Chris Silwood

BSc(Hons), PhD

Research skills

  • Technical
    • Physical/clinical chemist with substantial experience in the application of spectroscopic, chemometric and data fitting methods to complex chemical and biochemical problems, • This experience includes the analysis of biomarkers and metabolites in a range of biological matrices, e.g. saliva, Synovial Fluid, including those samples resulting from clinical trials, • Parallel skills have also been developed in the characterisation of oxidised culinary and essential oils, • A list of published research papers, book chapters, patents and conference presentations is available at http://www.chrissilwood.talktalk.net
  • IT
    extensive experience of Microsoft Office (Word, Powerpoint, Excel, ACD/Labs SpecManager/Predictor platforms, Biorad spectroscopic software
  • Statistical
    extensive experience of Statistica, chemometric statistical packages, e.g. Excel add-ins
  • Other
    • Is enthusiastic, Flexible, conscientious, and well organised, • Is able to work as part of a team as well as being able to supervise and mentor others coming from a wide range of multicultural/multiethnic backgrounds, • Has worked in a variety of laboratory, Hospital, academic and industrial environments, both in the UK and overseas

Research interests

  • Interests
    Chemometrics, Drug Development, Medical Devices, Consultant, Essential Oils, Pharmacokinetics, vegetable oils, physical/clinical chemistry, food health/safety, biofluid assays, salivary research, general troubleshooting, liaising with academic and industrial contacts, NMR Spectroscopy, Lipid, High Performance Liquid Chromatography (HPLC)

Research experience

  • Feb 2010
    Research: Viral-induced salivary NMR biomarker detection
    University of Bolton · Institute for Materials Research and Innovation · University of Bolton
    Bolton
    • The employment of multivariate chemometric techniques for viral-induced salivary NMR biomarker detection in a series of patients, including comparisons of the salivary NMR profiles with those of non-medically-compromised, healthy human volunteers. Both supervised pattern recognition and non-supervised exploratory data analyses have been utilised, an emphasis being placed on the use of novel in-house variable selection methods for analysis optimisation and examination of the sources of variation (disease classification, sampling day and participant)
  • Aug 2008–
    Apr 2009
    Research: Caze Filters Ltd
    London
    • Advised on restaurant trials concerned with the on-site testing of a novel filtration device for maintaining the shelf life of culinary oils and reducing the development of toxic oxidation products and trans fats
  • Aug 2008–
    Feb 2009
    Research: Botanic Oil Innovations Inc.
    Spooner, Wisconsin
    • Characterised a range of essential oils extracted from fruit and vegetable seeds, identifying a variety of phytochemical components that possess potential antioxidant, anti-inflammatory, antibacterial and anticancer properties
  • Sep 2004–
    Jul 2008
    Research: LSBU
    London South Bank University · Applied Science · London South Bank University
    Martin Grootveld · London
    • Identified the precise chemical forms of potentially toxic metals released from hip- and knee- joint prosthetic replacements in biological media, focussing on cobalt(II), chromium(III), titanium(IV), aluminium(III) and vanadium(III), (IV) and (V) • Presented the findings from >5 years of studies at a due diligence meeting convened in Paris, France, concerned with one particular metallodrug candidate, developed in London, that had successfully completed pre-clinical evaluation, liaising with executives representing French and American companies • Liaised with a University spin-in food company, playing a major role in monthly progress meetings and being fully involved in the agreement of milestone timelines towards the ultimate aim of introduction to the marketplace of their product • Advised coffee companies on appropriate chemical remedies for detrimental processes occurring within their commercial products • Established a collaboration with the Chemometrics Unit, University of Bristol, concerned with the development of novel variable selection methods for the analysis of salivary sample NMR datasets
  • Jul 2000–
    Aug 2004
    Research: DMM
    St. Bartholomews and the Royal London School of Medicine and Dentistry · Department of Diabetes and Metabolic Medicine · St. Bartholomews and the Royal London School of Medicine and Dentistry
    Graham Hitman · London
    • Constructed experimental biofluid 1H NMR spectral databases (saliva, urine, blood cells and plasma, synovial, seminal and cerebrospinal fluids) for incorporation into the ACD/Labs NMR Manager software platform • Oversaw the synthetic design and pre-clinical testing of fluoro-titanium(IV)-containing antimicrobial/antioxidant/anticariogenic pharmaceutical candidates and related hydroxyapatite bioceramic materials, including pharmacokinetic and dissolution studies (1H/19F NMR and UV-VIS spectroscopies, HPLC, specific ion electrode), where appropriate, for a variety of substrate ligands • Developed LC-NMR/LC-MS assays for the indexing of pancreatic -cell components in both control and dysfunctional cells with diabetic phenotypes, the studies highlighting a variety of nucleoside/ nucleotide moieties • Advised one particular dental company on the application of chemometric methods, leading to a model for the diurnal variation of salivary metabolic markers for oral disease activity
  • Oct 1995–
    Jun 2000
    Research: BJRU
    St. Bartholomews and the Royal London School of Medicine and Dentistry · Bone and Joint Research Unit · St. Bartholomews and the Royal London School of Medicine and Dentistry
    David Blake · London
    • Applied novel NMR spectroscopic and chemometric statistical techniques (e.g. PCA, PLS, PLS-DA) to the analysis of chemical markers in biofluids and tissue samples (“normal” and inflammatory) • Studied the pathogenesis of disease processes in vivo (such as atherosclerosis) initiated by the presence of LOPs generated within culinary oils following their thermal stressing • Was a member of a two centre (London, Madrid) team that linked the presence of LOPs within thermally stressed culinary oils with teratogenic actions in rats • Designed NMR/HPLC assays for the detection of potentially deleterious breakdown products leached from dental resin materials • Separated and identified tree bark constituents purported to possess anti-inflammatory and/or anti-HIV properties (HPLC, 1H NMR spectroscopy, mass spectrometry, in conjunction with Prof John Oxford) • Employed multinuclear (1H,13C,31P,19F) NMR/UV-VIS/FT-IR spectroscopic techniques for the characterisation of dental product components contained within saliva and plaque • Developed NMR spectral assays for the simultaneous detection of sorbitol, xylitol and mannitol in a variety of chewing gum materials • Determined the effect of various oral healthcare products on the alleviation of oral malodour associated with the production of volatile sulphur compounds (VSCs)

Education

  • Oct 1984–
    Sep 1987
    Birkbeck College, University of London
    Chemistry · PhD
    United Kingdom · London
  • Oct 1981–
    Jul 1984
    University of Leeds
    Chemistry · BSc(Hons)
    United Kingdom · Leeds

Other

  • Languages
    a working knowledge of French

Publications

  • 1.41
    Impact points
    High-resolution (1)H NMR investigations of the oxidative consumption of salivary biomolecules by oral rinse peroxides.

    Hubert Chang, Christopher J L Silwood, Edward Lynch, Martin Grootveld

    Acta odontologica Scandinavica. 04/2012;

    Abstract Background. A multicomponent evaluation of the oxidative consumption of salivary biomolecules by a tooth-whitening oral rinse preparation has been performed using high-resolution proton ((1)H) nuclear magnetic resonance spectroscopy (NMR). Methods. Unstimulated human saliva samples (n = 12)... [more] Abstract Background. A multicomponent evaluation of the oxidative consumption of salivary biomolecules by a tooth-whitening oral rinse preparation has been performed using high-resolution proton ((1)H) nuclear magnetic resonance spectroscopy (NMR). Methods. Unstimulated human saliva samples (n = 12) were treated with aliquots of the oral rinse tested and 600 MHz (1)H NMR spectra acquired on these samples demonstrated that hydrogen peroxide (H(2)O(2)) and/or peroxodisulphate (S(2)O(8) (2-)) present in this product gave rise to the oxidative decarboxylation of the salivary electron-donor pyruvate (to acetate and CO(2)), and also oxidized methionine (a precursor to volatile sulphur compounds responsible for oral malodour), and malodourous trimethylamine to methionine sulphoxide and trimethylamine-N-oxide, respectively (reductions observed in the salivary concentrations of each biomolecular peroxide-scavenging agent were all extremely statistically significant, p < 0.005). Results. Experiments conducted on chemical model systems confirmed the consumption of pyruvate by this product, and also revealed that the amino acids cysteine and methionine were oxidatively transformed to cystine and methionine sulphoxide, respectively. Conclusions. High-field (1)H NMR analysis provides much valuable molecular information regarding the fate of tooth-whitening oxidants in human saliva and permits an assessment of the mechanisms of action of oral healthcare products containing these agents. The biochemical and potential therapeutic significance of the results obtained are discussed.
  • 3.05
    Impact points
    (1)H NMR investigations of the molecular nature of cobalt(II) ions in human saliva.

    Hubert Chang, Shigetaka Tomoda, Christopher J L Silwood, Edward Lynch, Martin Grootveld

    Archives of biochemistry and biophysics. 02/2012; 520(1):51-65.

    High-resolution (1)H NMR spectroscopy demonstrated that addition of Co(II) ions to isolated human salivary supernatants (HSSs) gave rise to its complexation by a variety of biomolecules. The relative efficacies of these complexants/chelators in this context were classifiable by the influence of adde... [more] High-resolution (1)H NMR spectroscopy demonstrated that addition of Co(II) ions to isolated human salivary supernatants (HSSs) gave rise to its complexation by a variety of biomolecules. The relative efficacies of these complexants/chelators in this context were classifiable by the influence of added Co(II) on their line-widths and chemical shift values, and also the added Co(II) concentration-dependence of these spectral modifications. Those which were most affected by the addition of this metal ion were lactate > formate ≈histidinate > succinate, this order reflecting the ability of these complexants to compete for the available Co(II) in terms of (1) thermodynamic equilibrium constants for the formation of their complexes and (2) their HSS concentrations. Since many of these HSS Co(II) complexants (particularly lactate, formate and histidine) serve as powerful ()OH scavengers, the results acquired indicate that any of this radical generated from the Co(II) source in such complexes via pseudo-Fenton reactions may be 'site-specifically' scavenged. The significance of these observations regarding the in vivo corrosion of cobalt-containing metal alloy dental prostheses (e.g., Co-Cr alloys), the availability of trace levels of this metal ion in human saliva, and cobalt toxicity, is discussed.
  • 5.21
    Impact points
    Supervised self organizing maps for classification and determination of potentially discriminatory variables: illustrated by application to nuclear magnetic resonance metabolomic profiling.

    Kanet Wongravee, Gavin R Lloyd, Christopher J Silwood, Martin Grootveld, Richard G Brereton

    Analytical chemistry. 01/2010; 82(2):628-38.

    The article describes the extension of the self organizing maps discrimination index (SOMDI) for cases where there are more than two classes and more than one factor that may influence the group of samples by using supervised SOMs to determine which variables and how many are responsible for the dif... [more] The article describes the extension of the self organizing maps discrimination index (SOMDI) for cases where there are more than two classes and more than one factor that may influence the group of samples by using supervised SOMs to determine which variables and how many are responsible for the different types of separation. The methods are illustrated by an application in the area of metabolic profiling, consisting of a nuclear magnetic resonance (NMR) data set of 96 samples of human saliva, which is characterized by three factors, namely, whether the sample has been treated or not, 16 donors, and 3 sampling days, differing for each donor. The sampling days can be considered a null factor as they should have no significant influence on the metabolic profile. Methods for supervised SOMs involve including a classifier for organizing the map, and we report a method for optimizing this by using an additional weight that determines the relative importance of the classifier relative to the overall experimental data set in order to avoid overfitting. Supervised SOMs can be obtained for each of the three factors, and we develop a multiclass SOM discrimination index (SOMDI) to determine which variables (or regions of the NMR spectra) are considered significant for each of the three potential factors. By dividing the data iteratively into training and test sets 100 times, we define variables as significant for a given factor if they have a positive SOMDI in the training set for the factor and class of interest over all iterations.
  • Self Organising Maps for variable selection: Application to human saliva analysed by nuclear magnetic resonance spectroscopy to investigate the effect of an oral healthcare product

    Gavin R. Lloyd, Kanet Wongravee, Christopher J.L. Silwood, Martin Grootveld, Richard G. Brereton

    Chemometrics and Intelligent Laboratory Systems. 10/2009; 98:149-161.

    SOMs (Self Organising Maps) are derived from the machine learning literature and serve as a valuable method for representing data. In this paper, the use of SOMs as a technique for determining the most significant variables (or markers) in a dataset is described. The method is applied to the NMR spe... [more] SOMs (Self Organising Maps) are derived from the machine learning literature and serve as a valuable method for representing data. In this paper, the use of SOMs as a technique for determining the most significant variables (or markers) in a dataset is described. The method is applied to the NMR spectra of 96 human saliva samples, half of which have been treated with an oral rinse formulation and half of which are controls, and 49 variables consisting of bucketed intensities. In addition, three simulations, two of which consist of the same number of samples and variables as the experimental dataset and a third that contains a much larger number of variables, are described. Two of the simulations contain known discriminatory variables, and the remaining is treated as a null dataset without any specific discriminatory variables added. The described SOM method is contrasted to Partial Least Squares Discriminant Analysis, and a list of the markers determined to be most significant using both approaches was obtained and the differences arising are discussed. A SOM Discrimination Index (SOMDI) is defined, whose magnitude relates to how strongly a variable is considered to be a discriminator. In order to ensure that the model is stable and not dependent on the random starting point of the SOM, one hundred iterations were performed and variables that were consistently of high rank were selected. A variety of approaches for data representation are illustrated, and the main theoretical principles of employing SOMs for determining which variables are most significant are outlined. Software used in this paper was written in-house, allowing greater flexibility over existing packages, and tailored for the specific application in hand.
  • 2.55
    Impact points
    High extracellular glucose inhibits exocytosis through disruption of syntaxin 1A-containing lipid rafts.

    Sangeeta Somanath, Sebastian Barg, Catriona Marshall, Christopher J Silwood, Mark D Turner

    Biochemical and biophysical research communications. 09/2009;

    Diabetes is characterized by high blood glucose which eventually impairs the secretion of insulin. Glucose directly affects cholesterol biosynthesis and may in turn affect cellular structures that depend on the sterol, including lipid rafts that help organize the secretory apparatus. Here, we invest... [more] Diabetes is characterized by high blood glucose which eventually impairs the secretion of insulin. Glucose directly affects cholesterol biosynthesis and may in turn affect cellular structures that depend on the sterol, including lipid rafts that help organize the secretory apparatus. Here, we investigated the long-term effects of glucose upon lipid rafts and secretory granule dynamics in pancreatic beta-cells. Raft fractions, identified by the presence of GM1 and flotillin, contained characteristically high levels of cholesterol and syntaxin 1A, the t-SNARE which tethers granules to the plasma membrane. Seventy-two hours exposure to 28mM glucose resulted in approximately 30% reduction in membrane cholesterol, with consequent redistribution of raft markers and syntaxin 1A throughout the plasma membrane. Live cell imaging indicated loss of syntaxin 1A from granule docking sites, and fewer docked granules. In conclusion, glucose-mediated inhibition of cholesterol biosynthesis perturbs lipid raft stability, resulting in a loss of syntaxin 1A from granule docking sites and inhibition of insulin secretion.
  • 2.19
    Impact points
    High-resolution (1)H NMR investigations of the capacity of dentifrices containing a "smart" bioactive glass to influence the metabolic profile of and deliver calcium ions to human saliva.

    Martin Grootveld, Christopher J L Silwood, Walter T Winter

    Journal of biomedical materials research. Part B, Applied biomaterials. 05/2009;

    Dentifrices containing H(2)O-reactive bioactive glasses alleviate hypersensitivity in teeth via the blockage of open dentinal tubules. Here, the ability of two such products to release Ca(2+) ions into human saliva was investigated, together with their influence on the status of this biofluid's ... [more] Dentifrices containing H(2)O-reactive bioactive glasses alleviate hypersensitivity in teeth via the blockage of open dentinal tubules. Here, the ability of two such products to release Ca(2+) ions into human saliva was investigated, together with their influence on the status of this biofluid's (1)H NMR-detectable biomolecules. Human salivary supernatants were equilibrated with increasing volumes of those derived from each dentifrice (5.00 min at 37 degrees C). These biofluids were also equilibrated at 37 degrees C with a preselected quantity of the intact products (samples were collected at increasing timepoints). Salivary Ca(2+) concentrations were monitored by a (1)H NMR technique involving ethylenediamine tetra-acetate addition and/or atomic absorption spectrometry. Added Ca(2+)- and dentifrice supernatant volume (DSV)-induced modifications to the salivary (1)H NMR profile were explored by spectral titration. Data acquired demonstrated added DSV-dependent increases in salivary Ca(2+) concentrations and (Ca(2+)-independent) modifications to the intensities of selected salivary (1)H NMR signals, particularly those of the malodorous amines methyl-, dimethyl-, and trimethylamines, which were diminished by up to 80% of their prior values. Time-dependent elevations in salivary Ca(2+) level were observed on equilibration with the intact dentifrices. Added Ca(2+) ions exerted a concentration-dependent influence on a range of resonances (including those of citrate, succinate, pyruvate, and lactate). These data provide valuable information regarding the mechanisms of action of the products tested. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009.
  • 2.54
    Impact points
    1H and 51V NMR investigations of the molecular nature of implant-derived vanadium ions in osteoarthritic knee-joint synovial fluid.

    Christopher J L Silwood, Martin Grootveld

    Clinica chimica acta; international journal of clinical chemistry. 06/2007; 380(1-2):89-99.

    BACKGROUND: High field (1)H and (51)V NMR spectroscopies were employed to determine the oxidation state and complexation status of vanadium ions in intact osteoarthritic knee-joint synovial fluid (OA SF) when pre-added as V(III)((aq.)), V(IV)((aq.)) and V(V)((aq.)). METHODS: Aliquots of each vanadiu... [more] BACKGROUND: High field (1)H and (51)V NMR spectroscopies were employed to determine the oxidation state and complexation status of vanadium ions in intact osteoarthritic knee-joint synovial fluid (OA SF) when pre-added as V(III)((aq.)), V(IV)((aq.)) and V(V)((aq.)). METHODS: Aliquots of each vanadium solution were added to the SF samples and their (1)H NMR spectra recorded. (51)V NMR spectra were also recorded for the samples to which V(III)((aq.)) had been added. Theoretical computer simulations of the competitive complexation of vanadium ions by a range of low-molecular-mass biomolecules were also performed. RESULTS: The spectroscopic results demonstrated that addition of vanadium ions to intact OA SF gave rise to their complexation by a range of low-molecular-mass biomolecules. The results indicated the physiologically-significant complexing abilities of histidine, threonine, glycine, tyrosine and citrate for each of the added metal ions. The computer simulations revealed that the relative capacity of OA SF complexants to compete for available V(III), V(IV) and V(V) ions reflected the thermodynamic stability constants for such complexes and their available concentrations in this biofluid. CONCLUSIONS: Since comparatively low concentrations of added metal ion are required to selectively influence spectral properties, the "speciation" of prostheses-derived metal ions in biofluids and tissues can be ascertained through the facile employment of high resolution NMR spectroscopy.
  • 0.91
    Impact points
    High resolution 1H NMR investigations of the oxidative consumption of salivary biomolecules by ozone: relevance to the therapeutic applications of this agent in clinical dentistry.

    Martin Grootveld, Christopher J L Silwood, Edward Lynch

    BioFactors (Oxford, England). 02/2006; 27(1-4):5-18.

    High resolution proton (1H) nuclear magnetic resonance (NMR) spectroscopy was employed to simultaneously evaluate the oxidising actions of ozone (O3) towards a wide range of salivary biomolecules in view of its applications in dental practices, which may serve as a viable and convenient means for th... [more] High resolution proton (1H) nuclear magnetic resonance (NMR) spectroscopy was employed to simultaneously evaluate the oxidising actions of ozone (O3) towards a wide range of salivary biomolecules in view of its applications in dental practices, which may serve as a viable and convenient means for the treatment of dental caries. Treatment of supernatants derived from unstimulated human saliva specimens (n=12) with O3 (4.48 mmol) revealed that this reactive oxygen species gave rise to the oxidative consumption of pyruvate (generating acetate and CO2 as products), lactate (to pyruvate and sequentially acetate and CO2), carbohydrates in general (a process generating formate), methionine (giving rise to its corresponding sulphoxide), and urate (to allantoin). Further, minor O3-induced modifications included the oxidation of trimethylamine and 3-D-hydroxybutyrate, the fragmentation of salivary glycosaminoglycans to NMR-detectable saccharide fragments, and the conversion of polyunsaturated fatty acids to their ozonides. Moreover, evidence for the ability of O3 to induce the release of selected low-molecular-mass salivary biomolecules from macromolecular binding-sites was also obtained. Since many of the oxidation products detectable in O3-treated samples are identical to those arising from the attack of *OH radical on biofluid components, it appears that at least some of the modifications observed here are attributable to the latter oxidant (derived from O3*- generated from the single electron reduction of O3).
  • 0.91
    Impact points
    Determination of the illicit drug gamma-hydroxybutyrate (GHB) in human saliva and beverages by 1H NMR analysis.

    Martin Grootveld, Deborah Algeo, Christopher J L Silwood, John C Blackburn, Anthony D Clark

    BioFactors (Oxford, England). 02/2006; 27(1-4):121-36.

    High resolution 1H NMR spectroscopy has been employed to investigate the detection and quantification of the illicit "date-rape" drug gamma-hydroxybutyrate (GHB) in both human saliva and a commonly-consumed low-alcohol beer product. Data acquired revealed that this multicomponent analytica... [more] High resolution 1H NMR spectroscopy has been employed to investigate the detection and quantification of the illicit "date-rape" drug gamma-hydroxybutyrate (GHB) in both human saliva and a commonly-consumed low-alcohol beer product. Data acquired revealed that this multicomponent analytical technique provided unequivocal evidence for the detection of this agent by this technique in both of these matrices, i.e., all three of its resonances [those ascribable to the alpha-CH2 (t, delta=2.25 ppm), beta-CH2 (tt, delta=1.81 ppm) and gamma-CH2 (t, delta=3.61 ppm) group protons] were present in spectra acquired on human saliva, and two of these (the alpha- and beta-CH2 group signals) in the beverage product examined, the latter observation attributable to overlap of the gamma-CH2 1H resonance with those of carbohydrates. Since good linear calibration relationships between the intensities of each of the NMR-visible signals and added GHB concentration (the former normalised to that of an external 3-trimethylsilyl [2,2,3,3-2H4]- propionate standard present in a coaxial NMR tube insert) were observed, this illicit drug is also readily quantifiable in such multicomponent samples. Our data demonstrate the advantages offered by this technique when applied to the analysis of illicit drugs in multicomponent sample matrices such as human biofluids and beverage products.
  • 4.66
    Impact points
    Evaluation of the speciation status of aluminium(III) ions in isolated osteoarthritic knee-joint synovial fluid.

    Christopher J L Silwood, Martin Grootveld

    Biochimica et biophysica acta. 11/2005; 1725(3):327-39.

    High field 1H NMR spectroscopy demonstrated that the equilibration of added Al(III) ions in osteoarthritic (OA) knee-joint synovial fluid (SF) resulted in its complexation by citrate and, to a much lesser extent, tyrosine and histidine. The ability of these ligands, together with inorganic phosphate... [more] High field 1H NMR spectroscopy demonstrated that the equilibration of added Al(III) ions in osteoarthritic (OA) knee-joint synovial fluid (SF) resulted in its complexation by citrate and, to a much lesser extent, tyrosine and histidine. The ability of these ligands, together with inorganic phosphate, to compete for the available Al(III) in terms of (1) thermodynamic equilibrium constants for the formation of their complexes and (2) their SF concentrations was probed through the use of computer speciation calculations, which considered low-molecular-mass binary and ternary Al(III) species, the predominant Al(III) plasma transport protein transferrin, and also relevant hydrolysis and precipitation processes. It was found that, at relatively low added Al(III) concentrations, citrate species were more favoured, whilst phosphate species became dominant at higher levels. The significance of these findings with regard to the in vivo corrosion of aluminium-containing metal alloy joint prostheses (e.g., TiAlV alloys) is discussed.
  • 2.55
    Impact points
    Chemical nature of implant-derived titanium(IV) ions in synovial fluid.

    Christopher J L Silwood, Martin Grootveld

    Biochemical and biophysical research communications. 06/2005; 330(3):784-90.

    Previous investigations have indicated a deleterious leakage of Ti(III) and/or Ti(IV) species from Ti-Al-V alloy joint prostheses into adjacent tissue, synovium or synovial fluid (SF) in vivo. In view of the importance of the particular chemical nature of such complexes in determining their biologic... [more] Previous investigations have indicated a deleterious leakage of Ti(III) and/or Ti(IV) species from Ti-Al-V alloy joint prostheses into adjacent tissue, synovium or synovial fluid (SF) in vivo. In view of the importance of the particular chemical nature of such complexes in determining their biological activity, we have employed high field proton (1H) NMR spectroscopy to "speciate" Ti(IV) in inflammatory SF. Treatment of osteoarthritic SF samples with increasing concentrations of Ti(IV) (0.10-1.03 mM [TiO(C2O4)2]2-) gave rise to a specific broadening of the citrate proton resonances, indicating that this bioavailable oxygen-donor ligand plays an important role in complexing implant-derived Ti(IV). 1H NMR analysis of Ti(IV)-loaded SF samples subsequently treated with a large excess of ascorbate (0.05 M) showed that this added Ti(IV) chelator was only poorly effective in removing this metal ion from Ti(IV)-citrate/Ti(IV)-oxycitrate complexes. The results obtained here provide evidence for complexation of the low-molecular-mass (non-protein-bound) fraction of implant-derived Ti(IV) by citrate in vivo.
  • 3.25
    Impact points
    Examination of the molecular nature of low-molecular-mass chromium(III) ions in isolated osteoarthritic knee-joint synovial fluid.

    Christopher J L Silwood, Martin Grootveld

    Journal of inorganic biochemistry. 06/2005; 99(6):1390-400.

    High field (1)H NMR spectroscopy demonstrated that equilibration of added Cr(III) ions in osteoarthritic knee-joint synovial fluid (SF) resulted in its complexation by a range of biomolecules, the relative efficacies of these complexants/chelators being threonine approximately alanine>glycine>... [more] High field (1)H NMR spectroscopy demonstrated that equilibration of added Cr(III) ions in osteoarthritic knee-joint synovial fluid (SF) resulted in its complexation by a range of biomolecules, the relative efficacies of these complexants/chelators being threonine approximately alanine>glycine>glutamine>citrate>histidine approximately phenylalanine approximately tyrosine>valine approximately isoleucine approximately leucine>glutamate>lactate approximately acetate approximately formate approximately pyruvate, this order reflecting the ability of these ligands to compete for the available Cr(III) in terms of (1) thermodynamic equilibrium constants for the formation of their complexes and (2) their SF concentrations. The significance of these observations with regard to the in vivo corrosion of chromium-containing metal alloy joint prostheses (e.g., CoCr alloys) is discussed.
  • 2.55
    Impact points
    1H NMR analysis as a diagnostic probe for human saliva.

    Martin Grootveld, Christopher J L Silwood

    Biochemical and biophysical research communications. 05/2005; 329(1):1-5.

    The applications of high resolution (1)H NMR analysis as a diagnostic probe for human saliva are reviewed with special reference to diabetes mellitus, and a recently published report regarding the ability of this technique to detect advanced glycation endproducts (AGEs) in this biofluid [Biochem. Bi... [more] The applications of high resolution (1)H NMR analysis as a diagnostic probe for human saliva are reviewed with special reference to diabetes mellitus, and a recently published report regarding the ability of this technique to detect advanced glycation endproducts (AGEs) in this biofluid [Biochem. Biophys. Res. Commun. 323 (2004) 377-381]. We also demonstrate that hypochlorous acid/hypochlorite (HOCl/OCl(-))-induced modifications to the (1)H NMR profiles of human salivary supernatants arise from the chlorination and, where appropriate, oxidation of amino acids and malodorous amines, together with the oxidation of carbohydrates and alpha-keto acid anions. The attack of HOCl/OCl(-) on carbohydrates yields formate (singlet, delta = 8.46 ppm), the (1)H NMR signal of which was erroneously assigned to AGE species by the authors of [Biochem. Biophys. Res. Commun. 323 (2004) 377-381].
  • 2.22
    Impact points
    Investigation of the molecular nature of low-molecular-mass cobalt(II) ions in isolated osteoarthritic knee-joint synovial fluid.

    Christopher J L Silwood, Ian C Chikanza, K Elizabeth Tanner, Julia C Shelton, John G Bowsher, Martin Grootveld

    Free radical research. 06/2004; 38(6):561-71.

    High field 1H NMR spectroscopy demonstrated that addition of Co(II) ions to osteoarthritic knee-joint synovial fluid (SF) resulted in its complexation by a range of biomolecules, the relative efficacies of these complexants/chelators being citrate >> histidine - threonine >> glycine - gl... [more] High field 1H NMR spectroscopy demonstrated that addition of Co(II) ions to osteoarthritic knee-joint synovial fluid (SF) resulted in its complexation by a range of biomolecules, the relative efficacies of these complexants/chelators being citrate >> histidine - threonine >> glycine - glutamate - glutamine - phenylalanine tyrosine > formate > lactate >> alanine > valine > acetate > pyruvate > creatinine, this order reflecting the ability of these ligands to compete for the available Co(II) in terms of (1) thermodynamic equilibrium constants for the formation of their complexes and (2) their SF concentrations. Since many of these SF Co(II) complexants (e.g. histidinate) serve as powerful *OH scavengers, the results acquired indicate that any of this radical generated from the Co(II) source in such complexes via Fenton or pseudo-Fenton reaction systems will be "site-specifically" scavenged. The significance of these observations with regard to cobalt toxicity and the in vivo corrosion of cobalt-containing metal alloy joint prostheses (e.g. CoCr alloys) is discussed.
  • 4.92
    Impact points
    Multicomponent analysis of encapsulated marine oil supplements using high-resolution 1H and 13C NMR techniques.

    Navaede Siddiqui, Julia Sim, Christopher J L Silwood, Harold Toms, Richard A Iles, Martin Grootveld

    Journal of lipid research. 01/2004; 44(12):2406-27.

    Multicomponent high-resolution 1H and 13C NMR analysis has been employed for the purpose of detecting and quantifying a wide range of fatty acids (as triacylglycerols or otherwise) in encapsulated marine cod liver oil supplements. The 1H NMR technique provided quantitative data regarding the docosah... [more] Multicomponent high-resolution 1H and 13C NMR analysis has been employed for the purpose of detecting and quantifying a wide range of fatty acids (as triacylglycerols or otherwise) in encapsulated marine cod liver oil supplements. The 1H NMR technique provided quantitative data regarding the docosahexaenoic acid content of these products, which serves as a valuable index of fish oil quality, and a combination of both 1H and 13C spectroscopies permitted the analysis of many further components therein, including sn-1 monoacylglycerols, sn-1,2 and -1,3 diacylglycerol adducts, together with a range of minor components, such as trans-fatty acids, free glycerol and cholesterol, and added vitamins A and E. The identities of each of the above agents were confirmed by the application of two-dimensional 1H-1H spectroscopies. The NMR techniques employed also uniquely permitted determinations of the content of nonacylglycerol forms of highly unsaturated (or other) fatty acids in these products (i.e., ethyl esters), and therefore served as a means of distinguishing "natural" sources of cod liver oils from those subjected to chemical modification to and/or supplementation with synthetic derivatives such as ethyl docosahexaenoate or eicosopentaenoate. The analytical significance and putative health effects of the results acquired are discussed.
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Following (5)

45
Publications
31
Followers
Past advisors
Prof Martin Grootveld Prof Edward Lynch Prof Ray Matthews Prof David B Davies