RESUMEN
When guinea pigs are fed tissue-saturating amounts of ascorbate, C1q concentrations are significantly higher than in those animals fed only enough ascorbate for adequate growth and for the prevention of scurvy. C1q is the recognition protein of the classical complement pathway, a system of blood proteins that constitutes an important part of host defense against pathogens. The observed effect of ascorbate nutriture on C1q concentrations is consistent with the known role of ascorbic acid in hydroxyproline biosynthesis. C1q is a hydroxyproline-containing protein with structural similarities to collagen.
Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Ácido Ascórbico/farmacología , Complemento C1q/metabolismo , Análisis de Varianza , Animales , Cobayas , Hidroxiprolina/sangre , Inmunodifusión , MasculinoRESUMEN
Control of pilot workload may prevent performance failure of VRF pilots in adverse weather. Measurement of workload and the prediction of performance failure are the first steps. Twelve low-time non-instrument rated pilots were progressively tasked with flight maneuvers under simulated instrument meteorological conditions to the point of performance failure. For each of 3 simulated flights, 14 maneuvers, presented in groups, were performed. Perceived workload was reported by the Subjective Workload Assessment Technique. We obtained 500 workload scores. Workload scores varied significantly between the groups of maneuvers. Instrument landing system approaches had the highest workloads, with descents the second highest. Workload scores were significantly higher when associated with performance failure. The Subjective Workload Assessment Technique proved to be a sensitive workload measure. It showed some promise as a predictor of performance breakdown.
Asunto(s)
Medicina Aeroespacial , Trabajo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Percepción , Estrés PsicológicoRESUMEN
This study shows that guinea pigs fed 100 times the amount of vitamin C needed for growth and for prevention of scurvy have elevated levels of complement component C1q. C1q is a plasma protein rich in hydroxyproline, an amino acid whose biosynthesis requires ascorbate. C1q is essential for host defense against pathogens, both as a component of the classical complement pathway and as an opsonin in the phagocytosis process. We measured C1q in vitamin C-depleted guinea pigs that had been repleted for 4 wks with the following daily doses of ascorbate (mg/100 g body wt): 0.50 (suboptimal), 2.0 (adequate), 10 (ample) and 50 (tissue saturating). We measured C1q in three ways: indirectly by quantifying protein-bound hydroxyproline and directly by hemolytic assay and by immunodiffusion against anti-C1q. Regardless of the method, plasma C1q was 30-50% higher in animals fed tissue-saturating ascorbate than in those fed adequate or suboptimal amounts of the vitamin (p less than 0.05, one-way analysis of variance, least significant difference test). These data confirm and significantly extend earlier work that provided indirect evidence for a relationship between C1q and ascorbate nutriture in the guinea pig. They are consistent with a possible relationship between ascorbate nutriture and host defense.
Asunto(s)
Ácido Ascórbico/administración & dosificación , Enzimas Activadoras de Complemento/biosíntesis , Complemento C1/biosíntesis , Animales , Ácido Ascórbico/inmunología , Complemento C1q , Cobayas , Hidroxiprolina/metabolismo , Inmunodifusión , Masculino , Estado NutricionalRESUMEN
Retinoic acid (RA), a naturally occurring metabolite of vitamin A, increased the number of receptors for nerve growth factor (NGF) in cultured human neuroblastoma cells (LA-N-1), as indicated by an immunofluorescence assay of cell surface receptors and by specific binding of 125I-NGF to solubilized receptors. Analysis of 125I-NGF binding showed that RA increased the number of both high affinity and low affinity receptors for NGF without affecting the equilibrium dissociation constants. Neurite outgrowth similar to that produced by NGF occurred following RA-treatment in LA-N-1 cells, in the SY5Y subclone of SK-N-SH human neuroblastoma cells and in explanted chick dorsal root ganglia (DRG). Whether morphological changes following RA treatment are directly related to the increase in NGF receptors is unknown. Data presented here are consistent with literature reports that RA modifies cell surface glycoproteins, including those that act as cell surface receptors for epidermal growth factor and insulin.
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Factores de Crecimiento Nervioso/metabolismo , Receptores de Superficie Celular/metabolismo , Tretinoina/farmacología , Línea Celular , Membrana Celular/metabolismo , Humanos , Factores de Crecimiento Nervioso/farmacología , Neuroblastoma/metabolismo , Neuroblastoma/patología , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Factor de Crecimiento NerviosoRESUMEN
This paper provides indirect evidence that ascorbate nutriture affects plasma concentrations of complement component C1q in the guinea pig. C1q is a protein with a hydroxyproline-rich region similar in structure to collagen. It is essential for complement-mediated lysis of pathogens and may also facilitate phagocytic activity of macrophages and neutrophils. Since C1q is the only hydroxyproline-containing protein in the euglobulin fraction of plasma, it can be quantified indirectly by precipitating this fraction, hydrolyzing it and estimating hydroxyproline colorimetrically. We investigated the effect of ascorbate nutriture on protein-bound hydroxyproline (PBH) in the euglobulin fraction of plasma of young male guinea pigs. The animals had been depleted of ascorbate for 3 wk to produce scurvy and then repleted (6 wk) as follows: 0.5, 2.0 and 10.0 mg ascorbate/100 g body weight per d or 10 g ascorbate per liter of drinking water. PBH values were significantly correlated (P less than 0.001) with dietary ascorbate (+ 0.74) and with liver ascorbate (+ 0.75). Plasma PBH was significantly higher (P less than 0.01, Scheffé's test) in guinea pigs fed ample ascorbate (10.0 mg/100 g body weight per day) or tissue-saturating levels (10 g/L of drinking water) than in those fed adequate (2.0 mg/100 g body weight) or suboptimal (0.5 mg/100 g body weight) levels. These data are consistent with the known biochemical role of ascorbic acid in hydroxyproline biosynthesis and suggest a possible link between ascorbate and the immune response via C1q.
Asunto(s)
Deficiencia de Ácido Ascórbico/sangre , Ácido Ascórbico/farmacología , Proteínas Sanguíneas/metabolismo , Hidroxiprolina/sangre , Animales , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/metabolismo , Enzimas Activadoras de Complemento/sangre , Complemento C1q , Dieta , Cobayas , Hígado/metabolismo , MasculinoRESUMEN
Although it is well established that the requirement for vitamin B-6 is increased by high levels of dietary protein, little is known regarding the effect of protein quality on this requirement. We therefore compared the effect on vitamin B-6 status of diets containing amino acid mixtures equivalent to low quality (LQ) or good quality (GQ) protein. The effect of protein quality was tested at two levels of vitamin B-6, 0.2 and 7.0 mg/kg diet. Food intake was controlled by pair-feeding so that no statistically significant difference in food intake existed among the groups. After 6 weeks, vitamin B-6 status was evaluated by determining urinary 4-pyridoxic acid, plasma pyridoxal phosphate and total vitamin B-6 in liver. At both levels of vitamin B-6 intake, mean values for all three indices of vitamin B-6 status were lower in rats fed LQ protein than in rats fed GQ protein, but these differences were not statistically significant (Scheffé's multiple-range test). However, a strong and highly significant linear relationship (P less than 0.0001) existed between the mean values for each parameter of vitamin B-6 status and protein quality--specifically, LQ protein appeared to have an adverse effect on vitamin B-6 status of rats fed either suboptimal or ample vitamin B-6. These results suggest a minor but consistent deleterious effect of LQ protein on vitamin B-6 status in rats, regardless of vitamin B-6 intake.
Asunto(s)
Aminoácidos/farmacología , Proteínas en la Dieta/farmacología , Hígado/efectos de los fármacos , Piridoxina/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal/efectos de los fármacos , Hígado/metabolismo , Masculino , Tamaño de los Órganos , Fosfato de Piridoxal/sangre , RatasRESUMEN
Valine deficiency in rats produced motor incoordination attributable to selective damage to the red nuclei, midbrain structures that modulate motor activity. Neither incoordination nor red nuclei damage occurs in rats deprived of valine, isoleucine and leucine, thus suggesting that valine neurotoxicity results from amino acid imbalance rather than from lack of valine per se. To explore this possibility, we compared neutral amino acid patterns in plasma and brain of rats fed for 7 days a complete diet fed ad libitum or pair-fed, a valine-free diet or a diet lacking in all three essential branched-chain amino acids (BCAA). Statistical evaluation showed that plasma valine in valine-deprived rats was lower (P less than 0.01) than in pair-fed and ad libitum-fed controls but did not differ from rats lacking BCAA. Brain valine in valine-deprived rats did not differ from ad libitum-fed controls and actually was higher (P less than 0.01) than in pair-fed and BCAA-deprived rats. The most striking changes seen in the amino acid pattern of valine-deprived rats as compared to all other groups were in the increased leucine:valine ratio (P less than 0.01 for plasma and brain) and in the increased leucine + isoleucine:valine ratio (P less than 0.01 plasma; P less than 0.001, brain). These results are consistent with the view that amino acid imbalance is a critical factor in the development of the neurotoxicity of valine deficiency.
Asunto(s)
Aminoácidos/metabolismo , Encéfalo/metabolismo , Valina/deficiencia , Aminoácidos/sangre , Aminoácidos de Cadena Ramificada/metabolismo , Animales , Peso Corporal , Encéfalo/patología , Concentración de Iones de Hidrógeno , Cetoácidos/sangre , Masculino , Ratas , Ratas EndogámicasRESUMEN
Prolonged oral administration of the Lathyrus sativus neurotoxin, L-3-oxalylamino-2-aminopropionic acid (OAP), to three young male squirrel monkeys at dose rates of 0.6 to 6.0 mg/g body weight/day produced no neurologic signs and no adverse effects other than depressed activity and occasional foaming at the mouth. When the dose was increased to 8.0 to 8.5 mg/kg body weight/day in two animals, seizures and death occurred after 3 and 5 days. The signs were typical of acute OAP intoxication observed previously to occur in the squirrel monkey within an hour after a single ip dose (2 mg/g body weight) of OAP. Total cumulative dosage of OAP and duration of the experiments were as follows: Experiment 1, 9.5 g, 38 days; Experiment 2, 157 g, 178 days; Experiment 3, 64 g, 33 days. Histologic examination revealed no abnormalities in brain, spinal cord, or other organs. These experiments suggest that the adult squirrel monkey is highly resistant to chronic oral OAP intoxication. Under our experimental conditions, this species did not provide a satisfactory animal model for human neurolathyrism, a disease postulated to result from chronic OAP intoxication.
Asunto(s)
Aminoácidos Diaminos/toxicidad , Neurotoxinas/administración & dosificación , Administración Oral , Aminoácidos Diaminos/administración & dosificación , Animales , Esquema de Medicación , Resistencia a Medicamentos , Masculino , SaimiriAsunto(s)
Enfermedades del Sistema Nervioso/inducido químicamente , Administración Oral , Envejecimiento , Aminoácidos Diaminos/administración & dosificación , Aminoácidos Diaminos/metabolismo , Animales , Encéfalo/metabolismo , Inyecciones Intraperitoneales , Dosificación Letal Mediana , Masculino , Ratones , Factores de Tiempo , Distribución TisularRESUMEN
When valine, an essential amino acid, was withdrawn from the diet of weanling rats, the animals rapidly developed a unique pattern of neurological symptoms characterized by head retraction, staggering and aimless circling. At necropsy degenerative changes were most prominent in the neurons of the red nuclei, brain stem structures which modulate motor function. To explore the pathogenesis of the neurotoxicity associated with valine deficiency, we fed rats purified diets deficient in valine alone or in valine plus other branched chain and neutral amino acids, and we examined brain tissues by light microscopy. Motor disfunction and red nuclei damage occurred only in rats fed diets lacking valine alone and not in rats fed diets lacking all three branched chain amino acids. These results suggest that the neurotoxicity of valine deficiency results from amino acid imbalance rather than from lack of dietary valine per se.