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Biomedical subjects

M Grootveld

Publications and source records attributed to M Grootveld.

At least 19 recordsLinked to original sources
PubMed2001

EDTA bis-(ethyl phenylalaninate): a novel transition metal-ion chelating hydroxyl radical scavenger with a potential anti-inflammatory role.

Conjugation of ethylenediaminetetraacetic acid (EDTA) to ethyl phenylalaninate generates a novel radical scavenging metal-ion chelator EDTA bis-(ethyl phenylalaninate) (EBEP). The oxidation products o-, m- and p-tyrosine were isolated from hydrolysed, aqueous and aerated solutions containing EBEP, Fe(II) and H(2)O(2). Data obtained demonstrate the potential of EBEP to act as a radical scavenging, iron-ion chelating antioxidant under physiologically relevant conditions.

Anti-Inflammatory Agents↗
PubMed2001

Evidence for the microbicidal activity of a chlorine dioxide-containing oral rinse formulation in vivo.

The ability of an oral rinse preparation, containing an admixture of the oxohalogen oxidants chlorite anion and chlorine dioxide, to diminish salivary levels of Streptococcus mutans, lactobacilli and Candida albicans was investigated in a group of 33 dental patients. Patients underwent oral rinsing episodes with the above product (20 ml for a period of 60 seconds, three times daily) for a total of 14 days, and subsequently repeated this exercise with mineral water in place of the oral rinse formulation. A group of 10 dental student volunteers, conducting the same oral rinsing regimens with mineral water in place of the oral health care product, served as a control group. Salivary microorganism levels were determined both prior and subsequent to the above trial period. The results demonstrated that biocidal oxohalogen oxidants present in the oral rinse formulation tested gave rise to a substantial reduction in salivary S. mutans and lactobacilli levels (p < 0.001 and 0.005, respectively), although the decrease observed in C. albicans failed to reach statistical significance. As expected, mineral water employed as an oral rinsing system by the same group of patients, or the student control group, exerted no influence on the salivary levels of each of these microorganisms. The therapeutic, microbial and biochemical ramifications of the results obtained are discussed.

Adult↗
PubMed1999

Examination of the metabolic status of rat air pouch inflammatory exudate by high field proton NMR spectroscopy.

High field proton (1H) NMR spectroscopy was employed to investigate the metabolic status of rat air pouch inflammatory exudates obtained subsequent to the induction of inflammation with carrageenan, and the 1H NMR profiles of these fluids were compared and contrasted with those of inflammatory human synovial fluid, rat plasma and human serum. The characteristic biochemical features obtained from 1H NMR analysis of these exudates consisted of (1) substantially elevated levels of lactate (11.40+/-1.46x10-3 mol dm-3 for samples collected at a time point of 24 h post induction) with little or no NMR-detectable glucose, data consistent with a hypoxic environment and consequent anaerobic metabolism in the inflamed air pouch, and (2) high levels of the ketone body 3-d-hydroxybutyrate, providing evidence for an increased utilization of fats for energy by lymphocytes, the predominant leucocytes present in this environment. These phenomena represent a pathological extreme of the abnormal metabolic status of inflammatory human synovial fluids.

Air↗
PubMed1999

Application of high-resolution, two-dimensional 1H and 13C nuclear magnetic resonance techniques to the characterization of lipid oxidation products in autoxidized linoleoyl/linolenoylglycerols.

Subjection of polyunsaturated fatty acid (PUFA)-rich culinary oils to standard frying episodes generates a range of lipid oxidation products (LOP), including saturated and alpha,beta-unsaturated aldehydes which arise from the thermally induced fragmentation of conjugated hydroperoxydiene precursors. Since such LOP are damaging to human health, we have employed high-resolution, two-dimensional 1H-1H relayed coherence transfer, 1H-1H total correlation, 1H-13C heteronuclear multiple quantum correlation, and 1H-1H J-resolved nuclear magnetic resonance (NMR) spectroscopic techniques to further elucidate the molecular structures of these components present in (i) a model linoleoylglycerol compound (1,3-dilinolein) allowed to autoxidize at ambient temperature and (ii) PUFA-rich culinary oils subjected to repeated frying episodes. The above techniques readily facilitate the resolution of selected vinylic and aldehydic resonances of LOP which appear as complex overlapping patterns in conventional one-dimensional spectra, particularly when employed in combination with solvent-induced spectral shift modifications. Hence, much useful multi-component information regarding the identity and/or classification of glycerol-bound conjugated hydroperoxydiene and hydroxydiene adducts, and saturated and alpha,beta-unsaturated aldehydes, present in autoxidized PUFA matrices is provided by these NMR methods. Such molecular information is of much value to researchers investigating the deleterious health effects of LOP available in the diet.

Carbon Isotopes↗
PubMed1999

The role of N-acetylcysteine in protecting synovial fluid biomolecules against radiolytically-mediated oxidative damage: a high field proton NMR study.

High field proton (1H) NMR spectroscopy has been employed to evaluate the abilities of the antioxidant thiol drug N-acetylcysteine and exogenous cysteine to protect metabolites present in intact inflammatory synovial fluid samples against oxidative damage arising from gamma-radiolysis (5.00 kGy) in the presence of atmospheric O2. Although oxidation of urate to allantoin by radiolytically-generated *OH radical was readily circumventable by pre-treatment of synovial fluids with N-acetylcysteine (1.00 or 3.00 x 10(-3) mol x dm(-3)) or cysteine (1.00, 2.00 or 5.00 x 10(-3) mol x dm(-3)), both thiols offered only a limited protective capacity with respect to hyaluronate depolymerisation and the production of formate from carbohydrates in general. Radiolytic products generated from the added thiols (predominantly their corresponding disulphides) were simultaneously detectable in 1H Hahn spin-echo spectra of gamma-irradiated synovial fluids, permitting a quantitative evaluation of the radioprotective capacity of these agents. It is concluded that the multicomponent analytical ability of high field 1H NMR spectroscopy provides much useful molecular information regarding mechanisms associated with the radioprotectant actions of thiols in intact biofluids.

Acetylcysteine↗
PubMed1998

In vivo absorption, metabolism, and urinary excretion of alpha,beta-unsaturated aldehydes in experimental animals. Relevance to the development of cardiovascular diseases by the dietary ingestion of thermally stressed polyunsaturate-rich culinary oils.

Thermal stressing of polyunsaturated fatty acid (PUFA)- rich culinary oils according to routine frying or cooking practices generates high levels of cytotoxic aldehydic products (predominantly trans-2-alkenals, trans,trans-alka-2,4-dienals, cis,trans-alka-2, 4-dienals, and n-alkanals), species arising from the fragmentation of conjugated hydroperoxydiene precursors. In this investigation we demonstrate that typical trans-2-alkenal compounds known to be produced from the thermally induced autoxidation of PUFAs are readily absorbed from the gut into the systemic circulation in vivo, metabolized (primarily via the addition of glutathione across their electrophilic carbon-carbon double bonds), and excreted in the urine as C-3 mercapturate conjugates in rats. Since such aldehydic products are damaging to human health, the results obtained from our investigations indicate that the dietary ingestion of thermally, autoxidatively stressed PUFA-rich culinary oils promotes the induction, development, and progression of cardiovascular diseases.

Aldehydes↗
PubMed1997

Multicomponent investigations of the hydrogen peroxide- and hydroxyl radical-scavenging antioxidant capacities of biofluids: the roles of endogenous pyruvate and lactate. Relevance to inflammatory joint diseases.

High field proton (1H) nuclear magnetic resonance (NMR) analysis of biofluids (health human blood sera and inflammatory knee-joint synovial fluids) has been employed to evaluate the hydrogen peroxide (H2O2)- and hydroxyl radical (0OH)- scavenging antioxidant capacities of a range of polar, low-molecular-mass endogenous metabolites therein. Data obtained indicate that consumption of H2O2 by pyruvate (generating acetate and CO2 via an oxidative decarboxylation reaction) and 0OH radical by lactate (generating pyruvate, and subsequently acetate and CO2) may serve to protect alternative biofluid components (e.g., macromolecules) against reactive oxygen species-mediated oxidative damage in vivo. The mechanistic, physiological and potential therapeutic implications of these results are discussed with special reference to inflammatory joint diseases.

Adult↗
PubMed1997

Multicomponent spectroscopic investigations of salivary antioxidant consumption by an oral rinse preparation containing the stable free radical species chlorine dioxide (ClO2.).

A multicomponent evaluation of the oxidative consumption of salivary biomolecules by a commercially-available oral rinse preparation containing an admixture of the stable free radical species chlorine dioxide (ClO2.) with chlorite anion (ClO2-) has been investigated using high resolution 1H NMR spectroscopy. The results obtained demonstrated that ClO2. and/or ClO2- present in this preparation effected the oxidative decarboxylation of salivary pyruvate (to acetate and CO2). Experiments conducted on chemical model systems confirmed the oxidative decarboxylation of pyruvate by this oral rinse, and also demonstrated that urate, thiocyanate anion, and the amino acids cysteine and methionine (precursors to volatile sulphur compounds responsible for oral malodour), were oxidatively consumed. The biochemical, periodontal and therapeutic significance of the results are discussed.

Absorption↗
PubMed1995

Detection and investigation of the molecular nature of low-molecular-mass copper ions in isolated rheumatoid knee-joint synovial fluid.

Low-molecular-mass copper(II) species have been detected and quantified in ultrafiltrates (n = 7) of rheumatoid synovial fluid (SF) by a highly-sensitive HPLC-based assay system with the ability to determine Cu(II) concentrations of < 10(-7) mol.dm-3. High field 1H NMR spectroscopy demonstrated that addition of Cu(II)(aq.) to isolated samples of RA SF ultrafiltrates resulted in complexation by histidine > alanine > formate > threonine > lactate > tyrosine > phenylalanine, their effectiveness in this context being in the given order. CD spectra of Cu(II)-treated samples of intact SF exhibited absorption bands typical of copper(II)-albumin complexes, in addition to a band attributable to a low-molecular-mass histidinate complex (lambda min 610 nm). Since both albumin and histidine are potent radical scavengers, these results indicate that any .OH radical generated from bound copper ions will be 'site-specifically' scavenged. Hence, low-molecular-mass copper complexes with the ability to promote the generation of .OH radical which can then escape from the metal ion co-ordination sphere (and in turn, cause damage to critical biomolecules) appear to be absent from inflammatory SF.

Adult↗
PubMed1993

A comparative evaluation of the metabolic profiles of normal and inflammatory knee-joint synovial fluids by high resolution proton NMR spectroscopy.

High resolution 1H NMR spectroscopy has been employed to investigate the metabolic profile of healthy human knee-joint synovial fluid (SF) and the biochemical data acquired have been compared with those of matched serum, and inflammatory knee-joint SF samples. Results obtained indicate that the healthy human knee-joint has a hypoxic status (high lactate level when expressed relative to that of paired serum) that is milder than that of the inflamed human knee-joint. Moreover, normal SF differs from that of inflammatory SF in that it contains little or no NMR-detectable lipoprotein-associated fatty acids and 'acute-phase' glycoproteins, an observation reflecting the limited passage of these macromolecules from plasma into the synovial space in healthy subjects.

Acute-Phase Proteins↗
PubMed1993

Generation of substance P carbamate in neutral aqueous solution. Relevance to inflammatory joint diseases.

High-field proton (1H) nuclear magnetic resonance (NMR) spectroscopy has been employed to evaluate the formation of substance P carbamate in aqueous solution. Equilibration of substance P with physiologically relevant concentrations of bicarbonate (2.50 x 10(-2) mol.dm-3) at pH 7.00 generated a new multiplet signal centred at 4.13 ppm in its NMR spectrum, characteristic of the alpha-proton of peptide carbamate species. High-field 1H NMR spectroscopy also demonstrated that the model dipeptide, Arg-Gly, formed a carbamate in neutral aqueous solutions containing 2.50 x 10(-2) mol.dm-3 HCO3-. The physiological significance of these results is discussed in view of the central roles of vasoactive neuropeptides in human joint diseases and the hypercapnic environment of the inflamed rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1993

High resolution proton NMR investigations of rat blood plasma. Assignment of resonances for the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins.

An intense broad resonance at 2.14 ppm present in high field (400, 500 and 600 MHz) Hahn spin-echo 1H-NMR spectra of rat blood plasma, but absent from those of human blood plasma is attributable to the presence of terminal O-acetylsialate sugars in the molecularly mobile carbohydrate side-chains of 'acute-phase' glycoproteins (predominantly alpha 1-acid glycoprotein). The presence of such alternative acetylsugars in the carbohydrate side-chains of rat plasma glycoproteins are of much physiological and experimental significance in view of the regular use of these animals in model systems of human inflammatory conditions.

Acute-Phase Proteins↗
PubMed1993

An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy.

The 1H Hahn spin-echo NMR profiles of rheumatoid synovial fluids have been investigated and compared with those of matched serum samples. In addition to markedly elevated lactate and diminished glucose concentrations, inflammatory synovial fluids contained (i) substantially lower levels of NMR-detectable chylomicron-and very-low-density-lipoprotein-associated triacylglycerols which appear to have a shortened mean chain-length, and (ii) high concentrations of ketone bodies (predominantly 3-D-hydroxybutyrate), relative to those of corresponding paired serum samples. These observations confirm the abnormal metabolic status of the inflamed rheumatoid joint and provide evidence for an increased utilisation of lipids for fuel therein.

3-Hydroxybutyric Acid↗
PubMed1993

An optical hydroxyl radical sensor.

A hydroxyl radical (.OH) fibre-optic sensor has been developed. An .OH radical-sensitive reagent phase (nitrophenol) was immobilized onto XAD-7 methacrylate beads. Subsequently the beads were attached to the distal end of a polymethylmethacrylate fibre optic. Nitrocatechol, generated from the attack of .OH radical on nitrophenol, exhibits a strong absorption band in the visible region of the electromagnetic spectrum (lambda max = 510 nm). Here, reflectance spectroscopy was employed to monitor the concomitant intensity decrease in the reflectance spectrum upon .OH radical attack. The sensor exhibited excellent stability and linearity of response to .OH generated by a Fenton reaction system (EDTA, Fe(II) and H2O2) with H2O2 over the concentration range of 3.6 x 10(-6)-8.0 x 10(-2) M.

Fiber Optic Technology↗
PubMed1992

Alpha-tocopherol, lipids and lipoproteins in knee-joint synovial fluid and serum from patients with inflammatory joint disease.

1. We have determined the antioxidant status of synovial fluid and serum of patients with inflammatory joint disease in terms of the biologically active lipid-soluble antioxidant, alpha-tocopherol. Synovial fluid concentrations of alpha-tocopherol were significantly lower relative to those of paired serum samples (P < 0.001). Serum levels of alpha-tocopherol in these patients did not differ significantly from those in control serum. 2. Lower concentrations of cholesterol, triacylglycerol and low-density lipoprotein were also observed in patients' synovial fluid compared with matched serum samples. However, multiple regression analysis of the data indicated that there remained a significant depletion of alpha-tocopherol, which was largely independent of these co-variables, in inflammatory synovial fluid. These findings are consistent with the consumption of alpha-tocopherol within the inflamed joint via its role in terminating the process of lipid peroxidation. 3. Nuclear magnetic resonance spectroscopic analysis of matched inflammatory synovial fluid and serum confirmed lower concentrations of triacylglycerol in synovial fluid together with evidence of a shortened mean triacylglycerol chain length. The latter metabolic difference suggests an increased utilization of triacylglycerols for energy within the inflamed joint.

Arthritis↗
PubMed1991

Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy.

Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.

Adult↗