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Biomedical subjects

C Neal

Publications and source records attributed to C Neal.

At least 19 recordsLinked to original sources
PubMed2006

The validation of a bioanalytical method for the determination of clopidogrel in human plasma.

A fast, sensitive and specific LC-MS/MS bioanalytical method for the determination of unchanged clopidogrel in human plasma has been developed and validated over the range of 10-12,000 pg mL(-1) (r2 0.9993) by the Contract Research group at HFL. Samples (0.3 mL) were buffered (pH 6.8), extracted using diethyl ether and 10 microL of the sample extract was injected onto the LC-MS/MS system. Analysis was performed using a C8 column (temperature controlled to 50 degrees C) by gradient elution at a flow rate of 0.9 mL min(-1) over a 3 min run time. Retention times of 1.61 and 1.59 min were observed for clopidogrel and 2H3-clopidogrel (I.S.), respectively. Detection was achieved using a Sciex API 4000, triple quadrupole mass spectrometer, in positive TurboIonspray (electrospray) ionisation mode. Ion transitions were monitored using MRM (multiple reaction monitoring) for clopidogrel (m/z 322-212) and for 2H3-clopidogrel (m/z 327-217). This validated method was used to support a pharmacokinetic study in healthy volunteers.

Chromatography, High Pressure Liquid↗
PubMed2006

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders.

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders.

Antidepressive Agents↗
PubMed2005

Chemical behaviour of the Wheal Jane bioremediation system.

The effectiveness of remediation of the highly acidic and transition metal polluted mine water discharge from the Wheal Jane Mine by the Wheal Jane Passive Treatment Plant is described. The success of the remediation required that all the system components work as predicted. The study shows considerable success in the removal of key toxic metals and clearly demonstrates the potential for natural attenuation of acid mine drainage, particularly iron oxidation, by microbial populations. The Wheal Jane Passive Treatment Plant provides the only experimental facility of its kind.

Aerobiosis↗
PubMed2005

Use of a nitrogen arm-stabilized endoscopic microdriver in neuroendoscopic surgery.

Stabilization and manipulation of instruments in endoscopic neurosurgery has traditionally been a manual task. Conventional self-retaining retractors have failed to provide reliable fixation for endoscopic procedures. Most surgeons rely on a team approach to endoscopy with one individual controlling the endoscope while the other manipulates instruments within the field of view. This two-surgeon approach is manpower intensive and not an option at many facilities. Recently developed technology provides the independent practitioner with another option. Several nitrogen-powered stabilizing arms have been introduced which decrease or eliminate problems with post-positioning drift. To facilitate fine maneuvering of the endoscope, a new positioning arm is available with an incorporated microdriver capable of sub-millimeter adjustments. We present an illustrative case of the utility of this device in selected endoscopic procedures.

Adolescent↗
PubMed2003

Seasonality and water quality trends in a maturing recreated reed bed.

The socio-economic and ecological value of wetland ecosystems is widely acknowledged. As a result, considerable efforts are now being made to rehabilitate and in some cases recreate wetlands throughout Europe. An option for the restoration of worked-out peat pits is to establish reed beds. Ham Wall, located in Somerset in the UK, comprises reed bed and a mosaic of other wetland habitats that has been constructed as a wildlife area. Since 1996, water chemistry has been monitored for a 16.5 ha wetland compartment planted with reeds in July 1995. Water is pumped into the reed bed from Ham Wall Rhyne, a drainage ditch supplied with nutrient-rich runoff from the surrounding agricultural land. The principal objectives of the research described in this paper were to investigate differences in the chemistry of water from different locations in the vicinity of the wetland and to evaluate seasonal changes and trends in water quality as the reeds matured. The results obtained provide insight into the biogeochemical functioning of the wetland system.

Conservation of Natural Resources↗
PubMed2003

A summary of boron surface water quality data throughout the European Union.

The distribution of boron in rivers across European Union countries is described. The data have been collected from national and international monitoring programmes. The data show a wide range of concentrations but only in a few instances do concentrations exceed environmental quality standards. Although there is a good body of data for the analysis presented here, it is clear that there is not a full coverage of environments and for some studies there is a clear bias towards sampling of the main rivers or specific rivers where there are environmental concerns. The variations in concentration link directly to pollutant sources although assessment of the details of the spatial variations is clouded by factors such as the location of monitoring points in relation to pollutant discharges, the variation in dilution potential of the various rivers and contrasting hydrological and geological environments. The data are presented to complement more detailed studies on particular river basins as a basis for the further development of regional environmental impact water quality modelling frameworks and within the newly developing field of typological settings.

Journal Article↗
PubMed2003

Henoch-Schönlein purpura following hepatitis B vaccination.

The use of recombinant hepatitis B vaccines has led to the effective prevention of hepatitis B infection and its chronic sequelae in immunocompetent individuals. Whilst rare, a variety of serious adverse effects have been reported following vaccination including cutaneous vasculitis in eight previous cases. We describe a case of Henoch-Schönlein purpura developing after hepatitis B vaccination.

Adult↗
PubMed2003

Measuring in-stream productivity: the potential of continuous chlorophyll and dissolved oxygen monitoring for assessing the ecological status of surface waters.

Continuous (hourly) measurements of dissolved oxygen and chlorophyll (determined by fluorimetry) were made for an inter-linked lowland river and canal system. The dissolved oxygen data were used to estimate daily rates of re-aeration, photosynthesis and respiration, using a process-based analytical technique (the Delta method). In-situ fluorimeter measurements of chlorophyll were ground-truthed on a fortnightly basis using laboratory methanol extraction of chlorophyll and spectrophotometric analysis. Water samples were also analysed for algal species on a fortnightly basis. The river and canal exhibited very similar rates of photosynthesis and respiration during the summer of 2001, despite much higher chlorophyll concentrations and total algal counts, indicating that benthic algae and/or aquatic macrophytes may be making an important contribution to photosynthesis rates in the river. Suspended algal populations in the canal are dominated by planktonic species, whereas the river has a higher proportion of species which are predominantly benthic in habitat. The river exhibited higher rates of respiration, reflecting a higher organic loading from external (e.g. sewage effluent) sources.

Chlorophyll↗
PubMed2002

Calcite saturation in the River Dee, NE Scotland.

The spatial and temporal variations in calcite (calcium carbonate) solubility within the Dee basin of NE Scotland were assessed using water chemistry data gathered from a network of 59 sites monitored for water quality from June 1996 to May 1997. Calcite solubility, expressed in terms of a saturation index (SIcalcite), was determined from measured streamwater pH, Gran alkalinity and calcium concentrations and water temperature. In general, the waters of the Dee system are undersaturated with respect to calcite, though the saturation index is higher during the summer months indicating a dependency on flow conditions and biological activity. Under low-flow conditions, the streamwaters are dominated by water derived from the lower soil horizons and deeper groundwater stores and therefore, ions such as Gran alkalinity and calcium are at their highest concentrations as they are derived mainly from bedrock weathering. The influence of biological activity on the carbonate system is also evident as the observed pH and estimated EpCO2 values indicate strong seasonal patterns, with the highest pH and lowest EpCO2 values occurring during the summer low-flow periods. Only at three sites in the lowland region of the catchment, during the summer low-flow period, are the waters oversaturated. As such, the Dee system represents an extreme 'end-member' case when compared to many UK rivers that span both under- and oversaturated conditions during the year. Regression analysis highlights a systematic change in the SIcalcite-pH relationship in a broad east-west direction across the Dee system. At sites draining the relatively impermeable upland areas, the regression of SIcalcite against pH gives a straight line with a gradient in the range 1.6-2.4. Correspondingly, under the most extreme alkaline conditions found at sites draining lowland agricultural areas, a straight-line relationship exists but with a gradient of unity. It is concluded that these changes in the SIcalcite-pH relationship are due to variations in the bicarbonate system induced by the flow conditions and biological activity. Given the waters are undersaturated, then calcite precipitation and hence phosphorus co-precipitation cannot occur within the water column.

Agriculture↗
PubMed2002

Phosphorus uptake into algal biofilms in a lowland chalk river.

This paper examines the growth and uptake of phosphorus into algal biofilms in the River Kennet, a lowland chalk (Cretaceous-age) stream in southern England. Algal biofilms were grown on artificial plastic substrates (templates) placed (i) on the riverbed and (ii) within the mid-water column. Experiments were set up to examine differences in growth rates of newly colonising biofilms compared with biofilms left to accumulate for periods of up to 6 months. Rates of algal biofilm production were measured by the chlorophyll a concentration that had accumulated per cm2 over the number of days that the biofilm template had been immersed in the river water. An algal biofilm bloom occurred in early spring, prior to peak suspended chlorophyll a concentrations within the water column. Biofilm samples collected in February and March had the highest chlorophyll a and total phosphorus concentrations. The biofilm bloom corresponded with increased solar radiation and declining river flow conditions. Periodic increases in soluble reactive phosphorus concentrations in the overlying river water did not correspond with any significant increase in biofilm production. These results suggest that light, rather than phosphorus is a key factor for biofilm growth in the River Kennet. Higher rates of chlorophyll a development in mid-water column biofilms may be linked to greater light exposure; however, maximum total-P concentrations were similar for both bed and water column biofilms. Newly colonising biofilms exhibited higher chlorophyll a and total-P concentrations than biofilms left to accumulate over longer terms, suggesting that fresh substrate availability promotes high rates of biofilm growth. Both 'condensed and organic' P (stored in biomass) and 'inorganic' (mineral) P fractions within the biofilms were present in varying proportions, although the early spring biofilm bloom resulted in maximum proportions and absolute concentrations of 'condensed and organic' P. Calcite was the only crystalline mineral detected within the biofilms. Ratios of Ca:inorganic P are largely consistent with the presence of CaCO3-P co-precipitates, although one very low value suggested that there may also be additional sources of inorganic P, possibly P adsorbed to clays or organics within the biofilm. However, poor linkages between CaCO3 and inorganic P concentrations suggest that, although the inorganic P fraction within the biofilm may be derived largely from CaCO3-P co-precipitation, the subsequent processes controlling overall CaCO3 and inorganic P concentrations in the biofilm are complex.

Biofilms↗
PubMed2001

An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins and is required for G(o)-mediated signal transduction.

The P2Y(2) nucleotide receptor (P2Y(2)R) contains the integrin-binding domain arginine-glycine-aspartic acid (RGD) in its first extracellular loop, raising the possibility that this G protein-coupled receptor interacts directly with an integrin. Binding of a peptide corresponding to the first extracellular loop of the P2Y(2)R to K562 erythroleukemia cells was inhibited by antibodies against alpha(V)beta(3)/beta(5) integrins and the integrin-associated thrombospondin receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged P2Y(2)Rs indicated that alpha(V) integrins colocalized 10-fold better with the wild-type P2Y(2)R than with a mutant P2Y(2)R in which the RGD sequence was replaced with RGE. Compared with the wild-type P2Y(2)R, the RGE mutant required 1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase, activate extracellular signal-regulated kinases, and initiate the PLC-dependent mobilization of intracellular Ca(2+). Furthermore, an anti-alpha(V) integrin antibody partially inhibited these signaling events mediated by the wild-type P2Y(2)R. Pertussis toxin, an inhibitor of G(i/o) proteins, partially inhibited Ca(2+) mobilization mediated by the wild-type P2Y(2)R, but not by the RGE mutant, suggesting that the RGD sequence is required for P2Y(2)R-mediated activation of G(o), but not G(q). Since CD47 has been shown to associate directly with G(i/o) family proteins, these results suggest that interactions between P2Y(2)Rs, integrins, and CD47 may be important for coupling the P2Y(2)R to G(o).

Amino Acid Sequence↗
PubMed2001

The environmental impact of heavy metals from sewage sludge in ferralsols (São Paulo, Brazil).

The spreading of sewage sludge on acidic ferralsol soil was simulated in a column experiment in order to estimate the potential impact on water and soil quality. Drainage and runoff water were sampled daily over a 2-month experiment and analysed for Fe, Ni, Cu, Pb and DOC. Results show a clear influence of the sludge on the water quality, especially at the start of the experiment, increasing the export of Cu, Ni, Pb and in DOC from the soil, mainly in dissolved form. Nickel was usually the most mobile element in the sludge and in the soil. In the soil, Pb mobility was complex and increased drastically with time compared to the other elements. No significant increase in soil heavy metal content due to the sludge spreading was recorded on this time scale.

Agriculture↗
PubMed2001

Use of continuous water quality records for hydrograph separation and to assess short-term variability and extremes in acidity and dissolved carbon dioxide for the River Dee, Scotland.

A combination of continuous (15-min) pH, conductivity and temperature measurements and fortnightly spot-sampled water quality data were used to examine temporal variability and extremes in river water quality in an upland Scottish river: the River Dee at Mar Lodge. An empirical relationship was established for Gran-alkalinity by multiple regression against flow and conductivity for the fortnightly data. Applying this relationship to the continuous data, an estimate of continuous Gran-alkalinity was calculated. The continuous Gran-alkalinity record was used as (1) a conservative tracer in a simple two-component mixing model to determine the relative proportions of near-surface runoff and deeper groundwater contributing to stream flow; (2) to deconvolute the contribution of weathering and sea-salt contributions to stream conductivity; and (3) to calculate the excess partial pressure of carbon dioxide in stream water. The episodic variations in pH, weathering and sea-salt conductivity and excess partial pressures of carbon dioxide (EpCO2) associated with high flow events in the River Dee suggest that hydrological pathways play an important role in determining stream chemistry. The results of the hydrograph separation indicate that groundwater provides an important contribution to stream flow, and that there are large and hydrologically active stores of groundwater within the upper River Dee catchment. Sea-salts have an important influence on stream conductivity, particularly with the onset of storm runoff following summer drought periods. This suggests that sea-salts are concentrated in the upper soil horizons by dry deposition and/or evapotranspiration. EpCO2 behaves non-conservatively and shows marked diurnal variability under low-flow conditions during summer, inducing diurnal pH variations, and indicating the importance of within-river biological processes. This study emphasises the very intermittent nature of water quality extremes with stream spates and the diurnal nature of biologically-induced responses. Fortnightly sampling programmes do not capture the range of high flow extremes, and with sampling undertaken during the working day, biological extremes occurring at night are also missed, introducing bias. This study shows the value of continuous measurements for infilling aspects of these intermittent extremes. However, it is also noted that the relatively simple patterns of response observed from the continuous measurements may well belie a much more varied response at the sub-catchment and hillslope scales, as local chemical and hydrological heterogeneities do occur. Thus, the two-component mixing model used is, in practice, based on catchment integrated values for a range of soil water and groundwater endmembers.

Carbon Dioxide↗
PubMed2001

Alkalinity measurements within natural waters: towards a standardised approach.

A discussion on the measurement of alkalinity in bicarbonate bearing and acidic waters is presented as a move towards developing a standardised approach within the aquatic sciences. The discussion is based on theoretical and practical considerations. Practical illustrations are provided from measurements of calcium bicarbonate bearing waters (River Thames) and acidic to near neutral waters from acidic soil systems with calcium bearing groundwater sources (the mid-Wales region and the Scottish Dee basin). A comparison of single endpoint and Gran procedures is made and the various error terms assessed. It is concluded that single endpoint and Gran methodologies are applicable in the standard pH titration used in aquatic research (pH 4.5-4.0). However, analytical errors increase, particularly for the single endpoint titration, the lower the endpoint/endpoint-range in pH. For the Thames, the value of a single endpoint over a Gran procedure is illustrated. The Thames results show that some buffering components may still be titrated out within the Gran titration range used: this leads to an underestimate in the alkalinity. Indeed, by making a comparison between single endpoint and Gran alkalinity measurements, the Thames results indicated the presence of unexpected buffering components: the interrogative nature of this type of analysis is highlighted. A standardised approach is outlined.

Animals↗
PubMed2001

Environmental change, land use and water quality in Scotland: current issues and future prospects.

An outline of both the scientific and management needs facing the future water quality issues of Scotland is discussed. The scientific needs are considered in terms of monitoring to increase the understanding of hydrochemical processes, issues of scaling, and the need for improved modelling under changing environmental processes. In terms of the management needs, the requirements highlighted relate to improving the ecological quality of Scottish rivers and the implementation of integrated river basin management plans.

Agriculture↗
PubMed2001

Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering?

The luminal surface of endothelial cells is lined with the glycocalyx, a network structure of glycoproteins probably 50 to 100 nm thick. It has been suggested that a relatively regular fibre-matrix structure may be responsible for the ultrafiltration properties of microvascular walls, both when the endothelium is continuous and when it is fenestrated. Positive structural evidence demonstrating an underlying periodicity in the glycocalyx has been hard to obtain. Here we present structural analysis of glycocalyx samples prepared in a variety of ways for electron microscopy. Using computed autocorrelation functions and Fourier transforms of representative areas of the electron micrograph images, we show that there is an underlying three-dimensional fibrous meshwork within the glycocalyx with characteristic spacings of about 20 nm. Together with a fibre diameter consistent with our observations of about 10-12 nm, the 20-nm spacing provides just the size regime to account satisfactorily for the observed molecular filtering; the observations are consistent with the fibre matrix model. We also show that the fibrous elements may occur in clusters with a common intercluster spacing of about 100 nm and speculate that this may reveal organisation of the glycocalyx by a quasi-regular submembranous cytoskeletal scaffold.

Animals↗
PubMed2001

Widespread collaboration of Isw2 and Sin3-Rpd3 chromatin remodeling complexes in transcriptional repression.

The yeast Isw2 chromatin remodeling complex functions in parallel with the Sin3-Rpd3 histone deacetylase complex to repress early meiotic genes upon recruitment by Ume6p. For many of these genes, the effect of an isw2 mutation is partially masked by a functional Sin3-Rpd3 complex. To identify the full range of genes repressed or activated by these factors and uncover hidden targets of Isw2-dependent regulation, we performed full genome expression analyses using cDNA microarrays. We find that the Isw2 complex functions mainly in repression of transcription in a parallel pathway with the Sin3-Rpd3 complex. In addition to Ume6 target genes, we find that many Ume6-independent genes are derepressed in mutants lacking functional Isw2 and Sin3-Rpd3 complexes. Conversely, we find that ume6 mutants, but not isw2 sin3 or isw2 rpd3 double mutants, have reduced fidelity of mitotic chromosome segregation, suggesting that one or more functions of Ume6p are independent of Sin3-Rpd3 and Isw2 complexes. Chromatin structure analyses of two nonmeiotic genes reveals increased DNase I sensitivity within their regulatory regions in an isw2 mutant, as seen previously for one meiotic locus. These data suggest that the Isw2 complex functions at Ume6-dependent and -independent loci to create DNase I-inaccessible chromatin structure by regulating the positioning or placement of nucleosomes.

Adenosine Triphosphatases↗