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Biomedical subjects

Brendan J Kennedy

Publications and source records attributed to Brendan J Kennedy.

12 recordsLinked to original sources
PubMed2006

Spatial distribution of lead in human primary teeth as a biomarker of pre- and neonatal lead exposure.

Lead remains one of the most hazardous toxins in our environment. Because the toxic effects of lead are most prominent during early development, it is important to develop a suitable biomarker for lead exposure during the pre- and neonatal periods. In the present study, the spatial distribution of lead was measured in the enamel and dentine of ten human primary teeth using laser ablation-inductively coupled plasma-mass spectrometry. The neonatal line, visualized using confocal laser scanning microscopy, was used to demarcate the pre- and postnatal regions of the sample teeth. Lead levels in pre- and postnatally formed enamel and dentine were compared to blood-lead levels measured at birth and one year of age for four of these participants. Mean dentine-lead levels ranged from 0.17+/-0.02 to 5.60+/-1.79 microg/g, and mean enamel-lead levels ranged from 0.04+/-0.01 to 1.47+/-0.20 microg/g. The results of this preliminary study showed that the spatial distribution of lead in dentine reflected the blood-lead levels. The present study demonstrates a methodology where the spatial distribution of lead in the dentine of human primary teeth may be used to obtain temporal information of environmental lead exposure during the pre- and neonatal periods.

Adolescent↗
PubMed2006

Structures and phase transitions in the ordered double perovskites Ba2BiIIIBiVO6 and Ba2BiIIISbVO6.

High-resolution neutron powder diffraction has been used to investigate the structures and phase transitions in the double perovskites Ba(2)Bi(3+)Bi(5+)O(6) (dibarium dibismuth hexaoxide) and Ba(2)BiSbO(6) (dibarium bismuth antimony hexaoxide) in the temperature ranges 4.2-973 and 4.2-625 K, respectively. The charge-ordered bismuthate adopts four structures in the temperature range - monoclinic in P2(1)/n, monoclinic in I2/m, rhombohedral in R3, and finally cubic in Fm3m. The low-temperature monoclinic structure has been determined for the first time. The transitions from P2(1)/n to I2/m, at 132 K, and R3 to Fm3m, at 820 K, are tricritical in nature; the transition from I2/m to R3 at ca 430 K is discontinuous. The behaviour of Ba(2)BiSbO(6) is very similar, except that the transition temperatures are lower - 250 K for I2/m to R3 and 515 K for R3 to Fm3m - and the low-temperature structure is not formed at all. The R3 to Fm3m transition in this compound is closer to second order in nature, although there is evidence for some contribution from higher-order terms.

Journal Article↗
PubMed2005

Structures of the ordered double perovskites Sr2YTaO6 and Sr2YNbO6.

The ordered perovskite Sr(2)YTaO(6), distrontium yttrium tantalum hexaoxide, has been reported as showing an unusual triclinic structure, at odds with the results from a recent group-theoretical analysis. A new investigation establishes that Sr(2)YTaO(6) and the isostructural Sr(2)YNbO(6), distrontium yttrium niobium hexaoxide, in fact both adopt the commonly occurring monoclinic structure, with the space-group symmetry P2(1)/n.

Calcium Compounds↗
PubMed2005

Nuclear magnetic resonance analysis of indomethacin-induced gastric ulcers.

Acetonitrile extracts of ulcerated and control rat stomachs were studied by various NMR techniques in an attempt to understand how indomethacin, a common and powerful nonsteroidal antiinflammatory drug (NSAID), induces ulcers in the stomach. One- (1D) and two-dimensional (2D) NMR spectra of extracts of ulcerated and control stomachs revealed that glycolytic and Krebs cycle enzymes were partially inhibited in the ulcerated stomach as shown by the lactate/glucose ratio. The (total choline)/lactate ratio was also higher in the extract from the control stomach than in the ulcerated stomach. Glycerophosphoethanolamine and glycerophosphocholine concentrations were higher in the ulcerated stomach extract as compared with the control stomach extract. These results explain the gastrointestinal protective effect of D-glucose and Krebs cycle intermediates on NSAID-induced ulceration.

Animals↗
PubMed2005

Spatial distribution of lead in enamel and coronal dentine of wistar rats.

Lead is one of the most hazardous environmental toxins known. The assessment of lead in dental hard tissues is important in the understanding of its toxic effects on oral tissues and in estimating exposure and body burden in individuals exposed to lead from the environment. However, current information on the uptake and distribution of lead in enamel and dentine is limited. The aim of this project was to study, at high resolution, the spatial distribution of lead in enamel and coronal dentine using an experimental rat model. A dose of 40 mg/L of lead nitrate was administered to pregnant female rats during the periods of gestation and lactation through drinking water. First mandibular molar teeth were removed from their 15-d-old pups and the distribution of lead was studied using a nuclear microprobe (NMP). The distribution of lead in enamel and coronal dentine showed four distinct zones with significantly different mean lead concentrations (p<0.05). High levels of lead were observed in the superficial regions of enamel and in the dentine directly adjacent to the pulp. Additionally, the results confirmed that the NMP is capable of mapping the distribution of lead in teeth at micron resolutions with a detection limit of approx 1 microg/g.

Animals↗
PubMed2004

NMR spectroscopic characterization of copper(II) and zinc(II) complexes of indomethacin.

Molecular diffusion constants were studied by NMR spectroscopy to provide information about the solution structures of a variety of Cu(II) and Zn(II) monomeric and dimeric complexes of indomethacin (IndoH). These studies showed that monomeric Zn(II)-Indo complexes substantially dimerize in DMF-d7 and DMSO-d6 solutions at room temperature, whereas the Cu(II) and Zn(II) dinuclear complexes remain largely intact in these solutions. There is evidence of an equilibrium between monomers and dimers for the Zn(II) complexes in solution, as shown by a reduced diffusion constant and lower average radius compared to the Cu(II) dimer. Such an equilibrium between monomers and dimers for the Zn(II) complexes is also consistent with previous results obtained from XAFS analysis of DMF solutions of such complexes. The greater lability and lower thermodynamic stability of the Zn(II) dimer complex compared to the Cu(II) analogue, as determined from the NMR experiments, is likely to result in the more ready release of free Indo in the GI tract. This is consistent with the previously observed higher GI toxicities of the Zn-Indo pharmaceutical preparations compared to the Cu(II)-Indo counterparts.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Spatial distribution of lead in the roots of human primary teeth.

Lead remains one of the most hazardous metals in our environment. The concentrations of lead in coronal dentine and enamel have previously been reported but limited information is available regarding lead levels in radicular dentine and cementum. This study reports the distribution of lead in 26 roots of 16 human maxillary primary teeth from seven individuals. In addition, calcium and phosphorous concentrations were also measured to detect any variations in the degree of mineralization in different regions of the roots. The mean lead concentration in these roots was 1.67 +/- 1.43 microg/g, which is comparable to other studies. In all cases there were higher lead concentrations in the apices of non-resorbed roots of primary maxillary teeth relative to middle and cervical regions. The findings reported here are of potential significance during the process of physiological root resorption whence periapical tissue may be exposed to higher levels of lead.

Calcium↗
PubMed2003

XAFS studies of anti-inflammatory dinuclear and mononuclear Zn(II) complexes of indomethacin.

Zinc K-edge X-ray absorption fine structure (XAFS) experiments were performed in the solid and solution states at low temperature (10 K), on dimeric and monomeric anti-inflammatory Zn(II) complexes of indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid=IndoH] of the formula [Zn2(Indo)4L2] [L=pyridine (Py), N,N-dimethylacetamide (DMA)], [Zn(Indo)2L2] [L=ethanol (EtOH), methanol (MeOH)], and Zn(II) acetate dihydrate [Zn(OAc)2(OH2)2]. The bond distances and angles obtained from multiple-scattering fits to the XAFS data of the Zn(II) dimeric complexes in the solid and solution states exhibit excellent correspondence with those obtained from single crystal diffraction studies. The Zn...Zn separations of 2.97 and 2.96 A and carboxylate group O-C-O angles of 125 degrees for powdered [Zn2(Indo)4(Py)2] and [Zn2(Indo)4(DMA)2] agree well with the XRD values of 2.969(1) and 2.9686(6) A and 125.8(4) degrees and 126.1(2) degrees, respectively. The calculated Zn-O(RCOO) and Zn-L bond distances of 2.03 and 2.04 A, or 2.02 and 1.98 A for Py or DMA complexes, respectively, also agree well with crystallographic data. The X-ray powder diffraction data on samples of the monomers exhibited additional reflections apart from those due to the crystallographically characterized cis-[Zn(eta2-O,O'-Indo)2L2], but microanalyses were consistent with this formulation. Therefore, mixed models that contained the cis complex and a second component consisting of a trans-six-coordinate complex, a five-coordinate complex, or a four-coordinate complex were used to model the XAFS. The best fits to the XAFS data were obtained with a mixture of the cis-six-coordinate complex and a four-coordinate complex containing two monodentate Indo ligands. The bond lengths for the six-coordinate structure were consistent with those determined on a single crystal, and those for the four-coordinate complexes were consistent with related four-coordinate structures with two monodentate carboxylate ligands. Dissolution of the dimer (DMA adduct) in DMF resulted in a mixture of dimer and monomer species as shown by MS XAFS fitting. This is the first time that solution structures have been determined for anti-inflammatory Zn(II) complexes, and this is an important first step in understanding the pharmacology of the complexes.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Ordered double perovskites -- a group-theoretical analysis.

Group-theoretical methods are used to enumerate the structures of ordered double perovskites, A(2)BB'X(6), in which the ordering of cations B and B' into alternate octahedra is considered in combination with the ubiquitous BX(6) (or B'X(6)) octahedral tilting. The cation ordering on the B-cation site is described by the irreducible representation R(1)(+) of the Pm3;m space group of the cubic aristotype, while the octahedral tilting is mediated by irreducible representations M(3)(+) and R(4)(+). There are 12 different structures identified, and the corresponding group-subgroup relationships are displayed. Known structures are briefly reviewed.

Journal Article↗
PubMed2003

Gastrointestinal toxicity, antiinflammatory activity, and superoxide dismutase activity of copper and zinc complexes of the antiinflammatory drug indomethacin.

Gastrointestinal (GI) toxicity is one of the major problems associated with antiinflammatory drugs. The complexation of the powerful antiinflammatory drug (IndoH) by metal ions, as a means of reducing GI toxicity, has been studied. The in vitro superoxide dismutase (SOD) activity, in vivo antiinflammatory activity, and gastrointestinal ulcerogenic properties of IndoH, [Cu2(Indo)4(DMF)2], and [Zn2(Indo)4(DMA)2] are reported. No SOD activity was observed for IndoH or [Zn2(Indo)4(DMA)2], but [Cu2(Indo)4(DMF)2] inhibited the reduction of nitroblue tetrazolium (NBT) at an IC50 value of 0.23 microM. All three compounds exhibited antiinflammatory activity in male Sprague-Dawley rats at an equivalent Indo dose of 10 mg/kg following oral administration of the drugs in 2% CMC solution. The severity of the toxicity (macroscopic ulcerations) in the stomach following oral dosing with [Zn2(Indo)4(DMF)2] was not significantly lower than that induced by IndoH (P = 0.78). Gastric ulcerations induced by [Cu2(Indo)4(DMF)2] were significantly lower than those induced by IndoH or [Zn2(Indo)4(DMA)2] (P = 0.0012 and P = 0.0175, respectively) but significantly greater than the control (P = 0.0013). The intestinal ulcerations induced by [Cu2(Indo)4(DMF)2] or [Zn2(Indo)4(DMA)2] were approximately 15 times lower than those of IndoH. A further indicator of gastrointestinal toxicity, caecal haemoglobin, increased in the following order: control < [Cu2(Indo)4(DMF)2] < [Zn2(Indo)4(DMA)2] < IndoH.[Cu2(Indo)4(DMF)2] exhibited the most promising results of the Indo complexes assayed, in that it exhibited SOD activity and the lowest gastrointestinal damage while also exhibiting antiinflammatory activity that was comparable to that for IndoH. Low-temperature EPR analyses also showed that the formulation used for [Cu2(Indo)4(DMF)2] administration was crucial to the integrity of the complex.

Animals↗
PubMed2002

Hard X-ray microprobe studies of chromium(VI)-treated V79 Chinese hamster lung cells: intracellular mapping of the biotransformation products of a chromium carcinogen.

The uptake of carcinogenic and mutagenic Cr compounds and the intracellular distribution of their biotransformation products in V79 Chinese hamster lung cells were studied by synchrotron-radiation-induced X-ray emission (SRIXE). SRIXE analysis was performed on whole cells that had been treated with either Cr(III) or Cr(V) 1,10-phenanthroline complexes, or Cr(VI). The high spatial resolution (0.3 microm) and elemental sensitivity (~10(-15) g Cr/cell) of the technique provided detailed maps of Cr and other cellular elements in thin sections prepared from Cr(VI)-treated cells. The Cr carcinogen concentrated in P-rich regions corresponding to the nucleus, as well as other areas of the cell that are likely to correspond to organelles. This is the first study that has enabled the determination of the localization of the biotransformation products of Cr(VI) carcinogens in a target lung cell.

Animals↗