Effect of silicon on creep properties of titanium 6Al-2Sn-4Zr-2Mo alloy

The alloy Ti-6Al-2Sn-4Zr-2Mo is a titanium alloy for elevated temperatures often used in aerospace applications. Minor additions of silicon have proven to improve the creep resistance of this alloy. In this work, three different amounts of silicon (0.015, 0.07 and 0.162 wt% Si) were added to cast Ti-6242 and creep tests were performed at different temperatures and loads. Creep resistance increased significantly with silicon addition by means of silicide precipitation hindering dislocations movement. Silicon rich nanoparticles in the microstructure were detected and their effect on creep resistance was investigated. The instruments used in this study were light optical microscope (LOM) and scanning electron microscopy (SEM). Precipitates larger than 150 nm were found to be located heterogeneously in the microstructure, whereas smaller precipitates, ranging from 20-100 nm were homogeneously spread in the material. All silicides were predominantly situated next to the beta-phase in the alloy, either at the prior-beta grain boundaries or the beta-phase in between the alpha-colonies

On the mechanism of stimulation of ureagenesis by gluconeogenic substrates: Role of pyruvate carboxylase

Gluconeogenic substrates, lactate or pyruvate, or ornithine produced 100% increase of urea synthesis from NH4Cl. The combined administration of ornithine and lactate (or pyruvate) produced more than additive effects, indicating that they acted at different steps in a potentiating manner. The uptake of ornithine was enhanced by gluconeogenic substrates. This finding may explain, at least in part, the stimulating effect of these substrates on ureagenesis from NH4Cl and ornithine. The gluconeogenic substrate-induced stimulation of ureagenesis from NH4Cl was still observed under conditions of reduced flux through pyruvate carboxylase, ruling out that their action was exclusively mediated by the anaplerotic effect of this enzyme. Pyruvate was a more potent stimulator of ureagenesis than lactate and its effect less sensitive to pyruvate carboxylase inhibition. These observations indicate that a correlation exists between stimulation of ureagenesis by gluconeogenic substrates and flux through pyruvate dehydrogenase. It is concluded that gluconeogenic substrates may stimulate ureagenesis from NH4Cl by 1) increasing intracellular ornithine availability and/or 2) enhancing flux through pyruvate dehydrogenase and consequently the tricarboxylic acid cycle activity.Peer reviewe

Reciprocal changes in gluconeogenesis and ureagenesis induced by fatty acid oxidation

Fatty acids produced a stimulation of gluconeogenesis and either inhibition or no effect on ureagenesis in livers perfused with gluconeogenic substrates and having NH4Cl plus ornithine as the nitrogen source. This finding indicates that stimulation of flux through pyruvate carboxylase is not sufficient to enhance urea production from ammonia. The metabolic action of fatty acids showed the following characteristics: (1) it was concentration-dependent, showing saturation-type kinetics similar to those described for fatty acid oxidation; (2) the stimulatory action on gluconeogenesis was constant and independent of NH4Cl concentration, whereas the inhibition of ureagenesis was variable and dependent on NH4Cl concentration and the degree of reduction of the gluconeogenic substrate; and (3) fatty acids produced apparent reciprocal changes in the state of reduction of the cytosolic and mitochondrial NAD systems. Fatty acid oxidation exerted its effect mainly, if not exclusively, by preventing the gluconeogenic substrate-induced stimulation of ureagenesis. Fatty acids also inhibited ureagenesis without stimulating gluconeogenesis (lactate <1 mmol/L), ruling out a limiting energy availability as the cause of the inhibition. One or both of the following two mechanisms seem to account for the fatty acid-induced inhibition of ureagenesis from NH4Cl. First, a decreased uptake of ornithine, and second, decreased flux through pyruvate dehydrogenase and probably other NAD(P)-linked mitochondrial dehydrogenases. The correlation found between the ability of fatty acids to inhibit ureagenesis and the state of activation of pyruvate dehydrogenase supports the latter point.Supported in part by grants from Dirección General de Ciencia y Tecnología (PBK7-0280), Comisión Interministerial de Ciencia y Tecnología (SAL91-0509), Comunidad de Madrid (C249190) and Fondo de Investigaciones Sanitarias (8910467 und 8910468). G.C. holds a fellowship .from the Spanish Ministerio de Educación y Ciencia. T.R. is a recipient of a fellowship from Comunidad Autónoma de Madrid

Functional coupling of Na+/H+ and Na+/Ca2+ exchangers in the alpha 1-adrenoreceptor-mediated activation of hepatic metabolism

8p.-9 fig.The purpose of this study was to characterize the role of ions other than Ca2+ in hepatic responses to alpha 1-adrenergic stimulation. We report that the alpha 1-adrenoreceptor activation of hepatic functions is accompanied by extracellular acidification and an increase in intracellular pH. These effects are dependent on extracellular Na+ concentration and are inhibited by the Na+/H+ antiporter blocker 5-(N-ethyl-N-isopropyl) amiloride under conditions that preclude antagonistic effects on agonist binding. Thus, the activation of plasma membrane Na+/H+ exchange is an essential feature of the hepatic alpha-adrenoreceptor-coupled signaling pathway. The following observations indicate that the sustained hepatic alpha 1-adrenergic actions rely on a functional coupling between the plasma membrane Na+/H+ and Na+/Ca2+ exchangers, resulting in the stimulation of Ca2+ influx. 1) Inhibition of the Na+/K(+)-ATPase does not prevent the alpha 1-adrenergic effects. However, alpha 1-adrenoreceptor stimulation fails to induce intracellular alkalinization and to acidify the extracellular medium in the absence of extracellular Ca2+. 2) A non-receptor-induced increase in intracellular Na+ concentration, caused by the ionophore monensin, stimulates Ca2+ influx and increases vascular resistance. 3) Inhibition of Na+/Ca2+ exchange prevents, in a concentration-dependent manner, most of the alpha 1-agonist-induced responses. 4) The actions of Ca(2+)-mobilizing vasoactive peptide receptors or alpha 2-adrenoreceptors, which produce neither sustained extracellular acidification nor release of Ca2+, are insensitive to Na+/H+ exchange blockers.This work was supported in part by Dirección General de Investigación Científica y Técnica Grants 87065 and PL87-0280, Plan Nacional de Investigación Científica y Técnica Grants SAL90-0766 and SAL5091/91, and Fondo de Investigaciones Sanitarias Grants 89/0467 and 891 0468.Peer reviewe

Loss of fatty acid control of gluconeogenesis and PDH complex flux in adrenalectomized rats

This work aimed to determine the role played by the adrenal gland in the fatty acid control of gluconeogenesis in isolated perfused rat livers. The gluconeogenic substrate concentration responses were not altered in adrenalectomized (ADX) rats. This observation indicates that glucocorticoids are not essential to maintain normal basal gluconeogenic rates. In contrast, fatty acid failed to stimulate gluconeogenesis from lactate and elicited attenuated stimulation with pyruvate as substrate in livers from ADX rats. Fatty acid-induced stimulation of respiration and ketone body production were similar in control and ADX rats. Thus the diminished responsiveness of the gluconeogenic pathway to fatty acid cannot be the result of different rates of energy production and/or generation of reducing power. Fatty acids did not inhibit pyruvate decarboxylation in livers from ADX rats. Even though mitochondria isolated from livers of ADX rats showed normal basal rates of pyruvate metabolism, fatty acids failed to inhibit pyruvate decarboxylation and the activity of the pyruvate dehydrogenase complex. This novel observation of the glucocorticoid effect in controlling the pyruvate dehydrogenase complex responsiveness indicates that the mitochondrial partitioning of pyruvate between carboxylation and decarboxylation reactions may be altered in livers from ADX rats. We propose that the diminished effect of fatty acid in stimulating gluconeogenesis in livers from ADX rats is the result of a limited pyruvate availability for the carboxylase reaction due to a lack of inhibition of flux through the pyruvate dehydrogenase complex.This work was supported in part by grants from Plan Nacional de Investigación Científica y Técnica (SAL 509/91 and SAF 93-0788) and Fondo de Investigaciones Sanitarias (93/0162 and 94/0224). G. Cipres and E. Urcelay were recipients of predoctoral fellowships from the Spanish Secretary of Education and Science. N. Butta was a recipient of a external fellowship from Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina

Interrelationships between ureogenesis and gluconeogensis in perfused rat liver

Stimulation of ureogenesis by ornithine and/or NH4Cl inhibited gluconeogenesis from lactate but not from equimolar concentrations of pyruvate in perfused rat liver. Neither a shortage of energy nor a decrease in α-ketoglutarate availability seems to be responsible for this inhibition. With lactate as substrate the extracellular concentration of pyruvate attained was ≊0.15 mM that assuming reflects its cytosolic concentration it would be limiting for its mitochondrial transport. Stimulation of ureogenesis from NH4Cl enhances flux through pyruvate dehydrogenase. Furthermore, activation of pyruvate dehydrogenase by dichloroacetate led to stimulation of ureogenesis and inhibition of glucose production. Conversely, inhibition of pyruvate dehydogenase flux by fatty acid enhanced glucose production and inhibited ureogenesis. Thus, ornithine and/or NH4Cl seem to inhibit lactate to glucose flux by shifting the mitochondrial partitioning of oyruvate from carboxylation towards decarboxylation with the result of a decreaased oxaloacetate formation. Gluconeogenic substrates enhanced the hepatic uptake of ornithine. However, no correlation seems to exist between the uptake of ornithine, ornithine-induced stimulation of ureogenesis and total rates of urea production. Ornithine produced a concentration-dependent acidification of the hepatic outflow perfusate, suggesting that it may be transported in exchange for H+.This work has been supported, in part, by grants from Dirección General de Ciencia y Tecnología (PB87-0280), Comisión Interministerial de Ciencia y Tecnología (SAL91-0509) and Comunidad de Madrid (C249/90). G.C. holds a fellowship from the Spanish Ministerio de Educación y Ciencia

Role of protein kinase-C in the α1-adrenoceptor-mediated responses of perfused rat liver

The present work aimed to determine the role played by protein kinase-C (PKC) in the α1-adrenoceptor-induced activation of hepatic metabolism. The following observations indicate that activation of PKC is a condition necessary for α1-adrenoceptor activation of hepatic functions, but not sufficient to mimic the receptor-mediated effects in the absence of external physiological stimuli. 1) α1-Adrenoceptor activation promoted the translocation of PKC from the cytosol to its active form in the plasma membrane. 2) Activation of PKC by the phorbol ester 12-myristate 13-acetate or exogenous diacylglycerols or by elevation of endogenous levels of diacylglycerols by inhibiting diacylglycerol kinase mimicked the α1- adrenoceptor-mediated actions. However, the time course and magnitude of the nonreceptor responses differ from those mediated by α1-adrenoceptor activation. In addition, nonreceptor-mediated activation of PKC decreased the α1-adrenoceptor responsiveness. 3) Inhibition of PKC by either H-7 [1-(5- isoquinolinilsulfonyl)2-methylpiperazine] or staurosporine inhibited all of the α1-adrenoceptor-induced responses, except gluconeogenesis. The vasopressin effects were not inhibited by H-7, indicating that PKC activation is a distinct feature of the hepatic α1-adrenoceptor activation that is not shared by all the Ca2+-mobilizing agonists. The diacylglycerol-PKC branch of the α1-adrenoceptor signaling pathway seems to control the sustained phase of stimulation of hepatic functions. In these studies we have also observed that phorbol 12-myristate 13-acetate produces a concentration- dependent inhibition of hepatic respiration. However, decreased energy availability does not seem to be the cause of its action to decrease α1- adrenoceptor responsiveness.This work was supported in part by grants from Dirección General de Investigación Científica y Técnica (87065 and PL8-0280), Plan Nacional de Investigación Científica y Técnica (SAL90-0766 y SAL509/91), and Fondo de Investigaciones Sanitarias (89/0467, 89/0468 and 93/0162). Recipient of a predoctoral fellowship from the Spanish Secretary of Education and Science. Recipient of an external fellowship from Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina