PIV quantification of the flow induced by an ultrasonic horn and numerical modeling of the flow and related processing times.

The flow in a confined container induced by an ultrasonic horn is measured by Particle Image Velocimetry (PIV). This flow is caused by acoustic streaming and highly influenced by the presence of cavitation. The jet-like experimentally observed flow is compared with the available theoretical solution for a turbulent free round jet. The similarity between both flows enables a simplified numerical model to be made, whilst the phenomenon is very difficult to simulate otherwise. The numerical model requires only two parameters, i.e. the flow momentum and turbulent kinetic energy at the position of the horn tip. The simulated flow is used as a basis for the calculation of the time required for the entire liquid volume to pass through the active cavitation region.

The development of truncated inviscid turbulence and the Fermi-Pasta-Ulam problem.

A study was made of the possible similarity between the development of truncated, inviscid turbulence and the Fermi-Pasta-Ulam (FPU) problem. For the case of a constant time scale, which resembles the FPU problem, a significant increase in the time to achieve equipartition was found when the initial energy was decreased. At first a few modes were generated and only rather late in the spectral development other modes appear and equipartition was established.

Antioxidant mechanisms of isoflavones in lipid systems: paradoxical effects of peroxyl radical scavenging.

Oxidation of lipids has been implicated in the pathophysiology of atherosclerosis. It has been suggested that scavenging of lipid peroxyl radicals contribute to the antiatherosclerotic effects of naturally occurring compounds such as the isoflavones. This group of polyphenolics includes genistein and is present in relatively high concentrations in food products containing soy. Soy isoflavones are capable of inhibiting lipoprotein oxidation in vitro and suppressing formation of plasma lipid oxidation products in vivo. However, key aspects of the antioxidant mechanisms remain unknown. In this study the antioxidant effects of genistein and other soy isoflavones on lipid peroxidation initiated by mechanistically diverse oxidants was investigated. Although isoflavones inhibited lipid peroxidation stimulated by both metal-dependent and independent processes, the concentration required for these effects were relatively high compared to those found in vivo. Interestingly, however, isoflavones were not consumed and remained in the native state over the time during which inhibition of lipid peroxidation was observed. This was also the case under conditions where synergistic inhibition of LDL oxidation was observed with ascorbate. Furthermore, in an oxidation system driven solely by peroxyl radicals, isoflavones were found to be relatively poor peroxyl radical scavengers. Consistent with the apparent lack of reactivity with lipid-derived oxidants, isoflavones were also relatively resistant to oxidation mediated by the potent oxidant peroxynitrite. The potential antioxidant mechanisms of isoflavones are discussed in the context of possible reactivities of isoflavone-derived phenoxyl radicals.

Soy isoflavonoids and cancer -- metabolism at the target site.

Isoflavonoids are members of the broad class of plant polyphenols that have been shown in vivo to have benefit in the prevention of a wide variety of chronic diseases, including cancer. For genistein (5,7,4'-trihydroxyisoflavone) (GEN), the major isoflavone in soy, reported mechanisms for these biological activities are numerous and include regulation of estrogen-mediated events, inhibition of tyrosine kinase and DNA topoisomerase activities, synthesis and release of TGF beta, and modulation of apoptosis. However, the biochemical effects of GEN in cell culture occur at concentrations in the micromolar range, far above the circulating levels of the unconjugated GEN. This may point to the limitations of cell culture for the evaluation of the activity and mechanisms of potential anti-carcinogens. GEN is extensively metabolized in vivo, with only about 14-16% excreted in an unmodified form. Metabolism may also occur because of interaction between GEN (as well as other polyphenols) and oxidants produced by inflammatory cells (HOCl, HOBr and ONOO(-)). These react with GEN to form brominated, chlorinated and/or nitrated GEN. Emerging evidence indicates that these modifications may substantially increase the biological activities of the parent compound. Future investigations of GEN and other polyphenols must, therefore, take into account metabolism at the tissue site.

Enhanced antioxidant activity after chlorination of quercetin by hypochlorous acid.

BACKGROUND: Several epidemiological studies indicate that moderate consumption of red wine decreases both the incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are polyphenols present in relatively large concentrations in red wine and may play a role in this cardioprotective phenomenon. The precise mechanisms of cardioprotection remain unclear but may involve the action of these polyphenols as antioxidants, which attenuate the tissue injury that results from the production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction products by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates were detected for both quercetin and the glycoside derivative, rutin, which suggests that both the conjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants toward oxidative modification of low-density lipoproteins and ABTS radical formation than the unmodified form. CONCLUSIONS: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated derivates, which exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.

Formation of novel bioactive metabolites from the reactions of pro-inflammatory oxidants with polyphenolics.

Dietary polyphenolics such as those in soy or red wine can have beneficial effects on the development of chronic human diseases. The mechanisms of action of isoflavones have been diverse and include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as antioxidants. Recent insights into the oxidative stress model of atherosclerosis suggest an interesting synthesis of these concepts. Sites of inflammation are associated with the formation of complex mixtures of reactive oxygen, nitrogen and halogenating species capable of modifying both endogenous biomolecules and polyphenolics. Of particular significance are the halogenation reactions mediated by myeloperoxidase that can modify key amino acids such as arginine and polyphenolics such as genistein. Hypochlorite, the reaction product of myeloperoxidase can halogenate polyphenolics to form stable derivatives with modified biological activity. Thus the in situ metabolism at sites of inflammation is unique and generates novel pharmacophores with potentially distinct modes of action from the parent compounds.

Chlorination and nitration of soy isoflavones.

Diets enriched in soy foods containing a high concentration of isoflavonoids are associated with a decrease in the incidence of several chronic inflammatory diseases. Studies with experimental models of diseases, such as atherosclerosis, suggest that these effects can be ascribed to the biological properties of the isoflavones. Since the isoflavones and tyrosine have structural similarities and modifications to tyrosine by inflammatory oxidants such as hypochlorous acid (HOCl) and peroxynitrite (ONOO(-)) have been recently recognized, we hypothesized that the isoflavones also react with HOCl and ONOO(-). Using an in vitro approach, we demonstrate in the present study that the isoflavones genistein, daidzein, and biochanin-A can be chlorinated and nitrated by these oxidants. These reactions were investigated using high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. In the reaction with HOCl, both mono- and dichlorinated derivatives of genistein and biochanin-A are formed, whereas with daidzein only a monochlorinated derivative was detected. The reaction between genistein or daidzein and ONOO(-) yielded a mononitrated product. However, no nitrated product was detected with biochanin-A. Furthermore, the reaction between genistein and sodium nitrite and HOCl yielded a chloronitrogenistein derivative, as well as a dichloronitrogenistein derivative. These results indicate that the ability of the isoflavones to react with these oxidant species depends on their structure and suggest that they could be formed under conditions where these reactive species are generated under pathological conditions.