Freestream velocity-profile measurement in a large-scale, high-enthalpy reflected-shock tunnel.

ABSTRACT: We apply Krypton Tagging Velocimetry (KTV) to measure velocity profiles in the freestream of a large, national-scale high-enthalpy facility, the T5 Reflected-Shock Tunnel at Caltech. The KTV scheme utilizes two-photon excitation at 216.67 nm with a pulsed dye laser, followed by re-excitation at 769.45 nm with a continuous laser diode. Results from a nine-shot experimental campaign are presented where N 2 and air gas mixtures are doped with krypton, denoted as 99% N 2 /1% Kr, and 75% N 2 /20% O 2 /5% Kr, respectively. Flow conditions were varied through much of the T5 parameter space (reservoir enthalpy h R ≈ 5 - 16  MJ/kg). We compare our experimental freestream velocity-profile measurements to reacting, Navier-Stokes nozzle calculations with success, to within the uncertainty of the experiment. Then, we discuss some of the limitations of the present measurement technique, including quenching effects and flow luminosity; and, we present an uncertainty estimate in the freestream velocity computations that arise from the experimentally derived inputs to the code.

[An emulsion based on 1-bromoperfluorooctane: X-ray contrast properties and mechanisms of X-ray contrasting].

It has been shown that the emulsion of a mixture of the perfluorocarbons 1-bromoperfluorooctane and perfluoro[1-(4-methylcyclohexyl)piperidine], stabilized by egg yolk phospholipids, makes it possible to contrast rapidly (beginning with the 10th minute) and for a long time (up to 5 days) the tissues of various organs, such as liver, spleen, adrenal glands, heart, and the peritoneal part of the aorta. The roentgenograms of rat organs in in vivo experiments were evaluated by computer-assisted morphodensitometry. The contrasting of organs at early terms of the circulation of emulsion in the body is related to a high concentration of 1-bromoperfluorooctane in the blood flow, and the contrasting at later terms is related to the accumulation of emulsion particles by cells of the reticuloendothelial system.

[Effect of perfluorocarbon emulsions on function of enzyme systems responsible for generating active forms of oxygen in neutrophils]. / Vliianie émul'sii perftoruglerodov na funktsionirovanie fermentnykh sistem, otvetstvennykh za generatsiiu aktivnykh form kisloroda v neitrofilakh.

The ability of the emulsion of perfluoroorganic compounds stabilized with proxanol 268 to affect the functions of peritoneal neutrophils was evaluated. The functional activity of neutrophils was estimated from the intensity of generation of reactive oxygen species using the method of chemiluminescent analysis. The emulsion was shown to suppress the neutrophil responses to phorbol-12-myristate-13-acetate in a dose-dependent manner. No inhibition of the activity of neutrophils in the presence of the emulsion was observed in N-formylmethionylleucylphenylalanine stimulated cells. The data obtained indirectly confirm the suggestion that the perfluoride emulsion inhibits neutrophil NADPH oxidase activity. In the presence of the perfluoride emulsion, myeloperoxidase plays a more important role in the generation of luminescent responses in both N-formylmethionylleucylphenylalanine- and phorbol-12-myristate-13-acetate-stimulated neutrophils. The effect of perfluoride emulsion results in the preferential myeloperoxidase-produced generation of reactive oxygen species in the neutrophil respiratory burst.

[Sorption of plasma components on the surface of particles of fluorocarbon emulsions stabilized by proxanol 268]. / Sorbtsiia komponentov plazmy krovi na poverkhnosti chastits ftoruglerodnykh émul'sii, stabilizirovannykh proksanolom 268.

It was found in the experiments in vivo and in vitro that the contact of perfluorocarbon emulsion stabilized with proxanol 268 with blood plasma leads to the sorption of various plasma proteins on the surface of emulsion particles. The profile of the proteins sorbed is complex and includes proteins with molecular weights ranging from 14 to 94 kDa. Among proteins sorbed on the emulsion particles circulating in blood, IgG was identified. Incubation of the emulsion stabilized with proxanol 268 with human blood plasma in vitro was shown to result in the sorption of IgG and IgA the perfluorocarbon particles. The sorbtion of serum proteins and immune complexes circulating in blood on the surface of perfluorocarbon particles stabilized with proxanol 268 was revealed to activate the complement system.

[Mechanisms of distribution and elimination of perfluorocarbons upon multiple exposures]. / Mekhanizmy raspredeleniia i vyvedeniia perftoruglerodov pri mnogokratnykh vvedeniiakh.

In clinical practice much more often one meets a necessity of repeated administration of fluorocarbon blood substitutes. The 19F(-)-NMR-spectroscopy has been used to study the kinetics of the blood and tissue fluorocarbon concentration after repeated administration of PFC emulsion. Analysis of the data suggests that redistribution of PFCs between organs and blood after their repeated administration is under control of Ostwald ripening depending on PFC physicochemical properties (water and lipid solubility), emulsion particle diameter etc and does not connect with activity of reticuloendothelial system.

[Perfluorocarbon emulsions and other corpuscular systems influence on neutrophil activity]. / Deistvie emul'sii perftororganicheskikh soedinenii i drugikh korpuskuliarnykh sred na aktivnost' neitrofilov.

Influence of perfluorodecalin, perfluoromethilcyclohexylpiperidine, perfluorotributylamine emulsions on active oxygen form (AOF) generation by neutrophils has been studied. All investigated emulsions stabilized both proxanol 268 and egg yolk phospholipids inhibited PMA-stimulated neutrophil activity. Castor oil emulsion also inhibited the neutrophil activity. Neutrophil response for chemotactic peptide, was unchanged in the presence of all tested emulsions. We suppose that fast hydrophobic attachment of inert submicrone emulsion particles to cell surface provokes alteration of neutrophil plasma membrane function resulting in a decrease of AOF generation.

[Uncoupling of the liver monooxygenase system by perfluorocarbons in vivo]. / Razobshchenie monoksigenaznoi sistemy pecheni perftoruglerodami in vivo.

Administration of a perfluorodecalin (PFD) emulsion, the liver cytochrome P-450 II B1/B2 inducer, to experimental animals is followed by a two-fold increase of the NADPH oxidation rate in liver microsomes. This phenomenon is caused by the presence in the cytochrome P-450 active center of PFD which uncouples microsomal hydroxylation. The high rate of NADPH oxidation in liver microsomes after administration of the fluorocarbon does not decrease the level of reduced pyridine nucleotides in the liver and does not change the glucose concentration in the plasma. It is suggested that the accelerated weight loss in starved animals following PFD administration is due to the energy dissipation in the fluorocarbon uncoupled monooxygenase reactions in the liver.

[Interaction of perfluoroctylbromide with liver microsomal monooxygenase]. / Vzaimodeistvie perftorktilbromida s mikrosamal'noi monoksigenazoi pecheni.

Perfluorooctylbromide (PFOB), a constituent component of gas-transporting fluorocarbon emulsions, liberates bromide ions when PFOB undergoes NADPH-dependent metabolism by liver microsomal monooxygenase. The PFOB emulsion injected to rats decreases the liver microsomal cytochrome P-450 level down to 80% of control. Induction of the "phenobarbital" isoforms of cytochrome P-450 (cytochrome P-450 II B1/B2) after administration of PFOB is much weaker than that after administration of the perfluorodecalin emulsion. It is suggested that the anomalous cytochrome P-450-inductive properties of PFOB may be associated with its ability to be metabolized by liver microsomal monooxygenase. In these terms, the generally accepted viewpoint about the biological inertness and unchangeability within the organism of perfluorochemicals containing heteroatoms (N, O, H and others) and double bonds, needs further verification and experiment.

[Mechanism of inhibiting the cytochrome P-450-dependent monooxygenase system in liver with fluorocarbons]. / Mekhanizm ingibirovaniia tsitokhrom P-450-zavisimoi monooksigenaznoi sistemy pecheni ftoruglerodami.

The inducer of the liver monooxygenase system perfluorodecalin added to microsomes as a submicron emulsion forms an enzyme-substrate complex with cytochrome P-450. The K(app) values for the perfluorodecalin binding to cytochrome P-450 in microsomes isolated from the livers of control and phenobarbital-treated rats are 5 x 10(-5) M and 2.3 x 10(-6) M, respectively. Perfluorodecalin competitively inhibits the binding of substrates to cytochrome P-450 and decreases the rates of monooxygenase reactions. Perfluorodecalin extrusion from the active center of cytochrome P-450 occurs when an excess of perfluorocarbons non-interacting with cytochrome P-450 is added to microsomes. There is a significant vagueness in the rates of various monooxygenase reactions because of simultaneous induction and inhibition of monooxygenase enzymes after perfluorodecalin administration to rats. The data obtained are consistent with the hypothesis that constitutive forms of cytochrome P-450 are primary receptors for xenobiotic-inducers of phenobarbital-type cytochrome P-450 isoforms.

Effect of perfluorodecalin on activities of hepatic phase II xenobiotic biotransformation enzymes.

The activity of the hepatic phase II enzymes of xenobiotic biotransformation after intravenous administration of perfluorodecalin emulsion to rats was measured. Perfluorodecalin was found to increase the microsomal glutathione S-transferase and UDP-glucuronosyltransferase activities 1.4- and 2.3-fold, respectively. The activity of sulphotransferase was decreased 2-fold. These results show that perfluorodecalin is an inducer of both the enzymes of cytochrome P-450-dependent monooxygenase system [Mishin V. et al (1989) Chem.-Biol. Interactions, 72, 143-155.] and those catalyzing conjugation reactions: microsomal glutathione S-transferase and UDP-glucuronosyltransferase.

[The effect of perfluordecaline on the activity of phase III xenobiotic transformation enzymes]. / Vliianie perftordekalina na aktivnost' fermentov II fazy biotransformatsii ksenobiotikov.

Injection of perfluorodecaline to rats caused an increase of the phase II xenobiotic biotransformation enzyme activities followed by cytochrome P-450 induction. The activities of liver microsomal UDP-glucuronosyl transferase and glutathione transferase increased by 130 and 40%, respectively, against the control level. The increase of the cytosolic glutathione transferase activity was insignificant In contrast, the activity of sulfotransferase decreased about 2-fold. The role of modification of xenobiotic biotransformation enzymes in the biological effect of perfluorodecaline is discussed.

The phenobarbital-type induction of rat liver microsomal monooxygenases by perfluorodecalin.

Induction of perfluorodecalin (PFD) of the liver microsomal system of metabolism of xenobiotics has been studied and compared with the inductions by phenobarbital (PB) and 3-methylcholanthrene (MC). It has been shown that PFD increases the content of cytochrome P-450, NADPH-cytochrome c reductase activity. Like PB, PFD induces the activities of benzphetamine-N-demethylase, aldrine-epoxidase, 16 beta-androstendion-hydroxylase. Using specific antibodies against cytochromes P-450b and P-450c (which are the main isoenzymes of cytochrome P-450 in the PB- and MC-microsomes respectively), an immunological identity of the cytochrome P-450 isoforms during PFD and PB induction has been found. According to the rocket immunoelectrophoresis the content of cytochrome P-450 in PFD-microsomes, which is immunologically indistinguishable from P-450b, was approximately 70% of the total cytochrome P-450. Two forms of cytochrome P-450 were isolated from the liver microsomes of PFD-induced rats and purified to homogeneity. A comparison of these forms with cytochromes P-450b and P-450e obtained from the PB-induced rat liver microsomes revealed their similarity in a number of properties, e.g., chromotographic behavior on DEAE-Sephacel column, molecular weight determined by sodium dodecyl sulphate (SDS) electrophoresis in polyacrylamide gel, immunoreactivity, peptide mapping, catalytic activity. The data presented demonstrate that PFD induced in rat liver microsomes the cytochrome P-450 forms whose immunological properties and substrate specificity correspond to those of the PB-type cytochrome P-450. These findings suggest that PFD and PB, which differ in their chemical structure, induce in the rat liver microsomes identical forms of cytochrome P-450.

[Perfluorocarbons do not induce cytochrome P-448 in the rat liver]. / Perftororganicheskie soedineniia ne indutsiruiut obrazovaniia tsitokhroma P-448 v pecheni krys.

Cytochrome P-450 forms appearing in the liver after injection of methylcholanthrene, polychlorinated biphenyls and perfluorochemical emulsion to rats were studied. Activities of marker enzymes, benzpyrenehydroxylase and 7-ethoxyresorufin-O-deethylase, as well as the interaction of liver microsomal membranes with antibodies against different cytochrome forms were investigated. It was shown that fluorocarbon emulsion containing perfluorodecalin did not induce cytochrome P-448 in the rat liver.

[Analysis of the physico-chemical properties of fluorocarbon inducers of cytochrome P-450 in membranes of liver endoplasmic reticulum]. / Analiz fiziko-khimicheskikh svoistv ftoruglerodnykh induktorov tsitokhroma P-450 v membranakh éndoplazmaticheskogo retikuluma pecheni.

Cytochrome P-450 induction in rat liver microsomes after intravenous injections of submicrone emulsions of nine perfluorochemicals (2 g of PFC per kg of body weight) was investigated. A comparison of physico-chemical properties of the fluorocarbons revealed that their activity as cytochrome P-450 inducers is determined by their solubility in H2O and lipids as well as by the pressure of their saturated vapours at 37 degrees C. The fluorocarbons capable of inducing cytochrome P-450 have a molecular mass of 400-550 Da. The presence of heteroatoms (N and O) and some structural peculiarities of the perfluorochemicals do not influence the ability of the fluorocarbons to induce cytochrome P-450.

[Phenobarbital-type induction of cytochrome P-450 in liver microsomes by perfluorodecalin]. / Fenobarbitalovyi tip induktsii tsitokhroma P-450 mikrosom pecheni perftordekalinom.

Cytochrome P-450 induction in hepatic microsomes after injections of rats with a fluorocarbon emulsion containing perfluorodecalin was studied in comparison with phenobarbital and methylcholanthrene type inductions. It was shown that perfluorodecalin injection as well as the phenobarbital one cause an increase in the cytochrome P-450 content, NADPH-cytochrome c reductase activity, the rates of benzphetamine N-demethylation and aldrin epoxidation in the microsomes. Using the Ouchterlony double immunodiffusion test with antibodies against cytochrome P-450b, an immunological identity of cytochrome P-450 isoforms during perfluorodecalin and phenobarbital inductions was shown. Upon "rocket" immunoelectrophoresis the recovery of cytochrome P-450 which is immunologically indistinguishable from cytochrome P-450b was approximately 72% in perfluorodecalin-induced microsomes. The activity of benzphetamine demethylase and aldrin epoxidase was inhibited by antibodies against cytochrome P-450b. These results suggest that in rat hepatic microsomes perfluorodecalin induces the cytochrome P-450 isoform whose immunological properties and substrate specificity correspond to those of phenobarbital-type cytochrome P-450.

[Induction of microsomal cytochromes in the rat liver after intravenous administration of emulsions of perfluoro-organic compounds]. / Induktsiia mikrosomal'nykh tsitokhromov v pecheni krys posle vnutrivennogo vvedeniia zhivotnym émul'sii perftoroorganicheskikh soedinenii.

Intravenous injections of perfluoroorganic emulsions to rats in a dose of 3 ml/kg led to changes in the composition and activity of enzymes of the liver microsomal membrane monooxygenase system. At the peak of induction, i. e., on the 3rd post-injection day, the levels of microsomal cytochromes P-450 and b5 increased 2.8- and 1.9-fold, respectively, as compared to the control. Simultaneously, the rate of NADPH oxidation in the microsomes and the rate of hydroxylation of substrates I and II showed an increase. Conversely, the rate of NADPH-dependent peroxidation of microsomal lipids on the 2nd-4th post-injection days reached its minimal values. These injections stimulated the detoxicating function of rat liver as evidenced from the duration of the hexenal sleep of the animals. All the changes in the monooxygenase system parameters were temporary and reached the control level on the 10th-14th days after injection. It was demonstrated that the main component of the perfluoroorganic emulsions, perfluorodecalin, was responsible for the induction of the monooxygenase system enzymes.