Stephen Daniels

• Cardiff University

[18F]F-DOPA is an important radiotracer that is used in the diagnosis of Parkinson's disease and neuroendocrine tumours. We describe a simple synthesis for a number of diaryliodonium salt precursors that are suitable for the production of [18F]F-DOPA through reaction with no carrier added (n.c.a.) nucleophilic [18F]fluoride. The simple procedure gi...

Importance of the field: Positron emission tomography (PET) is rapidly emerging as the functional imaging method of choice for in vivo imaging applications in a number of key areas of drug discovery and clinical pathology, but especially in oncology. One key limitation of PET is the requirement for rapid synthesis and purification of biomarker/dru...

The observed cellular effects of pressure are entirely compatible with the acute manifestations of CNS hyperexcitability. Inhibition of the glycine receptor will reduce post-synaptic inhibition, leading to increased excitability (cf 'Startle Disease', an hereditary disease with increased excitability arising from a genetic modification to the glyci...

FMLP stimulation of Xenopus oocytes expressing fMLP receptors leads to a concentration-dependent biphasic inward current. To identify the evolution of these currents we have examined the effects of blocking various cell signalling pathways. In addition we have analysed the effects of three intravenous anaesthetics on these fMLP-induced currents. Xe...

To elucidate potential stereoselective effects of single barbiturate isomers, we compared the inhibitory potency of single thiopentone enantiomers, two isomer-enriched mixtures of methohexitone and racemic mixtures of both barbiturates on the fMLP-induced neutrophil oxidative response. A suppression of the response to 50% compared to control requir...

To test whether there is a common site of action for intravenous anaesthetics at the glycine receptor, the effects of binary combinations of thiopentone, pentobarbitone, methohexitone, and propofol have been tested on human alpha(1) glycine receptors expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. Thiopentone (5-40...

N‐formyl peptides (e.g. fMLP; N‐formyl‐ L ‐methionyl‐ L ‐leucyl‐phenylalanine) are potent mediators for inflammatory reactions. We report functional expression in Xenopus oocytes of human fMLP‐R98 cDNA, without co‐expression of the promiscuous G‐protein subunit, Gα‐16. Stimulation of voltage‐clamped oocytes (−70 mV) with fMLP produced a dose‐depend...

(1) The effects on human homomeric alpha1 glycine receptors of 11 general anaesthetics; four barbiturates, two other intravenous anaesthetics, three volatile anaesthetics and two simple gaseous anaesthetics are described. (2) Pentobarbital and thiopental potentiate the current response to bath applied glycine (50 microM) by 200 and 300%, respective...

The effect of hyperbaric pressure on the inhibitory glycine receptor has been investigated in voltage-clamped Xenopus oocytes microinjected with cRNA encoding the human alpha-1 glycine receptor subunit. Heterologous expression of the human alpha-1 subunit generated functional glycine-gated channels with properties typical of native receptors. Glyci...

This experimental study has revealed damage to red blood cells that is quantitatively related to the acoustic pressure during irradiation with 0.75-MHz continuous-wave ultrasound, using a range of intensities comparable to those employed by ultrasonic physiotherapy equipment (0.25 to 7 W cm-2 spatial average temporal average). Damage to the red blo...

The effect of high pressure on the response to glycine or kainate of voltage-clamped Xenopus oocytes micro-injected with messenger-RNA derived from either rat spinal cord or whole brain, respectively, has been investigated. Current responses were measured at 1 bar (= 10(5) Pa), 50 bar, 100 bar and 150 bar, with PO2 fixed at 1 bar and the balance he...

The idea that general anaesthetics produce unconsciousness, analgesia and amnesia by interfering with communication between neurones is conceptually appealing to both scien- tists and non-scientists. Indeed, there is a long history of considering postsynaptic ligand-gated ion channels (LGICs) as molecular targets for general anaesthetics.59 Advance...

Free radicals, detected as light emissions (sonoluminescence), can be produced in both simple aqueous systems and agar gels by irradiation with 0.75 MHz continuous-wave (CW) ultrasound using acoustic pressures as low as 200 KPa. Although the acoustic pressures necessary for free radical formation in tap water gels (200 KPa), are considerably higher...

The effects of general anesthetics and pressure on receptors from the mammalian central nervous system have been investigated using oocyte expression techniques. Poly A+ mRNA extracted from rat whole brain was injected into mature Xenopus oocytes producing depolarizing responses to the fast excitatory neurotransmitters NMDA and kainate and the inhi...

A range of compounds structurally related to the centrally acting muscle relaxant mephenesin and to the chemical convulsant strychnine were synthesized and tested for their ability to alter the threshold pressures for the onset of high pressure convulsions in mice. The ability of both groups of compounds to alter the threshold pressures for convuls...

A series of benzazole-related, centrally acting muscle relaxants, comprising benzimidazole, chlorzoxazone, and zoxazolamine, were found to give substantial protection against the tremors and convulsions associated with the high pressure neurologic syndrome (HPNS) in the mouse. In this respect they represent a new class of nonanesthetic, anti-HPNS a...

The effects of a variety of structural isomers of the centrally acting muscle relaxant mephenesin on the high pressure neurological syndrome have been investigated. Threshold pressures for the onset of the behavioural signs, tremors and convulsions, were established. The effects of these compounds on the response to pressure were also compared with...

Macroscopically visible gas bubbles can be produced in an agar based gel by irradiation with either continuous or pulsed ultrasound at frequencies from 0.75 to 3.0 MHz. The variation in the number of bubbles formed with frequency, acoustic pressure, pulse length, duty cycle, and temperature closely resembles that seen in vivo. Furthermore, the acou...

Visible size gas bubbles can be produced in an agar based gel when irradiated with either continuous wave (CW) or pulsed ultrasound. It is shown that many aspects of the production of these bubbles can be explained in a qualitative manner by a theoretical model based upon growth of a cavitation nucleus by rectified diffusion. Quantitative predictio...

The hind legs of guinea pigs were exposed to 0.75-MHz ultrasound of different intensities in an attempt to define a threshold for previously observed bubble formation. For continuous-wave ultra- sound, the threshold appears to be around 110 mW cm-', whereas for pulsed ultrasound 2-ms pulse and 2-ms gap the spatial average pulse- averaged intensity...

The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be elimi...

The possibility of stable bubbles being produced during ultrasonic irradiation of a guinea-pig hind limb, has been examined using a pulse echo ultrasonic imaging technique, that can visualise, within a cross-section of the limb, both moving and stationary bubbles of diameters down to 10 mu m (Beck et al. 1978). The observations reported clearly sho...

1. Bubble formation in the hind limb of anaesthetized guinea-pigs, after decompression from two different saturation exposures to air, 0.69 and 0.83 MPa gauge, has been studied using an ultrasonic pulse--echo imaging technique. 2. A qualitative analysis of the bubble formation, observed over a 30 min period after decompression, showed that profuse,...

The effects of high pressure on the whole brain concentrations of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), and noradrenaline (NA) were determined in the mouse. Application of high pressure (over 100atm) elevated the brain 5-HIAA concentrations but had little or no influence on the concentrations of 5-HT, DA, o...

An high-resolution pulse echo ultrasonic imaging system has been developed to study decompression-induced gas bubbles. It was considered necessary that the system be capable of detecting gas bubbles with a diameter of 10 micrometer and up and be able to monitor the growth of these bubbles. In addition the system needed to be capable of distinguishi...

1. Decompression from exposures to raised ambient pressure of sulphur hexafluoride, carbon tetrafluoride, hexafluoro-ethane and nitrous oxide results in the formation of dense foam and pulmonary oedema. 2. The degree of pulmonary oedema produced is dependent on the exposure pressure, although the exposure time required is short in comparison to tis...

AMATEUR diving and industrial demands have changed decompression sickness from being a specialised problem to becoming a health risk for many thousands of people. Rising medical standards and the recognition of bone damage1 have resulted in increasingly stringent diving regulations, but the devising of suitable decompression schedules is still larg...

The anaesthetic potencies of binary mixtures of the gases argon (Ar), nitrous oxide (N2O) and sulphur hexafluoride (SF6) have been measured using mice. The mixtures SF6-N2O and N2O-Ar showed additive behaviour, whereas the constituents of the mixture SF6-Ar were non-additive, having a smaller total potency than expected. Further experiments on this...