Nonlinear measures of QT interval series: novel indices of cardiac repolarization lability: MEDqthr and LLEqthr

In this study, we investigated nonlinear measures of chaos of QT interval time series in 28 normal control subjects, 36 patients with panic disorder and 18 patients with major depression in supine and standing postures. We obtained the minimum embedding dimension (MED) and the largest Lyapunov exponent (LLE) of instantaneous heart rate (HR) and QT interval series. MED quantifies the system's complexity and LLE predictability. There was a significantly lower MED and a significantly increased LLE of QT interval time series in patients. Most importantly, nonlinear indices of QT/HR time series, MEDqthr (MED of QT/HR) and LLEqthr (LLE of QT/HR), were highly significantly different between controls and both patient groups in either posture. Results remained the same even after adjusting for age. The increased LLE of QT interval time, series in patients with anxiety and depression is in line with our previous findings of higher QTvi (QT variability index, a log ratio of QT variability corrected for mean QT squared divided by heart rate variability corrected for mean heart rate squared) in these patients, using linear techniques. Increased LLEqthr (LLE of QT/HR) may be a more sensitive tool to study cardiac repolarization and a valuable addition to the time domain measures such as QTvi. This is especially important in light of the finding that LLEqthr correlated poorly and nonsignificantly with QTvi. These findings suggest an increase in relative cardiac sympathetic activity and a decrease in certain aspects of cardiac vagal function in patients with anxiety as well as depression. The lack of correlation between QTvi and LLEqthr suggests that this nonlinear index is a valuable addition to the linear measures. These findings may also help to explain the higher incidence of cardiovascular mortality in patients with anxiety and depressive disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Metal speciation dynamics in colloidal ligand dispersions. Part 3: Lability features of steady-state systems

A lability criterion is developed for dynamic metal binding by colloidal ligands with convective diffusion as the dominant mode of mass transport. Scanned stripping chronopotentiometric measurements of Pb(II) and Cd(II) binding by carboxylated latex core-shell particles were in good agreement with the predicted values. The dynamic features of metal ion binding by these particles illustrate that the conventional approach of assuming a smeared-out homogeneous ligand distribution overestimates the lability of a colloidal ligand system. Due to the nature of the spatial distribution of the binding sites, the change in lability of a metal species with changing ligand concentration depends on whether the ligand concentration is varied via manipulation of the pH (degree of protonation) or via the particle concentration. In the former case the local ligand density varies, whereas in the latter case it is constant. This feature provides a useful diagnostic tool for the presence of geometrically constrained binding sites.

Metal speciation dynamics in colloidal ligand dispersions. Part 2: electrochemical lability

We investigate the dynamic nature of metal speciation in colloidal dispersions using a recently proposed theory [J.P. Pinheiro, M. Minor, H.P. Van Leeuwen, Langmuir, 21 (2005) 8635] for complexing ligands that are situated on the surface of the particles. The new approach effectively modifies the finite rates of association/dissociation of the colloidal metal complexes, thus invoking consideration of the two basic dynamic criteria: the association/dissociation kinetics of the volume complexation reaction (the ‘‘dynamic’’ criterion), and the interfacial flux of free metal to a macroscopic surface due to dissociation of complex species (the ‘‘lability’’ criterion). We demonstrate that the conventional approach for homogeneous systems that assume a smeared-out ligand distribution, overestimates both the dynamics and the lability of metal complexes when applied to colloidal ligands. It is also shown that the increase of lability with increasing particle radius, as expected for a homogeneous solution, is moderated for spherical microelectrodes and practically eliminated for planar electrodes.

The polychaete worm Nereis diversicolor increases mercury lability and methylation in intertidal mudflats

The polychaete worm Nereis diversicolor engineers its environment by creating oxygenated burrows in anoxic intertidal sediments. The authors carried out a laboratory microcosm experiment to test the impact of polychaete burrowing and feeding activity on the lability and methylation of mercury in sediments from the Bay of Fundy, Canada. The concentration of labile inorganic mercury and methylmercury in burrow walls was elevated compared to worm-free sediments. Mucus secretions and organic detritus in worm burrows increased labile mercury concentrations. Worms decreased sulfide concentrations, which increased Hg bioavailability to sulfate-reducing bacteria and increased methylmercury concentrations in burrow linings. Because the walls of polychaete burrows have a greater interaction with organisms, and the overlying water, the concentrations of mercury and methylmercury they contain is more toxicologically relevant to the base of a coastal food web than bulk samples. The authors recommend that researchers examining Hg in marine environments account for sediment dwelling invertebrate activity to more fully assess mercury bioavailability.

Lability of Cd, Cr, Cu, Mn and Pb complexed by aquatic humic substances

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lability of heavy metal species in aquatic humic substances characterized by ion exchange with cellulose phosphate

Labile metal species in aquatic humic substances (HSs) were characterized by ion exchange on cellulose phosphate (CellPhos) by applying an optimized batch procedure. The HSs investigated were pre-extracted from humic-rich waters by ultrafiltration and a resin XAD 8 procedure. The HS-metal species studied were formed by complexation with Cd(II), Ni(II), Cu(II), Mn(II) and Pb(II) as a function of time and the ratio ions to HSs. The kinetics and reaction order of this exchange process were studied. At the beginning (<3 min), the labile metal fractions are separated relatively quickly. After 3 min, the separation of the metal ions proceeds with uniform half-lives of about 12-14 min, revealing rather slow first-order kinetics. The metal exchange between HSs and CellPhos exhibited the following order of metal lability with the studied HSs: Cu > Pb > Mn > Ni > Cd. The required metal determinations were carried out by atomic absorption spectrometry.

Relative lability of trace metals complexed in aquatic humic substances using ion-exchanger cellulose-hyphan

The purpose of this paper is to characterize the lability/inertness metal fractions complexed by aquatic humic substances (HS) in relation to pH, complexation time, and HS concentration. HS were preconcentrated by ultrafiltration and complexed with bivalent metal ions. These fractions were characterized by ion exchange with the chelating collector cellulose Hyphan by applying batch procedure. The metals were determined by atomic absorption spectrometry. The results show that the distribution coefficients, Kd, decreased with HS presence, and that the relative lability of metal fractions complexed by HS is dependent on variables such as pH, complexation time, and HS concentration. Until c.a. 15 min, the metal change between aquatic HS and ion exchanger occurs following a 2 order reaction. Afterwards, the remaining metal fraction in the HS reacts following a 1st order reaction. For traces of metal ions bound to dissolved HS, the lability orderPb > Mn > Cd, Ni > Cu is revealed. ©1997 Soc. Bras. Química.

Lability of Proteinaceous Material in Estuarine Seston and Subcellular Fractions of Phytoplankton

The rate of proteolysis of amino acids was used to assess the nutritional lability of various materials making up estuarine seston in 3 Maine, USA, estuaries. Physical separations of subcellular fractions of phytoplankton cells led to higher proteolysis rate constants for the cytoplasmic fraction (>1.2 h(-1)) than for the membrane fraction (0.2 to 1 h(-1)). Whole cells, copepod fecal pellets, bottom sediments, and estuarine seston had overlapping ranges of rate constants of 0.17 to 1.3 h(-1), which were indistinguishable from one another. Protein pools in the seston of these estuaries throughout the seasons were dominated by phytoplankton production and its fresh detrital products. Inverse relationships between proteolysis rate constants for estuarine seston and the ratios of pheopigments to chlorophyll indicates that the average lability of seston decreases with the disappearance of cytoplasmic material in suspension. This kinetic approach to the quality of food resources implies the existence of different pools of digestible protein for estuarine heterotrophs with different gut residence times. Preferential enrichment of membrane components in sestonic detritus may result from the differential lability of proteins in cytoplasm versus membrane components of cells.

Chromophore-bearing NH2-terminal domains of phytochromes A and B determine their photosensory specificity and differential light lability.

In early seedling development, far-red-light-induced deetiolation is mediated primarily by phytochrome A (phyA), whereas red-light-induced deetiolation is mediated primarily by phytochrome B (phyB). To map the molecular determinants responsible for this photosensory specificity, we tested the activities of two reciprocal phyA/phyB chimeras in diagnostic light regimes using overexpression in transgenic Arabidopsis. Although previous data have shown that the NH2-terminal halves of phyA and phyB each separately lack normal activity, fusion of the NH2-terminal half of phyA to the COOH-terminal half of phyB (phyAB) and the reciprocal fusion (phyBA) resulted in biologically active phytochromes. The behavior of these two chimeras in red and far-red light indicates: (i) that the NH2-terminal halves of phyA and phyB determine their respective photosensory specificities; (ii) that the COOH-terminal halves of the two photoreceptors are necessary for regulatory activity but are reciprocally inter-changeable and thus carry functionally equivalent determinants; and (iii) that the NH2-terminal halves of phyA and phyB carry determinants that direct the differential light lability of the two molecules. The present findings suggest that the contrasting photosensory information gathered by phyA and phyB through their NH2-terminal halves may be transduced to downstream signaling components through a common biochemical mechanism involving the regulatory activity of the COOH-terminal domains of the photoreceptors.

Stabilization of catalyst particles against sintering on oxide supports with high oxygen ion lability exemplified by Ir-catalyzed decomposition of N2O

Iridium nanoparticles deposited on a variety of surfaces exhibited thermal sintering characteristics that were very strongly correlated with the lability of lattice oxygen in the supporting oxide materials. Specifically, the higher the lability of oxygen ions in the support, the greater the resistance of the nanoparticles to sintering in an oxidative environment. Thus with γ-Al2O3 as the support, rapid and extensive sintering occurred. In striking contrast, when supported on gadolinia-ceria and alumina-ceria-zirconia composite, the Ir nanoparticles underwent negligible sintering. In keeping with this trend, the behavior found with yttria-stabilized zirconia was an intermediate between the two extremes. This resistance, or lack of resistance, to sintering is considered in terms of oxygen spillover from support to nanoparticles and discussed with respect to the alternative mechanisms of Ostwald ripening versus nanoparticle diffusion. Activity towards the decomposition of N2O, a reaction that displays pronounced sensitivity to catalyst particle size (large particles more active than small particles), was used to confirm that catalytic behavior was consistent with the independently measured sintering characteristics. It was found that the nanoparticle active phase was Ir oxide, which is metallic, possibly present as a capping layer. Moreover, observed turnover frequencies indicated that catalyst-support interactions were important in the cases of the sinter-resistant systems, an effect that may itself be linked to the phenomena that gave rise to materials with a strong resistance to nanoparticle sintering.

Sensitivity of organic matter decomposition to warming varies with its quality

The relationship between organic matter (OM) lability and temperature sensitivity is disputed, with recent observations suggesting that responses of relatively more resistant OM to increased temperature could be greater than, equivalent to, or less than responses of relatively more labile OM. This lack of clear understanding limits the ability to forecast carbon (C) cycle responses to temperature changes. Here, we derive a novel approach (denoted Q(10-q)) that accounts for changes in OM quality during decomposition and use it to analyze data from three independent sources. Results from new laboratory soil incubations (labile Q(10-q)=2.1 +/- 0.2; more resistant Q(10-q)=3.8 +/- 0.3) and reanalysis of data from other soil incubations reported in the literature (labile Q(10-q)=2.3; more resistant Q(10-q)=3.3) demonstrate that temperature sensitivity of soil OM decomposition increases with decreasing soil OM lability. Analysis of data from a cross-site, field litter bag decomposition study (labile Q(10-q)=3.3 +/- 0.2; resistant Q(10-q)=4.9 +/- 0.2) shows that litter OM follows the same pattern, with greater temperature sensitivity for more resistant litter OM. Furthermore, the initial response of cultivated soils, presumably containing less labile soil OM (Q(10-q)=2.4 +/- 0.3) was greater than that for undisturbed grassland soils (Q(10-q)=1.7 +/- 0.1). Soil C losses estimated using this approach will differ from previous estimates as a function of the magnitude of the temperature increase and the proportion of whole soil OM comprised of compounds sensitive to temperature over that temperature range. It is likely that increased temperature has already prompted release of significant amounts of C to the atmosphere as CO2. Our results indicate that future losses of litter and soil C may be even greater than previously supposed.

Direct evidence for base-mediated decomposition of alkyl hydroperoxides (ROOH) in the gas phase

Alkyl hydroperoxides (ROOH) are attributed a key role in the biochemical oxidation of lipids during oxidative stress.1 In this chemistry ROOH compounds, where the R groups are unsaturated fatty acids, are viewed as transient ntermediates which are readily degraded, due to the lability of the RO-OH bond, to yield potentially genotoxic aldehydes and ketones.2 Generally, the decomposition of alkyl hydroperoxides is thought to be mediated by radical abstraction or electron transfer processes usually involving enzymes, transition metals, or recently, Vitamin C.3 In this paper we present the first unambiguous experimental and computational evidence for base-mediated heterolytic decomposition of simple alkyl hydroperoxides by the mechanism outlined in Scheme 1.

Kohdennetut nanopartikkelit ja isotooppikuvantaminen syövän hoidossa

Syövän diagnostiikassa ja hoidossa nanopartikkelit voivat toimia kuljetinaineina lääke- ja diagnostisille aineille tai nukleiinihappojaksoille. Kantaja-aineeseen voidaan liittää kohdennusmolekyylejä partikkelien passiivista tai aktiivista kohdennusta varten tai radioleima kuvantamista tai radioterapiaa varten. Kantaja-aineiden avulla voidaan parantaa lääkeaineen fysikaalis-kemiallisia ominaisuuksia ja biologista hyötyosuutta, vähentää systeemisiä sivuvaikutuksia, pidentää lääkeaineen puoliintumisaikaa ja siten harventaa annosteluväliä, sekä parantaa lääkeaineen pääsyä kohdekudokseen. Näin voidaan parantaa kemo- ja radioterapian tehoa ja hoidon onnistumisen todennäköisyyttä. Kirjallisuuskatsauksessa perehdytään nanokantajien rooliin syövän hoidossa. Vuosikymmeniä jatkuneesta tutkimuksesta huolimatta vain kaksi (Eurooppa) tai kolme (Yhdysvallat) nanopartikkeliformulaatiota on hyväksytty markkinoille syövän hoidossa. Ongelmina ovat riittämätön hakeutuminen kohdekudokseen, immunogeenisyys ja nanopartikkelien labiilius. Kokeellisessa osassa tutkitaan in vitro ja hiirillä in vivo 99mTc-leimattujen, PEG-verhoiltujen biotiiniliposomien kaksivaiheista kohdennusta ihmisen munasarjan adenokarsinoomasoluihin. Kohdentamiseen käytetään biotinyloitua setuksimabi-(Erbitux®) vasta-ainetta, joka sitoutuu solujen yli-ilmentämiin EGF-reseptoreihin. Kaksivaiheista kohdennusta verrataan suoraan ja/tai passiiviseen kohdennukseen. Tehokkaampien kuvantamismenetelmien kehitys on vauhdittanut kohdennettujen nanopartikkelien tutkimusta. Isotooppikuvantamista käyttäen pystytään seuraamaan radioleiman jakautumista elimistössä ja kuvantamaan solutasolla tapahtuvia ilmiöitä. Kirjallisuuskatsauksessa perehdytään SPECT- ja PET-kuvantamiseen syövän hoidossa, sekä niiden hyödyntämiseen lääkekehityksessä nanopartikkelien kuvantamisessa. Kyseiset kuvantamismenetelmät erottuvat muista menetelmistä korkean erotuskyvyn, herkkyyden ja helppokäyttöisyyden suhteen. Kokeellisessa osassa 99mTc-leimattujen liposomien distribuutiota hiirissä tutkittiin SPECT-CT-laitteen avulla. Aktiivisuus kasvaimessa, pernassa ja maksassa kvantifioitiin InVivoScope-ohjelman ja gammalaskijan avulla. Tuloksia verrattiin keskenään. In vitro-kokeessa saavutettiin kaksivaiheisella kohdennuksella 2,7- 3,5-kertainen (solulinjasta riippuen) hakeutuminen soluihin kontrolliliposomeihin verrattuna. Kuitenkin suora kohdennus toimi kaksivaiheista kohdennusta paremmin in vitro. In vivo –kokeissa liposomit jakautuivat kasvaimeen tehokkaammin i.p.-annosteltuna kuin i.v.-annosteltuna. Kaksivaiheisella kohdennuksella saavutettiin 1,24-kertainen jakautuminen kasvaimeen (% ID/g kudosta) passiivisesti kohdennettuihin liposomeihin verrattuna. %ID/elin oli kohdennetuilla liposomeilla 5,9 % ja passiivisesti kohdennetuilla 5,4%. Todellinen ero oli siis pieni. InVivoScope:n ja gammalaskijan tulokset eivät korreloineet keskenään. Lisätutkimuksia ja menetelmän optimointia vaaditaan liposomien kohdennuksessa kasvaimeen.

Thermal degradation products of poly(styrenesulfides) investigated by direct pyrolysis�mass spectrometry and flash pyrolysis�gas chromatography/mass spectrometry

The thermal degradation products of two sulfur polymers, poly(styrenedisulfide) (PSD) and poly(styrenetetrasulfide) (PST), were investigated in parallel by direct pyrolysis-mass spectrometry (DPMS) and by flash pyrolysis-GC/MS (Py-GC/MS). The time-scale of the two pyrolysis techniques is quite different, and therefore they were able to detect significantly different products in the pyrolysis of PSD and PST because of the thermal lability of sulfur-containing compounds. However, the results obtained are not contradictory, and satisfactory mechanisms for the thermal degradation of PSD and PST have been derived from the overall evidence available. Pyrolysis compounds containing sulfur, styrene, and a number of cyclic styrene sulfides and diphenyldithianes have been observed by DPMS. However, in flash pyrolysis-GC/MS, styrene, sulfur, only one cyclic styrene sulfide, and two isomers of diphenylthiophene have been detected. These thiophene derivatives were indeed absent among the compounds obtained by DPMS because they were the terminal (most thermally stable) species arising from further decomposition of the cyclic styrene sulfides formed in the primary thermal degradation processes of PSD and PST.