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Biomedical subjects

Alun D Hughes

Publications and source records attributed to Alun D Hughes.

8 recordsLinked to original sources
PubMed2003

Only weak vasorelaxant properties of loop diuretics in isolated resistance arteries from man, rat and guinea pig.

Besides their diuretic action, loop diuretics may induce a rapid vasodilator effect that contribute to their short-term therapeutic properties. We examined the effects of furosemide (10(-6)-10(-3) mol l(-1)) in comparison with bumetanide (10(-6)-10(-4) mol l(-1)) on isolated resistance arteries from rat and guinea pig mesentery and human subcutaneous fat, and investigated the mechanism of the acute direct vasorelaxant action on an isometric microvascular myograph. Both loop diuretics induced concentration-dependent relaxation of resistance vessels irrespective of membrane potential. The maximal effect of furosemide was greatest in rat and least in human arteries. Both diuretics caused a rightward shift in the concentration-response curve to extracellular Ca(2+). Incubation with indomethacin (2 x 10(-5) mol l(-1)) or mechanical removal of the endothelium did not inhibit the loop diuretic-induced relaxation. At high concentrations (10(-4)-10(-3) mol l(-1)) loop diuretics exert only weak direct relaxant effects on isolated human subcutaneous resistance arteries compared to the vasorelaxant effects in rat and guinea pig mesenteric vessels.

Animals↗
PubMed2002

Thrombospondin-1 differentially induces chemotaxis and DNA synthesis of human venous smooth muscle cells at the receptor-binding level.

Thrombospondin-1 is a large matricellular protein that acts as a pleiotropic growth factor for human vascular smooth muscle cells, and may play a role in the progression of vascular disease. Although we have previously demonstrated the dependence of both thrombospondin-1-stimulated cell chemotaxis and proliferation on tyrosine kinases, the receptor mechanisms involved remain obscure. This investigation aims to determine the nature of the receptor(s) involved in the cellular responses to thrombospondin-1. Cellular signals were identified by western blotting following cell stimulation, while cellular responses were assessed by measuring DNA synthesis and chemotaxis. These data demonstrate that thrombospondin-1-induced cell chemotaxis can be inhibited by a peptide containing the Arg-Gly-Asp motif, a function-blocking alpha(v)beta(3) antibody, a function-blocking integrin-associated protein (IAP) antibody and pertussis toxin, while thrombospondin-1-stimulated DNA synthesis is inhibited by a function-blocking alpha(3)beta(1) antibody. Similarly the Arg-Gly-Asp-containing peptide inhibits tyrosine phosphorylation of focal adhesion kinase and the p85 regulatory subunit of phosphatidylinositol 3-kinase, but does not significantly affect tyrosine phosphorylation, or activation, of extracellular-regulated kinase. These data suggest that soluble thrombospondin-1 interacts with human vascular smooth muscle cells via two independent and separable receptor-binding sites, to differentially stimulate cell chemotaxis and DNA synthesis.

Antibodies↗
PubMed2002

Ethnic differences in carotid and left ventricular hypertrophy.

OBJECTIVES: Afro-Caribbean subjects have a higher prevalence of hypertension, a lower prevalence of ischaemic heart disease and a higher premature mortality compared to White Europeans. Left ventricular hypertrophy (LVH) is also more prevalent in Afro-Caribbeans even at similar levels of blood pressure. It is widely believed that carotid artery intima-media thickening (IMT) represents an early marker for the development of atheroma, and carotid IMT and LVH are associated in White populations. Whether the relationship between carotid IMT and LVH is similar in Black subjects is unknown. METHODS: Thirty-eight subjects were studied using carotid and femoral ultrasonography and echocardiography; 19 Afro-Caribbean and 19 White European subjects were matched for age, sex and mean 24 h systolic blood pressure. RESULTS: The Afro-Caribbean group had a significantly greater left ventricular mass index (LVMI) compared to the White European: 136.4 +/- 6.1 versus 112.4 +/- 6.2 g/m2, P < 0.01. However, carotid IMT, carotid diameter, femoral IMT and femoral diameter were similar between the groups: 0.75 +/- 0.02 versus 0.77 +/- 0.04 mm, 6.54 +/- 0.15 versus 6.56 +/- 0.16 mm, 0.66 +/- 0.03 versus 0.68 +/- 0.03 mm and 8.40 +/- 0.33 versus 8.25 +/- 0.23 mm, respectively. CONCLUSIONS: Afro-Caribbean subjects with similar blood pressures have similar mean carotid and femoral IMTs compared to White Europeans, in spite of marked differences in LVMI. Whether this reflects a discrepancy in the degree of cardiovascular risk for similar levels of LVMI or whether this is a reflection of an altered pattern of target organ damage associated with hypertension in Afro-Caribbean subjects is unclear.

Adult↗
PubMed2002

Retinal vascular tree morphology: a semi-automatic quantification.

A semi-automatic method to measure and quantify geometrical and topological properties of continuous vascular trees in clinical fundus images is described. Measurements are made from binary images obtained with a previously described segmentation process. The skeletons of the segmented trees are produced by thinning,ff branch and crossing points are identified and segments of the trees are labeled and stored as a chain code. The operator selects a tree to be measured and decides if it is an arterial or venous tree. An automatic process then measures the lengths, areas and angles of the individual segments of the tree. Geometrical data and the connectivity information between branches from continuous retinal vessel trees are tabulated. A number of geometrical properties and topological indexes are derived. Vessel diameters and branching angles are validated against manual measurements and several derived geometrical and topological properties are extracted from red-free fundus images of ten normotensive and ten age- and sex-matched hypertensive subjects and compared with previously reported results.

Adult↗
PubMed2002

Measurement of hemodynamics in human carotid artery using ultrasound and computational fluid dynamics.

The objective of the study was to investigate the feasibility of using computational fluid dynamic modeling (CFD) with noninvasive ultrasound measurements to determine time-variant three-dimensional (3D) carotid arterial hemodynamics in humans in vivo. The effects of hyperoxia and hypoxic hypercapnia on carotid artery local hemodynamics were examined by use of this approach. Six normotensive volunteers followed a double-blind randomized crossover design. Blood pressure, heart rate, and carotid blood flow were measured while subjects breathed normal air, a mixture of 5% CO(2) and 15% O(2) (hypoxic hypercapnia), and 100% O(2) (hyperoxia). Carotid artery geometry was reconstructed on the basis of B-mode ultrasound images by using purpose-built image processing software. Time-variant 3D carotid hemodynamics were estimated by using finite volume-based CFD. Systemic blood pressure was not significantly affected by hyperoxia or hypoxic hypercapnia, but heart rate decreased significantly with hyperoxia. There was an increase in diastolic flow velocity in the external carotid artery after hypoxic hypercapnia, but otherwise carotid blood flow velocities did not change significantly. Compared with normal air, hyperoxic conditions were associated with a decrease in the width of the region of flow separation in the external carotid artery. During hyperoxia, there was also an increase in the minimum and a decrease in maximum shear stress in the bifurcation and hence a reduction in cyclic variation in shear stress. Hypoxic hypercapnia was associated with a reduced duration of flow separation in the external carotid artery and an increase in the minimum shear stress without affecting the cyclic variation in shear stress. This study demonstrates the feasibility of using noninvasive ultrasound techniques in conjunction with CFD to describe time-variant 3D hemodynamics in the human carotid arterial bifurcation in vivo.

Adult↗
PubMed2002

Is carotid artery intima-media thickening a reliable marker of early atherosclerosis?

BACKGROUND: It is widely believed that carotid artery intima-media thickening represents an early marker for the development of atheroma. However, carotid intima-media thickening might also be expected to occur in response to an increased tensile stress and decreased wall shear stress which may accompany physical exercise. DESIGN, METHODS, AND RESULTS: In order to test this hypothesis 24 athletes (professional footballers) were compared to 14 age and sex matched control subjects. Each subject underwent carotid and femoral ultrasonography and echocardiography. The athletes had a greater left ventricular mass index compared with the controls: 135 (127-143) vs. 104 (91-116) g/m2, p < 0.001. In addition, they had a greater carotid intima-media thickness (IMT): 0.55 (0.52-0.57) vs. 0.51 (0.48-0.54) mm, p < 0.05. However, carotid artery diameters, femoral IMT and femoral artery diameters were similar: 6.0 (5.9-6.2) vs. 5.8 (5.6-6.1) mm, 0.43 (0.42-0.45) vs. 0.43 (0.41-0.45) mm and 8.3 (8.0-8.6) vs. 8.4 (8.0-8.7) mm, respectively. CONCLUSIONS: The increased carotid IMT of the athletes may result from intermittent exposure to markedly elevated systemic arterial pressures during exercise, resulting in intermittent elevations in carotid wall tensile stress. The lack of a disparity between athletes and controls for femoral IMT may be explained by the intermittent elevation of femoral wall tensile stress being accompanied by increased femoral artery blood flow and wall shear stress, which would tend to reduce any wall thickening. This is an important observation, since it suggests that an increased carotid IMT cannot be relied on solely as a marker of early atherosclerosis.

Adolescent↗
PubMed2002

The antimitogenic action of the sulphated polysaccharide fucoidan differs from heparin in human vascular smooth muscle cells.

The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth muscle cell (VSMC) proliferation. In this study we compared their actions on mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell surface [3H]-heparin binding with similar affinity, they exerted clearly distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic action of serum and thrombospondin- I (though less potently than fucoidan), but failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan, but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan inhibited serum-induced mitogenesis in "heparin resistant" VSMC, which are refractory to heparin's antimitogenic action. In summary, the structurally different polysaccharides, heparin, fucoidan (and fucans) have distinguishable effects on mitogenesis and ERK1/ERK2 activation, suggesting that different mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan and its efficacy in heparin resistant VSMC emphasise the need to further investigate its mechanism of action in human VSMC and suggest this agent could have therapeutic potential.

Animals↗