuerpo Fluorescente , Secciones por Congelación , Atrios Cardíacos/química , Atrios Cardíacos/ultraestructura , Ventrículos Cardíacos/química , Ventrículos Cardíacos/ultraestructura , Immunoblotting , Microscopía Confocal , Miocardio/química , Conejos , Canal Liberador de Calcio Receptor de Rianodina , Sarcolema/química , Sarcolema/ultraestructura , Retículo Sarcoplasmático/química , Retículo Sarcoplasmático/ultraestructuraRESUMEN
Our knowledge of the physiological and biochemical constituents of skeletal muscle excitation has increased greatly during the last few years but this has not led to a consensus of the physiological mode of muscle activation. Three hypotheses of transmission, involving either transmitter-receptor interaction or direct mechanical coupling, are still under active consideration. The hypothesis of direct mechanical coupling currently being evaluated proposes that the dihydropyridine receptor in the transverse tubules serves as a voltage sensor that communicates directly with the junctional foot protein/Ca2+ channel of sarcoplasmic reticulum to initiate opening of the channel.
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Músculos/metabolismo , Retículo Sarcoplasmático/metabolismo , Animales , Canales de Calcio/metabolismo , HumanosRESUMEN
The ectotrophic, root-infecting fungus Magnaporthe poae is the cause of summer patch of Kentucky bluegrass (Poa pratensis). The disease is widely distributed in the mid-Atlantic Region of the United States and west to central Nebraska and Kansas (2). It also has been found in certain locations of Washington and California (2) but has not been confirmed in the Rocky Mountain Region. In August 2005 and 2006, tan patches and rings of dead turf ranging from 10 to 30 cm in diameter were observed in Kentucky bluegrass swards in Grand Junction and Greeley, CO, respectively. The sites, separated by approximately 360 km, are located west and east of the Continental Divide. A network of ectotrophic hyphae were observed on diseased root segments collected from both sites. A fungus morphologically similar to M. poae (2) was consistently isolated from these segments. DNA was extracted from mycelium of one isolate from each location and amplified by PCR with the M. poae species-specific primers MP1 and MP2 (1). A 453-bp DNA fragment was consistently amplified from DNA of both isolates, diagnostic of M. poae. To our knowledge, this is the first report of summer patch in Colorado and indicates that M. poae may be widely distributed in the central Rocky Mountain Region. References: (1) T. E. Bunting et al. Phytopathology 86:398, 1996. (2) B. B. Clarke and A. B. Gould, eds. Turfgrass Patch Diseases Caused by Ectotrophic Root-Infecting Fungi. The American Phytopathological Society, St. Paul, MN, 1993.
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A procedure is proposed to optimize a high-pass filter enabling one to subtract the broadband background signals inherent in Raman spectra. A spectral approach is used to analyze the characteristics of the filter and the distortions in the processed spectra. Examples of the processing of real spectra are presented.
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Espectrometría Raman/instrumentación , Espectrometría Raman/métodos , Algoritmos , Monoterpenos Bicíclicos , Monoterpenos/análisis , Monoterpenos/química , Ricina/análisis , Ricina/químicaRESUMEN
Raman, scanning electron, and optical microscopy of hair and spectrophotometry of soluble hair proteins are used to study the effect of UV-vis radiation on white hair. The samples of a healthy subject are irradiated using a mercury lamp and compared with non-irradiated (control) hair. The cuticle damage with partial exfoliation is revealed with the aid of SEM and optical microscopy of semifine sections. Gel filtration chromatography shows that the molecular weight of soluble proteins ranges from 5 to 7kDa. Absorption spectroscopy proves an increase in amount of thiols in a heavier fraction of the soluble proteins of irradiated samples under study. Raman data indicate a decrease in the amount of SS and CS bonds in cystines and an increase in the amount of SH bonds due to irradiation. Such changes are more pronounced in peripheral regions of hair. Conformational changes of hair keratins presumably related to the cleavage of disulfide bonds, follow from variations in amide I and low-frequency Raman bands. An increase in the content of thiols in proteins revealed by both photometric data on soluble proteins and Raman microspectroscopy of hair cuts can be used to develop a protocol of the analysis of photoinduced hair modification.
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Cabello/efectos de la radiación , Compuestos de Sulfhidrilo/análisis , Rayos Ultravioleta , Cabello/química , Humanos , Microscopía Electrónica de Rastreo , Espectrometría RamanRESUMEN
Cystic fibrosis (CF) is one of the most common hereditary disorders among Caucasians. In such populations a highly prevalent mutation causing CF, delta F508, has been identified. It comprises 88% of Danish CF mutations. This mutation and five others account for 90% of all CF mutations, making carrier screening on a population basis worthy of consideration. We have therefore performed a pilot screening programme for CF carriers among pregnant women. From June 1, 1990, for the following 2 years, 6,599 women were tested: 172 were heterozygous for delta F508. Three of 162 partners tested were also heterozygous for delta F508. After genetic counselling all three couples at risk for having a child with CF requested prenatal diagnosis. One fetus was homozygous for delta F508, and the pregnancy was terminated. With currently available techniques, the screening programme presented here causes no practical problems, and screening for CF carriers can easily be run on a larger scale.
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Fibrosis Quística/genética , Tamización de Portadores Genéticos , Pruebas Genéticas/métodos , Adolescente , Adulto , Fibrosis Quística/diagnóstico , Fibrosis Quística/epidemiología , Análisis Mutacional de ADN , Dinamarca/epidemiología , Femenino , Frecuencia de los Genes , Pruebas Genéticas/economía , Humanos , Masculino , Edad Materna , Persona de Mediana Edad , Epidemiología Molecular , Proyectos Piloto , Valor Predictivo de las Pruebas , Embarazo , Embarazo de Alto Riesgo , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
The aim of the present study was to assess the impact of being identified carrier of cystic fibrosis. The impact was assessed in terms of retention of the result, sharing of the information about the result with relatives, non-relatives and GPs, changes in reproductive plans, and regrets about having been tested Three unsupervised questionnaires were sent to 160 women identified as carriers between 1990 and 1992 in June 1992, October 1993, and November 1994. Carriers freely shared the information about their result with relatives, friends, and GPs. The inconclusiveness of the test gave rise to some confusion. This may reflect inadequacies in the information and counselling given to carriers, but psychological factors are also believed to be responsible. Thus, false reassurance may be a problem in a carrier screening with a test that detect only a proportion of carriers. Few carriers considered changing their reproductive plans due to the result of the test. A few women identified as carrier regretted having had the test.
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Fibrosis Quística/psicología , Tamización de Portadores Genéticos , Fibrosis Quística/genética , Femenino , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Encuestas y CuestionariosRESUMEN
The monoclonal antibody, mAb GE 4.90, raised against triadin, a 95 kDa protein of sarcoplasmic reticulum (SR), inhibits the slow phase of Ca2+ release from SR following depolarization of the T-tubule moiety of the triad. The antibody has virtually no effect on the fast phase of depolarization-induced Ca2+ release nor on caffeine-induced Ca2+ release. Since the slow phase of depolarization-induced Ca2+ release is also inhibited by dihydropyridines (DHP), these results suggest that triadin may be involved in the functional coupling between the DHP receptor and the SR Ca2+ channel.
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Calcio/metabolismo , Proteínas Portadoras , Proteínas Musculares/metabolismo , Retículo Sarcoplasmático/metabolismo , Animales , Anticuerpos Monoclonales , Cinética , Proteínas Musculares/antagonistas & inhibidores , ConejosRESUMEN
Immunoblotting as well as enzyme assays demonstrate the presence of the self-glucosylating protein, glycogenin, in the protein-glycogen complex, in the sarcoplasmic reticulum and in phosphorylase kinase. In all three compartments glycogenin occurs in different, albeit, defined glucosylated forms, which upon deglucosylation are converted into a 42 kDa form. We suggest that phosphorylase kinase might have a dual function in glycogen biogenesis: firstly, control of glycogen degradation in the protein-glycogen complex via phosphorylation of glycogen phosphorylase b; secondly, regulation of glycogen biosynthesis on the sarcoplasmic reticular membranes via phosphorylation and thereby inhibition of glycogen synthase.
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Glucógeno/biosíntesis , Glicoproteínas/metabolismo , Músculo Esquelético/metabolismo , Fosforilasa Quinasa/metabolismo , Animales , Glucosa/metabolismo , Glucosiltransferasas , Glucógeno/química , Glucógeno Sintasa/metabolismo , Glicoproteínas/análisis , Glicoproteínas/química , Glicosilación , Peso Molecular , Músculo Esquelético/enzimología , Fosforilasa Quinasa/química , Fosforilasa b/metabolismo , Conejos , Retículo Sarcoplasmático/química , Retículo Sarcoplasmático/enzimologíaRESUMEN
OBJECTIVE: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). DESIGN AND PATIENTS: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D -3, D -2, and D -1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day DO). All patients received a continuous intravenous infusion of propofol (4.5 mg x kg(-1) x h(-1)) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. RESULTS: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 +/- 8 ml x min(-1) x kg(-1) (mean +/- SD) and 33 +/- 10 ml min(-1) x kg(-1) on D -3 and D -1, respectively, as compared to 37 +/- 11 ml x min(-1) kg(-1) and 34 +/- 8 ml x min(-1) x kg(-1) on days D + 1 and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml x min(-1) x kg(-1) and was not affected by switching from parenteral to enteral feeding. CONCLUSIONS: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol.