No indications of persistent oxidative stress in response to an ironman triathlon

Introduction: Training for and competing in ultraendurance exercise events is associated with an improvement in endogenous antioxidant defenses as well as increased oxidative stress. However, consequences on health are currently unclear. Purpose: We aimed to examine the impact of training- and acute exercise-induced changes in the antioxidant capacity on the oxidant/antioxidant balance after an ironman triathlon and whether there are indications for sustained oxidative damage. Methods: Blood samples were taken from 42 well-trained male triathletes 2 d before an ironman triathlon, then immediately postrace, 1, 5, and 19 d later. Blood was analyzed for conjugated dienes (CD), malondialdehyde (MDA), oxidized low-density lipoprotein (oxLDL), oxLDL:LDL ratio, advanced oxidation protein products (AOPP), AOPP:total protein (TP) ratio, Trolox equivalent antioxidant capacity (TEAC), uric acid (UA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in erythrocytes. Results: Immediately postrace, there were significant increases in CD, AOPP, TEAC, UA (for all P < 0.001), and AOPP:TP (P < 0.01). MDA rose significantly (P < 0.01) 1 d postrace, whereas CD (P < 0.01), AOPP (P = 0.01), AOPP:TP (P < 0.05), and TEAC (P < 0.001) remained elevated. OxLDL:LDL trended to increase, whereas oxLDL significantly (P < 0.01) decreased 1 d postrace. Except for GSH-Px (P = 0.08), activities of SOD (P < 0.001) and CAT (P < 0.05) significantly decreased postrace. All oxidative stress markers had returned to prerace values 5 d postrace. Furthermore, several relationships between training status and oxidative stress markers, TEAC, and antioxidant enzyme activities were noted. Conclusions: This study indicates that despite a temporary increase in most (but not all) oxidative stress markers, there is no persistent oxidative stress in response to an ironman triathlon, probably due to training- and exercise-induced protective alterations in the antioxidant defense system.

Ozone-induced dissociation of conjugated lipids reveals significant reaction rate enhancements and characteristic odd-electron product ions

Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for \[M + X](+) ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.

One-step macroscopic alignment of conjugated polymer systems by epitaxial crystallization during spin-coating

The one-step preparation of highly anisotropic polymer semiconductor thin films directly from solution is demonstrated. The conjugated polymer poly(3-hexylthiophene) (P3HT) as well as P3HT:fullerene bulk-heterojunction blends can be spin-coated from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene (TCB) and a second carrier solvent such as chlorobenzene. Solidification is initiated by growth of macroscopic TCB spherulites followed by epitaxial crystallization of P3HT on TCB crystals. Subsequent sublimation of TCB leaves behind a replica of the original TCB spherulites. Thus, highly ordered thin films are obtained, which feature square-centimeter-sized domains that are composed of one spherulite-like structure each. A combination of optical microscopy and polarized photoluminescence spectroscopy reveals radial alignment of the polymer backbone in case of P3HT, whereas P3HT:fullerene blends display a tangential orientation with respect to the center of spherulite-like structures. Moreover, grazing-incidence wide-angle X-ray scattering reveals an increased relative degree of crystallinity and predominantly flat-on conformation of P3HT crystallites in the blend. The use of other processing methods such as dip-coating is also feasible and offers uniaxial orientation of the macromolecule. Finally, the applicability of this method to a variety of other semi-crystalline conjugated polymer systems is established. Those include other poly(3-alkylthiophene)s, two polyfluorenes, the low band-gap polymer PCPDTBT, a diketopyrrolopyrrole (DPP) small molecule as well as a number of polymer:fullerene and polymer:polymer blends. Macroscopic spherulite-like structures of the conjugated polymer poly(3-hexylthiophene) (P3HT) grow directly during spin-coating. This is achieved by processing P3HT or P3HT:fullerene bulk heterojunction blends from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene and a second carrier solvent such as chlorobenzene. Epitaxial growth of the polymer on solidified solvent crystals gives rise to circular-symmetric, spherulite-like structures that feature a high degree of anisotropy.

Electron-accepting conjugated materials based on 2-Vinyl-4,5- dicyanoimidazoles for application in organic electronics

We report the Heck coupling of 2-vinyl-4,5-dicyanoimidazole (vinazene) with selected di- and trihalo aromatics in an effort to prepare linear and branched electron-accepting conjugated materials for application in organic electronics. By selecting the suitable halo-aromatic moiety, it is possible to tune the HOMO - LUMO energy levels, absorption, and emission properties for a specific application. In this regard, materials with strong photoluminescence from blue → green → red are reported that may have potential application in organic light-emitting diodes (OLEDs). Furthermore, derivatives with strong absorption in the visible spectrum, coupled with favorable HOMO-LUMO levels, have been used to prepare promising organic photovoltaic devices (OPVs) when combined with commercially available semiconducting donor polymers.

A furan-containing conjugated polymer for high mobility ambipolar organic thin film transistors

Furan substituted diketopyrrolopyrrole (DBF) combined with benzothiadiazole based polymer semiconductor PDPP-FBF has been synthesized and evaluated as an ambipolar semiconductor in organic thin-film transistors. Hole and electron mobilities as high as 0.20 cm 2 V -1 s -1 and 0.56 cm 2 V -1 s -1, respectively, are achieved for PDPP-FBF.

Solid-state assemblies and optical properties of conjugated oligomers combining fluorene and thiophene units

Two conjugated oligomers, representing elementary segments of fluorene-thiophene copolymers, are compared in terms of the microscopic morphology and the optical properties of thin deposits. The atomic force microscopy morphological data and the solid-state absorption and emission spectra are interpreted in terms of the assembly of the conjugated molecules. The compound with a terthiophene central unit and fluorene end-groups shows well-defined monolayer-by-monolayer assembly into micrometer-long stripe-like structures, with a crystalline herringbone-type organization within the monolayers. Polarized confocal microscopy indicates a strong orientation of the crystalline domains within the stripes. In contrast, the compound with a terfluorene central unit and thiophene end groups forms no textured aggregates and the optical spectra in the solid-state are very similar to those recorded in solution, suggesting that the molecules interact only weakly in the solid. The difference in behaviour between the two compounds most probably originates from their different capability to form densely-packed assemblies of interacting π-systems.

Supramolecular organization in fluorene/indenofluorene-oligothiophene alternating conjugated copolymers

A series of conjugated copolymers containing fluorene or indenofluorene units alternating with oligothiophene segments, with potential interest for use as the active layer in field-effect transistors, is investigated. Atomic force microscopy analysis of the morphology of thin deposits shows either the formation of fibrillar structures, which are the signature of long-range π stacking, or the presence of untextured aggregates, resulting from disordered assembly. These morphologies are interpreted in terms of the supramolecular organization of the conjugated chains. Molecular modeling simulations indicate that the commensurability between the lengths of the monomer units and the presence of alkyl side groups are the two key structural factors governing the chain organization into highly ordered assemblies. The most favorable structures are those combining fluorene (indenofluorene) units with unsubstituted bithiophene (terthiophene) segments.

Pharmacokinetics and tumor disposition of PEGylated, methotrexate conjugated poly-l-lysine dendrimers

Dendrimers have potential for delivering chemotherapeutic drugs to solid tumours via the enhanced permeation and retention (EPR) effect. The impact of conjugation of hydrophobic anticancer drugs to hydrophilic PEGylated dendrimer surfaces, however, has not been fully investigated. The current study has therefore characterised the effect on dendrimer disposition of conjugating α-carboxyl protected methotrexate (MTX) to a series of PEGylated 3H-labelled poly-L-lysine dendrimers ranging in size from generation 3 (G3) to 5 (G5) in rats. Dendrimers contained 50% surface PEG and 50% surface MTX. Conjugation of MTX generally increased plasma clearance when compared to conjugation with PEG alone. Conversely, increasing generation reduced clearance, increased metabolic stability and reduced renal elimination of the administered radiolabel. For constructs with molecular weights >20 kDa increasing the molecular weight of conjugated PEG also reduced clearance and enhanced metabolic stability but had only a minimal effect on renal elimination. Tissue distribution studies revealed retention of MTX conjugated smaller (G3-G4) PEG570 dendrimers (or their metabolic products) in the kidneys. In contrast, the larger G5 dendrimer was concentrated more in the liver and spleen. The G5 PEG1100 dendrimer was also shown to accumulate in solid Walker 256 and HT1080 tumours and comparative disposition data in both rats (1 to 2% dose/g in tumour) and mice (11% dose/g in tumour) are presented. The results of this study further illustrate the potential utility of biodegradable PEGylated poly-L-lysine dendrimers as long circulating vectors for the delivery and tumour-targeting of hydrophobic drugs.

Pyrene based conjugated materials: synthesis, characterization and electroluminescent properties

In this work, three novel pyrene cored small conjugated molecules, namely 1,3,6,8-tetrakis(6-(octyloxy)naphthalene-2-yl)pyrene (PY-1), 1,3,6,8-tetrakis((E)-2-(6-(n-octyloxy)naphthalene-2-yl)vinyl)pyrene (PY-2) and 1,3,6,8-tetrakis((6-(n-octyloxy)naphthalene-2-yl)ethynyl)pyrene (PY-3) have been synthesized by Suzuki, heck and Sonogashira organometallic coupling reactions, respectively. The effects of single, double and triple bonds on their optical, electrochemical, and thermal properties are studied in detail. These are all materials fluorescent and they have been used in organic light-emitting diodes (OLEDs) and their electroluminescent properties have been studied.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Decision support system for contractor pre-qualification : artificial neural network model

The selection criteria for contractor pre-qualification are characterized by the co-existence of both quantitative and qualitative data. The qualitative data is non-linear, uncertain and imprecise. An ideal decision support system for contractor pre-qualification should have the ability of handling both quantitative and qualitative data, and of mapping the complicated nonlinear relationship of the selection criteria, such that rational and consistent decisions can be made. In this research paper, an artificial neural network model was developed to assist public clients identifying suitable contractors for tendering. The pre-qualification criteria (variables) were identified for the model. One hundred and twelve real pre-qualification cases were collected from civil engineering projects in Hong Kong, and eighty-eight hypothetical pre-qualification cases were also generated according to the “If-then” rules used by professionals in the pre-qualification process. The results of the analysis totally comply with current practice (public developers in Hong Kong). Each pre-qualification case consisted of input ratings for candidate contractors’ attributes and their corresponding pre-qualification decisions. The training of the neural network model was accomplished by using the developed program, in which a conjugate gradient descent algorithm was incorporated for improving the learning performance of the network. Cross-validation was applied to estimate the generalization errors based on the “re-sampling” of training pairs. The case studies show that the artificial neural network model is suitable for mapping the complicated nonlinear relationship between contractors’ attributes and their corresponding pre-qualification (disqualification) decisions. The artificial neural network model can be concluded as an ideal alternative for performing the contractor pre-qualification task.

Azoporphyrin : the porphyrin analogue of azobenzene

Azobenzenes (1,2-diaryldiazenes) are very important organic pigments, and they have a unique place in the field of photoresponsive conjugated molecules due to their (usually) reversible E/Z photoisomerisation. The current intense interest in molecular analogues of mechanical components and information storage and processing elements has stimulated research into conjugated molecules whose shape and/or optical properties can be switched electro- or photochemically. Among the classes of conjugated pigments being explored in these contexts are the porphyrinoids, which offer advantages of intense light absorption, a variety of accessible oxidation states, and synthetic control of properties through peripheral or central substitution. Extension of porphyrinoid conjugation can be achieved by linking the peripheral carbons either by three direct bonds (as in the “porphyrin tapes” of Osuka et al.) or through potentially conjugating bridges such as alkenes or, even better, alkynes.

An introduction to biologics

An introduction to biologics 23.1 Introduction: Principles of biologics and their use as medicines 23.2 Protein biologics used as drugs 23.2.1 Proteins that function through enzymatic or regulatory activity. 23.2.1.1 Biologics as replacement of a deficient or abnormal protein. 23.2.1.2 Proteins that augment an existing biological process. 23.2.1.3 Proteins that provide a novel function or activity. 23.2.2. Proteins that function through specific targeting activity. 23.2.2.1. Monoclonal antibody nomenclature. 23.2.2.2. Naked monoclonal antibodies. 23.2.2.3. Conjugated monoclonal antibodies. 23.2.3. Recombinant protein vaccines.