Search PubMed⌕ Search

Biomedical subjects

W R Ferrell

Publications and source records attributed to W R Ferrell.

95 records · Page 6Linked to original sources
PubMedDate not supplied

Nerve-mediated responses of blood vessels in the rabbit knee joint.

Blood vessels in the anterior region of the knee joint of anaesthetised rabbits showed a biphasic response to the electrical stimulation (10 Hz, 1 ms width, 10 V amplitude) of nerve fibres supplying the knee, as measured by laser Doppler flowmetry. The response consisted of vasoconstriction during nerve stimulation followed by a prolonged dilatation. The vasoconstrictor response was mediated by noradrenaline acting mainly via alpha 1-adrenoceptors as it was substantially reduced by close intra-arterial injection of the alpha-adrenergic antagonist phentolamine (approximately 50% reduction) and the selective alpha 1-adrenergic antagonist prazosin (approximately 50% reduction) but not by the alpha 2-antagonist rauwolscine. Further studies involving prolonged (2-hour) close intra-arterial infusion of prazosin gave a approximately 50% reduction of the constrictor response with a concentration of 10(-5) M and approximately 95% reduction when the concentration was raised to 10(-4) M. At the higher prazosin concentration responses to close intra-arterial injection of the alpha 1-agonist phenylephrine were substantially reduced but responses to the alpha 2-agonists clonidine and UK-14304 were not significantly influenced. Infusions of the alpha 2 antagonist CH 38083 failed to inhibit nerve-mediated vasoconstriction at 10(-5) or 10(-4) M. There did not appear to be a purinergic component, as the constrictor response was unaffected by the P2X desensitiser alpha,beta-methylene adenosine 5'-triphosphate. The dilator response appeared to be mediated principally by substance P (presumably released from sensory C fibers) as it was substantially reduced by intraarticular injection of substance P antagonist D-Pro4D-Trp7,9,10-SP(4-11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Laser Doppler perfusion imaging of synovial tissues using red and near infra-red lasers.

A new laser Doppler perfusion imaging (LDI) system was evaluated by comparing it with the well-established radiolabelled microsphere technique for measuring blood flow in the rabbit knee joint capsule. In this study two laser sources (635 and 835 nm) were compared at three scan speeds (50, 10 and 4 ms/pixel). With blood flow to the rabbit hindlimb controlled via a peristaltic pump, the comparison of LDI and microsphere measurement techniques yielded highly significant correlations for both laser sources (r = 0.9; p = 0.0001; 14 measurements in 7 animals). Comparison of the three scan speeds demonstrated acceptable agreement without significant bias between measurements, suggesting that the inevitable narrowing of the bandwidth at the fastest scan speed does not cause significant deterioration of the signal. The flux values obtained with 635 and 835 nm laser sources were linearly related (r = 0.93, p = 0.0001; 66 measurements in 12 animals), although there was a small but significant bias for higher values with the 635-nm laser (mean ratio of flux values 1.06, 95% confidence interval 1.01-1.12). These results validate the use of LDI with either wavelength laser for the assessment of joint capsule perfusion.

Animals↗
PubMedDate not supplied

Combined inhibition of nitrergic and prostanoid pathways in J774 macrophages.

OBJECTIVES: Nitric oxide and prostaglandins are both implicated in the pathogenesis of inflammatory conditions such as rheumatoid arthritis (RA). The hypothesis that simultaneous inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) was more effective than inhibition of either enzyme alone was tested. METHODS: J774 macrophages were pre-incubated with L-NAME and/or indomethacin, prior to activation with LPS (10 micrograms/ml). RESULTS: LPS significantly increased NO2-; PGE2 and TNF-alpha levels by 24 h. Quantitative real-time PCR demonstrated a dose-dependent reduction in the expression of COX-2 in the presence of increasing doses of L-NAME. NO2- and PGE2 production were inhibited in a dose-dependent manner by either indomethacin or L-NAME. Combined administration of L-NAME and indomethacin produced a significantly greater inhibition of NO2- and PGE2 than either inhibitor alone. CONCLUSION: The data supports the therapeutic potential of combined inhibition of the prostanoid and nitrergic systems as an anti-inflammatory treatment strategy and supports the progression of this work into models of arthritis.

Cells, Cultured↗
PubMedDate not supplied

Laser Doppler perfusion imaging of proximal interphalangeal joints in patients with rheumatoid arthritis.

OBJECTIVE: A non-invasive imaging technique (laser Doppler perfusion imaging-LDI) based on measurement of backscattered Doppler-broadened near infra-red laser radiation was used to provide two-dimensional images of perfusion over the proximal interphalangeal (PIP) joints of a group of normal subjects compared to a group of patients with rheumatoid arthritis (RA). RESULTS: Some PIP joints of the RA group showed areas of increased perfusion whereas normal subjects showed much less variation in perfusion between joints. These hyperaemic areas arose from the underlying joint, as scans taken with a less penetrating red laser did not show such areas. CONCLUSION: Apart from its obvious dermatological uses, LDI could be employed to image hyperaemia associated with a variety of inflammatory conditions affecting subcutaneous structures.

Adult↗