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Biomedical subjects

R Moseley

Publications and source records attributed to R Moseley.

At least 19 recordsLinked to original sources
PubMed2003

The influence of fluoride on the cellular morphology and synthetic activity of the rat dentine-pulp complex in vitro.

Exposure to high fluoride concentrations in the immediate environment of the tissue is recognized to result in the post-translational modification of non-collagenous dentine extracellular matrix (ECM) components, potentially altering dentine mineralization. However, less is known about the effects of fluoride exposure on the morphology or metabolism of the cells associated with the dentine-pulp complex. This study examined the effects of fluoride exposure at defined concentrations on the cellular morphology and ECM synthetic activities of odontoblasts and pulpal fibroblasts by the culture of tooth sections from male Wistar rat incisors in Trowel-type cultures for up to 14 days, in the presence and absence of 6mM sodium fluoride. Histomorphometric analysis of the dentine-pulp complex of sodium fluoride-exposed tooth sections demonstrated no obvious gross morphological differences with respect to the odontoblasts and pulpal fibroblasts throughout the 14-day culture period, in comparison with unexposed tooth sections. No significant differences in odontoblast and pulpal fibroblast cell numbers were determined in the absence and presence of fluoride. Image analysis examination of odontoblast cytoplasmic:nuclear (C/N) ratios also showed no significant differences in fluoride-exposed and unexposed tooth sections, although reductions in the C/N ratios of pulpal fibroblasts were evident in fluoride-exposed sections at days 10 and 14. No significant differences in predentine width were observed in fluoride-exposed and unexposed tooth sections over the 14-day culture period. Autoradiography following [3H]proline incorporation into the dentine-pulp complex demonstrated inhibition of collagen synthesis, particularly by the odontoblasts in tooth sections exposed to 6mM sodium fluoride. These findings, in association with those from previous studies, imply that dentine ECM alterations may contribute to the altered mineralization of dentine during fluorosis, rather than secretory-related changes in odontoblast morphology.

Animals↗
PubMed2003

Comparison of the antioxidant properties of wound dressing materials--carboxymethylcellulose, hyaluronan benzyl ester and hyaluronan, towards polymorphonuclear leukocyte-derived reactive oxygen species.

In chronic wounds, factors are released which perpetuate inflammatory processes, including polymorphonuclear leukocyte (PMN)-derived reactive oxygen species (ROS), such as superoxide radical (O(2)*-) and hydroxyl radical (*OH) species. The glycosaminoglycan, hyaluronan, has established antioxidant properties towards ROS, although the antioxidant potential of wound dressing biomaterials, such as 75% benzyl esterified hyaluronan (BEHA) and carboxymethylcellulose (CMCH), are less characterised. This study compared the antioxidant properties of high and low molecular weight hyaluronan (HMWT HA and LMWT HA), BEHA and CMCH towards ROS, generated by stimulated PMN in vitro. The antioxidant capacities of each biomaterial were assessed by their inhibition of O(2)*- -induced cytochrome C reduction, generated via PMN stimulation by phorbol myristyl acetate (PMA); and their inhibition of *OH-induced 2-deoxy-D-ribose degradation, generated by PMA stimulated PMN in the presence of a ferric chloride-EDTA chelate. All biomaterials, except LMWT HA, possessed dose-dependent antioxidant properties against O(2)*-, BEHA having greatest antioxidant potential, followed by HMWT HA and CMCH. HMWT HA exhibited the highest dose-dependent antioxidant properties towards *OH, followed by BEHA and CMCH. LMWT HA demonstrated no antioxidant properties towards *OH. These antioxidant activities, particularly towards O(2)*-, may be beneficial in removing the initial source of ROS necessary for the secondary formation of *OH, implicated as a causal factor for the extensive metabolic alterations observed in chronic wounds.

Antioxidants↗
PubMed2002

Comparison of the antioxidant properties of HYAFF-11p75, AQUACEL and hyaluronan towards reactive oxygen species in vitro.

In chronic wounds, a number of host factors are released which perpetuate the inflammatory process, including polymorphonuclear leukocyte (PMN)-derived reactive oxygen species (ROS), such as superoxide radical (O2*-) and hydroxyl radical (*OH) species. The glycosaminoglycan. hyaluronan, has been shown to act as an antioxidant towards ROS, although the potential for biomaterials, such as HYAFF -11p75 (the 75% benzyl ester of hyaluronan) and AQUACEL (carboxymethylcellulose), to act in this manner has yet to be elucidated. This study compared the antioxidant properties of high and low molecular weight hyaluronan (HMWT HA and LMWT HA), HYAFF -11p75, AQUACEL and an AQUACEL /hyaluronan composite (AQUACEL /HA) against O2*- and *OH. The antioxidant capacities of each material were assessed by their ability to inhibit cytochrome C reduction by O2*- fluxes, generated via the oxidation of hypoxanthine by xanthine oxidase, and their inhibition of 2-deoxy-D-ribose degradation by *OH fluxes, generated by the reaction of hydrogen peroxide (H2O2) and iron (Fe2+). All materials studied possessed dose dependent antioxidant properties towards O2*-, with HYAFF 11p75 having the greatest antioxidant potential towards these species, followed by AQUACEL, HMWT HA, AQUACEL /HA and LMWT HA. Only HMWT HA exhibited dose dependent antioxidant properties towards *OH at the fluxes examined. Gas chromatography/mass spectrometry analysis implied that ester bonds between the hyaluronan backbone and benzyl groups of HYAFF -11p75 are highly susceptible to O2*- hydrolysis, with the de-esterified benzyl alcohol being rapidly degraded in the presence of *OH. This data supports the hypothesis that HYAFF -11p75 has greater antioxidant capacity towards O2*-, due to the esterified benzyl groups providing alternative sites for O2*- attack other than the hyaluronan backbone of HYAFF -11p75 itself and explains the inability of HYAFF -11p75 to scavenge *OH, due to benzyl alcohol degradation by *OH. The antioxidant activities of these biomaterials, particularly HYAFF -11p75 and AQUACEL, towards O2*- could be beneficial, as the scavenging of PMN-derived O2*- may remove initial sources of O2*- and further prevent the secondary formation of *OH. These ROS are thought to be a primary causal factor for the extensive degradation and metabolic alterations observed in chronic wounds.

Antioxidants↗
PubMed2002

TGF-beta latency-associated peptides (LAPs) in human dentin matrix and pulp.

Transforming growth factor (TGF)-beta s in dentin matrix provide a pool of bioactive molecules, but association with latency-associated peptides (LAPs) may influence their activity. We investigated TGF-beta 1, -beta 2, and -beta 3 LAP expression in sound and carious human teeth. Teeth were fixed and processed immediately following extraction prior to staining with rabbit polyclonal antibodies to the TGF-beta LAPs. A soluble dentin matrix fraction was prepared from dissected human dentin and sequential extraction of pulpal ECM was performed prior to purification. Fractions were Western blotted and probed with the LAP antibodies. All three LAPs were present in odontoblasts, cells of the pulp, and predentin; however, no staining of mineralized dentin matrix was seen. Similar patterns of expression were seen in carious tissue. Expression of TGF-beta LAPs in cells and pulpal matrix of healthy and carious teeth will be important in regulation of TGF-beta activity and may modulate the tissue response to injury.

Dental Caries↗
PubMed2000

A randomized, controlled trial to assess a novel colorectal cancer screening strategy: the conversion strategy--a comparison of sequential sigmoidoscopy and colonoscopy with immediate conversion from sigmoidoscopy to colonoscopy in patients with an abnormal screening sigmoidoscopy.

OBJECTIVE: Our study was a randomized, controlled trial to assess a novel strategy that provides comprehensive colorectal cancer screening in a single visit versus traditional sigmoidoscopy and, where appropriate, colonoscopy on a subsequent day. METHODS: Consecutive patients referred for screening were randomized to control or so-called "conversion" groups. Patients in the control group were prepared for sigmoidoscopy with oral phospho-soda. Those with an abnormal sigmoidoscopy were scheduled for colonoscopy on a future day after oral polyethylene glycol preparation. In the conversion group, patients were prepared with oral phosphosoda. Patients with a polyp >5 mm or multiple diminutive polyps were converted from sigmoidoscopy to colonoscopy, allowing comprehensive screening in a single visit. Clinical outcomes were assessed by postprocedure physician and patient questionnaires. RESULTS: Two hundred thirty-five patients were randomized (control = 121, conversion = 114). In the control group, 28% had an indication for colonoscopy. Three of 33 (9%) with an abnormal sigmoidoscopy did not return for colonoscopy. At colonoscopy, 27% had a proximal adenoma. In the conversion group, 28% had an abnormal sigmoidoscopy and underwent conversion to colonoscopy. Forty-one percent undergoing colonoscopy in the conversion group had a proximal adenoma. Physicians reported no differences in preparation or procedure difficulty, whereas patients reported no differences in the level of comfort or overall satisfaction between groups. When queried regarding preferences for future screening, 96% chose the conversion strategy. CONCLUSIONS: The conversion strategy led to similar outcomes compared to traditional screening while improving compliance with colonoscopy in patients with an abnormal sigmoidoscopy.

Adenoma↗
PubMed2000

Reactive oxygen species: a potential role in the pathogenesis of periodontal diseases.

The pathological events leading to the destruction of the periodontium during inflammatory periodontal diseases are likely to represent complex interactions involving an imbalance in enzymic and non-enzymic degradative mechanisms. This paper aims to review the increasing body of evidence implicating reactive oxygen species (ROS), derived from many metabolic sources, in the pathogenesis of periodontal tissue destruction. ROS are generated predominantly by polymorphonuclear leukocytes (PMN) during an inflammatory response and are regarded as being highly destructive in nature. The detection of ROS oxidation products, the elevation of iron and copper ions, which catalyse the production of the most reactive radical species, and the identification of an imbalance in the oxidant/antioxidant activity within periodontal pockets, suggests a significant role for ROS in periodontal tissue destruction. In vitro studies have shown that ROS are capable of degrading a number of extracellular matrix components including proteoglycans, resulting in the modification of amino acid functional groups, leading to fragmentation of the core protein, whilst the constituent glycosaminoglycan chains undergo limited depolymerisation. The identification and characterisation of connective tissue metabolites in gingival crevicular fluid (GCF) resulting from the degradation of periodontal tissues, notably alveolar bone, provides further evidence for a role for ROS in tissue destruction associated with inflammatory periodontal diseases.

Antioxidants↗
PubMed1998

The modification of alveolar bone proteoglycans by reactive oxygen species in vitro.

Reactive oxygen species (ROS) are being increasingly implicated in the connective tissue degradation associated with chronic inflammatory conditions, such as periodontal disease. The present study investigated the effects of ROS on the proteoglycans (PG) of alveolar bone which are important structural components within the periodontium. PG were isolated from ovine alveolar bone and exposed to increasing concentrations of hydrogen peroxide (H2O2) or to a hydroxyl radical (.OH) flux for 1 h or 24 h, and the degradation products examined for depolymerisation and chemical modification of the PG structure. ROS were demonstrated to be capable of degrading alveolar bone PG in vitro, the .OH species resulting in greater modification than H2O2. The degradative effects observed included cleavage of the protein core and depolymerisation of the GAG chains. The core proteins were more susceptible to degradation than the GAG chains in the presence of H2O2 alone, although both the core proteins and the GAG chains were extensively degraded in the presence of a .OH flux for both 1 h and 24 h. Exposure of the PG to .OH for 24 h resulted in significant modification to the amino acid composition with decreases in the proportion of leucine and the complete loss of proline, tyrosine and phenylalanine evident. The results highlight the potential role of ROS as an important mechanism in considering the pathology of periodontal tissue destruction.

Alveolar Bone Loss↗
PubMed1997

Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes.

The effect of reactive oxygen species (ROS), generated by in vitro stimulation of isolated PMN upon the main GAG components of mineralised and non-mineralised connective tissues was investigated. PMN were isolated from whole blood and the production of the ROS superoxide (O2.-) and hydroxyl radicals (.OH) was stimulated by the addition of phorbol myristyl acetate (PMA) and PMA/FeCl3-EDTA chelate respectively and their production assessed over a 24 h period. The glycosaminoglycans (GAG), hyaluronan, chondroitin 4-sulphate and dermatan sulphate, were exposed to the ROS fluxes, incubated at 37 degrees C for 1 h and 24 h. GAG fragmentation was examined by gel exclusion chromatography and modification to hexuronic acid and hexosamine residues determined. Stimulation of PMN with PMA resulted in a burst of O2.- production for 1 h, which was sustained at a reduced level for 24 h. Fragmentation of GAG was observed for all GAG examined. Modification to the GAG was evident, with hyaluronan being more susceptible to loss of GAG residues than sulphated GAG. Modification of sugar residues increased with the incubation time and loss of the hexuronic acid residues was greater than loss of hexosamine residues. Addition of FeCl3-EDTA chelate, which led to the generation of .OH and was sustained over the 24 h period, demonstrated similar trends of GAG modification although increased degradation and loss of hexosamine and hexuronic acid were observed. GAG chains are constituents of PGs and their modification is likely to affect the function of these macromolecules and be of importance in considering the pathogenesis of inflammatory diseases, including periodontal diseases.

Glycosaminoglycans↗
PubMed1996

Influence of titanium oxide and titanium peroxy gel on the breakdown of hyaluronan by reactive oxygen species.

The molecular events occurring at the interface between titanium and connective tissue were investigated in order to help explain the unique biocompatible properties of titanium implants and their successful osseointegration into bone tissue. In this study the influence of commercially pure titanium and titanium peroxy gels on the breakdown of the connective tissue component and serum derived factor, hyaluronan, by reactive oxygen species (ROS), produced during the insertion of an implant in vivo, was examined. Hyaluronan breakdown was monitored in vitro in the presence of a hydroxyl radical flux, generated in the presence and absence of titanium powder and discs. Parallel studies examined the breakdown of hyaluronan by hydroxyl radicals in the presence of a titanium peroxy gel, prepared by incubation of the titanium powder or discs in concentrated hydrogen peroxide. The hyaluronan degradation products were separated according to their hydrodynamic size by gel exclusion chromatography. Similarly, experiments were also performed examining the degradation of 2-deoxy-D-ribose by a hydroxyl radical flux in order to demonstrate the detrimental potential of the hydroxyl radicals and to provide a measure of the effectiveness of titanium and titanium peroxy gels as scavengers of ROS. Titanium reduced the harmful effects of the hydroxyl radicals on the breakdown of hyaluronan, presumably acting as a scavenger for the reactive species, possibly by absorbing them into its surface oxide layer, which spontaneously forms on the surface. In contrast, the formation of a titanium peroxy gel from the titanium powder or on the surface of titanium discs enhanced breakdown of both the hyaluronan chains and 2-deoxy-D-ribose. The implications of these findings with regards to the biocompatible nature of the titanium and the ability of these implants to successfully osseointegrate are discussed.

Biocompatible Materials↗
PubMed1995

The chemical modification of glycosaminoglycan structure by oxygen-derived species in vitro.

The effect of reactive oxygen species (ROS) on the chemical structure of glycosaminoglycans (GAG) was studied in order to consider their role in connective tissue damage during an inflammatory disease state such as periodontal disease. GAG were exposed to a radical generating system for 1 h and analysed by gel filtration for fragmentation and chemically with respect to uronic acid, hexosamine and sulfate content. Non-sulfated GAG, hyaluronan and chondroitin, were most susceptible to depolymerisation and chemical modification of uronic acid and hexosamine residues by ROS. Depolymerisation and chemical modification of sulfated GAG, chondroitin 4-sulfate, dermatan sulfate and heparan sulfate was significantly less than for non-sulfated GAG. The highly sulfated GAG heparin showed minimal depolymerisation by ROS, but uronic acid residues were readily modified. Analysis of the ROS-exposed residues suggests that uronic acid is capable of degrading to a 3-carbon aldehyde, malondialdehyde. Chondroitin sulfate exposed to ROS resulted in marginal desulfation. The results suggest that the presence of sulfate on the GAG chain may protect the molecule against ROS attack. However, chemical modification of GAG may affect proteoglycan function and be of importance in considering connective tissue destruction in a variety of pathological situations, including periodontal disease.

Chondroitin Sulfates↗
PubMed1993

Ethical and practical implications of the human genome initiative for family medicine.

Major advances in predictive genetic testing resulting from the Human Genome Initiative could change significantly the routine practice of family medicine. Family physicians should be aware that increased genetic information may affect patients' abilities to acquire and maintain insurance and employment and that interested parties will have incentives to seek this information. The social consequences of genetic information, as well as increased health promotion efforts, may raise problems of informed consent and confidentiality. In addition to their ethical implications, these developments will also affect the practice of family physicians in practical ways such as record keeping. We discuss cases that illustrate the potential impact of these emerging technologies on the practice of family medicine.

Adult↗