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C Exley

Publications and source records attributed to C Exley.

31 records · Page 2Linked to original sources
PubMed1996

Speciation of aluminum in biological systems.

As a "hard", trivalent metal ion, Al3- binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular mass fraction of serum Al. The lability of the Al3+ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as 27Al-NMR and accelerator mass spectrometry with 26Al; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin at 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.

Aluminum↗
PubMed1996

Kinetic constraints in acute aluminium toxicity in the rainbow trout (Oncorhynchus mykiss).

We have designed a laboratory bioassay to expose fish to kinetically determined differences in aluminium hydroxide solution chemistry. We have used this system to demonstrate the hitherto unexpected result of an acute aluminium toxicity in the fish at a pH of 6.5. Supporting experiments have demonstrated that the mechanism of toxicity at this pH was probably an asphyxiation brought about by aluminium-induced changes in the rheological and diffusional properties of the mucus lining of the gill epithelium.

Aluminum↗
PubMed1996

Attitudes and beliefs within the Sikh community regarding organ donation: a pilot study.

The current shortage of organs for transplantation is a matter of considerable concern in the United Kingdom (U.K.). Whilst issues of histocompatibility create particular problems in this respect for the Asian population in the U.K., it is sometimes suggested that there is also a resistance to the idea of organ transplantation among this community. To explore this issue, a small-scale interview study was conducted in Coventry among members of the Sikh community. A judgemental sample of 22 individuals, from different strata of the local Sikh community, were interviewed either in one-to-one interviews or in a focus group. These interviews had two broad aims: to determine the prevailing attitudes towards organ transplantation, and to gauge the impact and acceptability of the current Department of Health campaign literature. It was found that, whilst there were a number of misgivings to do with notions of mutilation and reincarnation, and anxieties as to technical or clinical aspects of the transplantation process, the prevailing view was supportive of transplantation, and organ donation was seen as a highly appropriate means of exhibiting the altruistic tradition within Sikhism. Such barriers that exist to the idea of transplantation seem to have more to do with knowledge and understanding than with cultural or religious factors. Concerning the campaign literature, informants identified a number of shortcomings, and indicated ways in which the impact of the leaflets and posters might be enhanced. Although the generalizability of these findings is limited, and despite possible threats to the validity of the data collected, this study has produced findings with significant implications for future policy in this area.

Ethnicity↗
PubMed1996

The admission of Asian patients to intensive therapy units and its implications for kidney donation: a preliminary report from Coventry, UK.

OBJECTIVE: To determine the relative admission rates of Asian and non-Asian patients to intensive therapy units (ITUs) in Coventry and to explore the implications of these rates for the transplantation of organs to Asian people. DESIGN: Examination of 1991 census data and a retrospective review of ITU admissions books. Data were collected on ethnic background, presenting diagnosis, and clinical outcome for each admission. SETTING: The three ITUs in Coventry. PATIENTS: All admissions to the ITUs from 1990-93 inclusive. RESULTS: Asian patients were admitted to ITUs disproportionately to their numbers in the Coventry population. Members of the Asian community were less than half as likely to be admitted to an ITU (p < 0.001) and more likely to die while there (p = 0.007) than members of the non-Asian population in Coventry. The proportions of patients referred to the transplant unit and the rates of subsequent donation do not seem to differ significantly for Asian and non-Asian patients (p = 0.26 in both cases). CONCLUSIONS: There are clear implications for the availability of cadaveric kidney transplantation to Asian patients, given that few kidneys from non-Asian donors are histocompatible with Asian recipients. Indeed, in Asians, promotion of living related donation may be more effective in countering the organ shortfall than efforts to increase consent to cadaveric transplantation. However, it may be valuable to investigate any patterns of morbidity or social or cultural factors that might explain the initial low admissions rates to ITUs for Asian patients.

Asia↗
PubMed1995

Aluminium, beta-amyloid and non-enzymatic glycosylation.

The non-enzymatic glycosylation of beta-amyloid is implicated in the aetiology of Alzheimer's disease. However, controversy surrounds the nature of any involvement and a potential mechanism has not been fully elucidated. We present evidence of an aluminium-induced aggregation of the A beta P(25-35) peptide and speculate that the mechanism of formation of our ordered beta-amyloid aggregates might involve non-enzymatic glycosylation and/or site-specific crosslinking of beta-amyloid fibrils by atomic aluminium.

Aluminum↗
PubMed1994

Aluminum inhibition of hexokinase activity in vitro: a study in biological availability.

We have used the HK/G6PDH coupled enzyme assay to determine the biological availability of aluminum in mixed-ligand media of biological interest. The biological availability of aluminum was measured as the inhibition of the activity rate of the assay and was shown to be dependent upon the equilibration state of the aluminum stock solutions (prior to their addition to the assay) and the comparative reaction kinetics of competitive aluminum equilibria in the assays. Aluminum was found to inhibit the assay, however, the inhibition by aluminum was abolished when silicic acid was present in both the aluminum stock solution and the assay medium. The assay is proposed as a model system for investigating the biological availability of aluminum in heterogenous media of biochemical significance.

Aluminum↗
PubMed1993

An interaction of beta-amyloid with aluminium in vitro.

We have used circular dichroism spectroscopy to confirm that, in a membrane-mimicking solvent, A beta P(1-40) adopts a partially helical conformation and we have demonstrated the loss of this structure in the presence of physiologically relevant concentrations of aluminium. This is the first evidence of a direct biochemical interaction between aluminium and beta-amyloid and may have important implications for the pathogenesis of Alzheimer's disease.

Aluminum↗
PubMed1992

The cellular toxicity of aluminium.

Aluminium is a serious environmental toxicant and is inimical to biota. Omnipresent, it is linked with a number of disorders in man including Alzheimer's disease, Parkinson's dementia and osteomalacia. Evidence supporting aluminium as an aetiological agent in such disorders is not conclusive and suffers principally from a lack of consensus with respect to aluminium's toxic mode of action. Obligatory to the elucidation of toxic mechanisms is an understanding of the biological availability of aluminium. This describes the fate of and response to aluminium in any biological system and is thus an important influence of the toxicity of aluminium. A general theme in much aluminium toxicity is an accelerated cell death. Herein mechanisms are described to account for cell death from both acute and chronic aluminium challenges. Aluminium associations with both extracellular surfaces and intracellular ligands are implicated. The cellular response to aluminium is found to be biphasic having both stimulatory and inhibitory components. In either case the disruption of second messenger systems is observed and GTPase cycles are potential target sites. Specific ligands for aluminium at these sites are unknown though are likely to be proteins upon which oxygen-based functional groups are orientated to give exceptionally strong binding with the free aluminium ion.

Aluminum↗
PubMed1991

A mechanism for acute aluminium toxicity in fish.

Aluminium is acutely toxic to fish in acid waters. The gill is the principal target organ and death is due to a combination of ionoregulatory, osmoregulatory and respiratory dysfunction. The toxic mechanism has hitherto received little direct consideration and is unknown. In this paper the mechanism of acute aluminium toxicity is approached from a chemical perspective. Symptomatic evidence of toxicity is taken from the literature and combined with our own research to elucidate a biochemically sound model to describe a possible mechanism of acute aluminium toxicity in fish. The proposed model delineates the chemical conditions immediately adjacent to the gill surface and emphasizes their importance in aluminium's toxic mode of action. The mechanism is shown to be bipartite. Aluminium binding to functional groups both apically located at the gill surface and intracellularly located within lamellar epithelial cells disrupts the barrier properties of the gill epithelium. The concomitant iono- and osmoregulatory dysfunction results in accelerated cell necrosis, sloughing and death of the fish. The mechanism of epithelial cell death is proposed as a general mechanism of aluminium-induced accelerated cell death.

Acid Rain↗