RESUMEN
Data on pulmonary gas exchange were collected in breathhold dives to 90 feet in a tank and in open-sea breathhold dives to depths of 217.5 and 225 feet. Thoracic blood volume displacements were measured at depths of 25, 50, 90, and 130 feet, by use of the impedance plethysmograph. The open-sea dives were carried out with an average speed of descent of 3.95 feet per second and an average rate of ascent of 3.50 feet per second. End-dive alveolar oxygen tensions did not fall below 36 millimeters of mercury, while alveolar carbon dioxide tension did not rise above 40 millimeters of mercury except in one case. These findings indicate that for diver Croft, who has unusual lung capacity, neither hypoxia nor hypercapnia determined the depth limits under those conditions. At depths of 90 and 130 feet blood was forced into the thorax, amounting to 1047 and 850 milliliters respectively.
Asunto(s)
Volumen Sanguíneo , Buceo , Alveolos Pulmonares/fisiología , Tórax/irrigación sanguínea , Adaptación Fisiológica , Adulto , Dióxido de Carbono/sangre , Diuresis , Humanos , Hipercapnia/fisiopatología , Hiperventilación/fisiopatología , Hipoxia/fisiopatología , Masculino , Oxígeno/sangre , Consumo de Oxígeno , Pletismografía de Impedancia , EspirometríaRESUMEN
A variety of N omega-monosubstituted L-arginine analogs are established inhibitors of nitric oxide synthase; in all cases, initial binding is competitive with the substrate L-arginine. The efficacy of such compounds in vivo will depend on their transport into the relevant nitric oxide synthase-containing cells; in fact, inhibition may actually be augmented if cellular uptake of L-arginine is also blocked by the analogs. Because vascular endothelial cells synthesize vasoactive nitric oxide under both physiological and pathophysiological conditions, we have performed inhibition analyses with novel arginine analogs to determine the substrate specificity of the primary L-arginine transport system. Na(+)-independent System y+, present in porcine pulmonary artery endothelial cells. As reported by others, no Na(+)-independent System bo,+ activity was detectable. For System y+. Dixon plots suggest competitive inhibition and apparent Ki values, which ranged between 0.1 and 0.8 mM, estimated for each inhibitor. Some influence of amino acid side chain structure could be detected, but in general, the data establish that this transport system accepts a broad range of arginine derivatives. Loading the cells with individual arginine analogs resulted in trans-stimulation of arginine uptake suggesting that they serve as substrates of System y+ as well as inhibitors. These results indicate that plasma membrane transport is unlikely to be a limiting factor in drug development for nitric oxide synthase inhibitors.
Asunto(s)
Arginina/análogos & derivados , Arginina/farmacología , Proteínas Portadoras/antagonistas & inhibidores , Glicoproteínas de Membrana , Proteínas de la Membrana/antagonistas & inhibidores , Óxido Nítrico Sintasa/antagonistas & inhibidores , Receptores Virales , Animales , Arginina/metabolismo , Transporte Biológico , Proteínas Portadoras/metabolismo , Células Cultivadas , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/farmacología , Proteínas de la Membrana/metabolismo , Arteria Pulmonar , PorcinosRESUMEN
The currently recommended intake of vitamin E for dairy cows is based on the prevention of nutritional myopathy, a calf disease. However, it is likely that the vitamin E requirement of the modern dairy cow is very different from that of a calf. This review of the literature investigates the effect of vitamin E supplementation on the health and fertility of the dairy cow. Supplementation of high levels of vitamin E (at least 1000 iu per day) during the dry period and early lactation can reduce the incidence of mastitis, possibly because of an increase in immune system activity and function, but there appears to be little benefit of supplementation on infectious diseases other than mastitis. The evidence for a response in the reproductive system is more equivocal. In herds with a history of selenium deficiency and a high incidence of retained fetal membranes, supplementation, in conjunction with selenium, can reduce retention, but the evidence for an effect of supplementation on other reproductive diseases, such as cystic ovarian disease and metritis, is based on a very limited number of cases. The literature suggests that the current recommendations for vitamin E are inadequate. In particular, it suggests that the current linking of requirement to dry matter intake is incorrect, because vitamin E requirement is probably at its highest when intake is at its lowest However, the majority of the data on which this conclusion is based, come from North America where cows will encounter significantly different levels of oxidative stress from cows in the EU.
Asunto(s)
Alimentación Animal , Fertilidad , Vitamina E/farmacología , Crianza de Animales Domésticos , Animales , Bovinos , Femenino , Guías como Asunto , Estado de Salud , Vitamina E/administración & dosificaciónAsunto(s)
Enzimas/metabolismo , Marcaje Isotópico/métodos , Cinética , Oxidorreductasas de Alcohol/metabolismo , Animales , Radioisótopos de Carbono , Hexoquinasa/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Hígado/enzimología , Malato Deshidrogenasa/metabolismo , Matemática , Isótopos de Oxígeno , ConejosAsunto(s)
Envejecimiento , Sistema Cardiovascular/fisiopatología , Hipertensión/diagnóstico , Pulso Arterial , Enfermedades Vasculares/diagnóstico , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Determinación de la Presión Sanguínea , Determinación del Volumen Sanguíneo , Fenómenos Fisiológicos Cardiovasculares , Humanos , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Pletismografía de ImpedanciaAsunto(s)
Arteriopatías Oclusivas/diagnóstico , Determinación de la Presión Sanguínea , Electrocardiografía , Etanol , Pletismografía , Pulso Arterial , Temperatura Cutánea , Brazo/irrigación sanguínea , Frío , Dedos/irrigación sanguínea , Frecuencia Cardíaca , Humanos , Inmersión , Pierna/irrigación sanguínea , Métodos , Pletismografía de Impedancia , Dedos del Pie/irrigación sanguíneaAsunto(s)
Etanol/farmacología , Hemodinámica/efectos de los fármacos , Nitroglicerina/farmacología , Adolescente , Adulto , Presión Sanguínea/efectos de los fármacos , Circulación Colateral , Dedos/irrigación sanguínea , Humanos , Pierna/irrigación sanguínea , Masculino , Músculos/irrigación sanguínea , Pletismografía de Impedancia , Pulso Arterial , Flujo Sanguíneo Regional/efectos de los fármacos , Piel/irrigación sanguínea , Temperatura Cutánea , Dedos del Pie/irrigación sanguínea , Resistencia Vascular/efectos de los fármacosAsunto(s)
Sistema Cardiovascular/efectos de los fármacos , Fumar/fisiopatología , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Gasto Cardíaco , Técnica de Dilución de Colorante , Electrodos , Humanos , Persona de Mediana Edad , Circulación Pulmonar/fisiología , Pulso Arterial , Piel , TemperaturaAsunto(s)
Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Etilaminas/uso terapéutico , Pierna/irrigación sanguínea , Piridinas/uso terapéutico , Trombosis/tratamiento farmacológico , Adulto , Anciano , Arteriosclerosis/complicaciones , Betahistina/uso terapéutico , Cloruros/uso terapéutico , Angiopatías Diabéticas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this appendix is to provide a brief review of issues important in the design of initial-rate assay methods.
Asunto(s)
Técnicas de Química Analítica/métodos , Biología Molecular/métodos , CinéticaRESUMEN
The purpose of this unit is to provide a brief review of issues important in the design of initial-rate assay methods. General aspects of kinetic assay design are discussed, including enzyme and substrate purity, concentration and stability. Also covered are issues such as continuous versus stop-time assay formats, coupled enzyme assays, binding studies, and presentation of initial-rate data.
Asunto(s)
Enzimas/metabolismo , Catálisis , Cinética , Unión Proteica , Especificidad por SustratoRESUMEN
Isotope exchange measurements of sheep brain glutamine synthetase have yielded conflicting experimental findings and interpretation, leaving in doubt the question of whether the enzyme operates via ordered or random pathways of enzyme-substrate interactions. We now report new experimental evidence that demonstrates the earlier discrepant results may be attributed to the choice of reaction conditions used to achieve equilibration of the chemical reaction prior to addition of isotopic tracer. A random kinetic mechanism, perhaps not of the rapid-equilibrium type, is most compatible with the exchange data. We also discuss other potential time-dependent processes that may compromise the equilibration of reaction systems and affect the outcome of exchange experiments, and criteria for equilibration are suggested for the aid of other workers.
Asunto(s)
Encéfalo/enzimología , Glutamato-Amoníaco Ligasa/metabolismo , Adenosina Difosfato , Adenosina Trifosfato , Animales , Glutamatos , Ácido Glutámico , Glutamina , Cinética , Fosfatos , OvinosRESUMEN
gamma-Glutamyl transpeptidase (purified from rat kidney) was incubated with glutathione and a mixture of amino acids that closely approximates the amino acid composition of blood plasma, and the relative extents of transpeptidation and hydrolysis were determined by quantitative measurement of the products formed (glutamate, cysteinylglycine, gamma-glutamyl amino acids). At pH 7.4, in the presence of 50 microM glutathione and the amino acid mixture, about 50% of the glutathione that was utilized participated in transpeptidation. Studies in which the formation of individual gamma-glutamyl amino acids was determined in the presence of glutathione and the amino acid mixture showed that L-cystine and L-glutamine are the most active amino acid acceptors, and that other neutral amino acids also participate in transpeptidation to a significant extent. These in vitro experiments are consistent with a number of other findings which indicate that transpeptidation is a significant physiological function of gamma-glutamyl transpeptidase.
Asunto(s)
Riñón/enzimología , Péptidos/metabolismo , gamma-Glutamiltransferasa/metabolismo , Animales , Dipéptidos/biosíntesis , Glutatión , Concentración de Iones de Hidrógeno , Cinética , Ratas , Especificidad por SustratoRESUMEN
The ATP-dependent resynthesis of tubulin from tyrosine and untyrosinated tubulin was examined to establish the most probable steady-state kinetic mechanism of the tubulin: tyrosine ligase (ADP-forming). Three pair-wise sets of initial rate experiments, involving variation of two substrates pair-wise with the third substrate held at a high (but non-saturating) level, yielded convergent-line data, a behaviour that is diagnostic for sequential mechanisms. Michaelis constants were 14 microM, 1.9 microM and 17 microM for ATP, untyrosinated tubulin and L-tyrosine respectively, and the maximal velocity was 0.2 microM/min. AMP was a competitive inhibitor with respect to ATP, and a non-competitive inhibitor versus either tubulin or tyrosine. Likewise, L-dihydroxyphenylalanine acted competitively relative to tyrosine and non-competitively with respect to either ATP or tubulin. These findings directly support a random sequential mechanism. Product inhibition patterns with ADP were also consistent with this assignment; however, inhibition studies were not practical with either orthophosphate or tyrosinated tubulin because both were very weak inhibitors. Substrate protection of the enzyme against alkylation by N-ethylmaleimide and thermal inactivation, along with evidence of enzyme binding to ATP-Sepharose and tubulin-Sepharose, also supports the idea that this three-substrate enzyme reaction exhibits a random substrate addition pathway.