Publications by authors named "Paul Francis"

Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)(A) receptor channel (apparent IC50 = 0.

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Background: Serotonin 1A receptors (5-HT(1A)) have not been studied in dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD) patients with depression.

Aim: To examine 5-HT(1A) in DLB and PDD postmortem in relation to depression.

Methods: [(3)H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT(1A) was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls.

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Three recently reported chemiluminescence methods (based on reactions with alkaline luminol and hexacyanoferrate(III); acidic cerium(IV) and rhodamine B; and acidic permanganate with polyphosphates) for the determination of synephrine were re-evaluated in terms of their selectivity towards this analyte in comparison to other phenolic compounds. A fourth reagent system, acidic soluble manganese(IV) and formaldehyde, was also examined. Each set of reagents was sensitive towards synephrine (limits of detection were 3 x 10(-9), 5 x 10(-8), 1 x 10(-8) and 1 x 10(-8) mol/L, respectively) but also responded with numerous other phenolic compounds, including some that are present in citrus fruit extracts, dietary supplements and/or biological fluids.

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Objective: Our aim was to determine the safety of BAL in young children <6 years with CF.

Methods: As part of a multi-center study of BAL-directed therapy, children with CF < 6 years had one or more BALs between September 1999 and December 2005. Adverse events were recorded intraoperatively and for 24 hr thereafter.

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A review with 98 references. The determination of the opium poppy (Papaver somniferum) alkaloids and their semi-synthetic derivatives has important applications in industrial process monitoring, clinical analysis and forensic science. Liquid-phase chemiluminescence reagents such as tris(2,2'-bipyridyl)ruthenium(II) and acidic potassium permanganate exhibit remarkable sensitivity and complementary selectivity for many P.

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Although potassium permanganate [Mn(VII)] has been used extensively as a chemiluminescence reagent for many decades, other manganese-based oxidants have only recently been explored for this purpose. There is strong evidence to suggest that, like permanganate, manganese(III) and manganese(IV) oxidants react with many molecules to produce an excited manganese(II) species that emits light. However, these reagents differ markedly in terms of selectivity, and possess characteristics that provide new avenues for detection, such as the immobilisation of solid manganese dioxide, the production of 'soluble' manganese(IV) nanoparticles, and the electrochemical generation of manganese(III).

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A sequential injection analysis procedure with dual-reagent chemiluminescence detection was applied to the screening of street drug seizure samples for the presence of heroin. The chemiluminescence reagents (acidic potassium permanganate and tris(2,2'-bipyridine)ruthenium(III)) were aspirated from either side of a sample aliquot that was sufficiently large to prevent interdispersion of the reagent zones, and therefore two different chemical reactions could be performed simultaneously at either end of the sample zone. The presence of heroin in seizure samples was indicated by a strong response with the tris(2,2'-bipyridine)ruthenium(III) reagent and confirmed by a significant increase in the response with the permanganate reagent when the sample was treated with sodium hydroxide to hydrolyse the heroin to morphine.

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We studied the hypothesis that disturbances in 5-HT_{6} receptor function in the temporal cortex may contribute to clinical symptoms of Alzheimer's disease (AD). 5-HT_{6} density and 5-HT levels were significantly decreased in a cohort of AD patients prospectively assessed for cognitive/behavioral symptoms. cAMP formation after stimulation with the selective 5-HT_{6} receptor agonist E-6801 was significantly lower (p<0.

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The uridine nucleotide-activated P2Y2, P2Y4 and P2Y6 receptors are widely expressed in the brain and are involved in many CNS processes, including those which malfunction in Alzheimer's disease (AD). However, the status of these receptors in the AD neocortex, as well as their putative roles in the pathogenesis of neuritic plaques and neurofibrillary tangles, remain unclear. In this study, we used immunoblotting to measure P2Y2, P2Y4 and P2Y6 receptors in two regions of the postmortem neocortex of neuropathologically assessed AD patients and aged controls.

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Alzheimer's disease (AD) is a common neurodegenerative disorder, but the initiating molecular processes contributing to neuronal death are not well understood. AD is associated with elevated soluble and aggregated forms of amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing evidence for a detrimental role of iron in the pathogenic process.

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The glutamatergic system has long been recognised for its role in learning and memory and recent studies indicate an early loss of glutamatergic synapses in Alzheimer's disease (AD). Efforts to produce drugs which address changes in the glutamatergic system in AD are well advanced (e.g.

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Vascular dementia (VaD) accounts for about 20% of all dementias, and vascular risk is a key factor in more than 40% of people with Alzheimer's disease (AD). Little is known about inflammatory processes in the brains of these individuals. We have examined inflammatory mediators (interleukin (IL)-1beta, IL-1alpha, IL-6 and tumour necrosis factor alpha) and chemokines (macrophage inflammatory protein 1, monocyte chemo-attractant protein (MCP)-1 and granulocyte macrophage colony-stimulating factor) in brain homogenates from grey and white matter of the frontal cortex (Brodmann area 9) from patients with VaD (n = 11), those with concurrent VaD and AD (mixed dementia; n = 8) and from age-matched controls (n = 13) using ELISA assays.

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A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically-validated essential oil derived from Melissa officinalis (MO), which has shown clinical benefit in treating agitation. MO inhibited binding of [35S] t-butylbicyclophosphorothionate (TBPS) to the rat forebrain gamma-aminobutyric acid (GABA)(A) receptor channel (apparent IC50 0.040+/-0.

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We present a fully automated DNA purification module comprised of a micro-fabricated chip and sequential injection analysis system that is designed for use within autonomous instruments that continuously monitor the environment for the presence of biological threat agents. The chip has an elliptical flow channel containing a bed (3.5 x 3.

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It is now 30 years since the beginning of intensive efforts to understand the neurotransmitter biochemistry of dementia as exemplified by Alzheimer's disease and such studies have led to the development of rational treatment strategies, which are continuing to benefit patients. However, as studies became more sophisticated and clinicians rediscovered an interest in dementia, because of the potential for symptomatic treatment, it has become clear that there are several different neurodegenerative conditions that gives rise to dementia syndromes and that each has distinct neurochemical pathology. This has important treatment implications since what works for one may not work for another or at the extreme, may make matters worse.

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A direct comparison of the laser-induced photoluminescence of manganese(ii) with the chemiluminescence from the reaction between acidic potassium permanganate and sodium borohydride was used to confirm that the characteristic red emission from this widely used chemiluminescence reagent emanates from an electronically excited manganese(ii) species.

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A critical and comprehensive review of acidic potassium permanganate chemiluminescence is presented. This includes discussion on reaction conditions, the influence of enhancers such as polyphosphates, formaldehyde and sulfite, the relationship between analyte structure and chemiluminescence intensity, and the application of this chemistry to determine a wide variety of compounds, such as pharmaceuticals, biomolecules, antioxidants, illicit drugs, pesticides and pollutants. Previous proposals for the nature of the emitting species are re-evaluated in light of recent evidence.

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We have combined the generation of solvent gradients using milliGAT pumps, chromatographic separations with monolithic columns and chemiluminescence detection in an instrument manifold that approaches the automation and separation efficiency of HPLC, whilst maintaining the positive attributes of flow injection analysis (FIA), such as manifold versatility, speed of analysis and portability. As preliminary demonstrations of this hybrid FIA/HPLC system, we have determined six opiate alkaloids (morphine, pseudomorphine, codeine, oripavine, ethylmorphine and thebaine) and four biogenic amines (vanilmandelic acid, serotonin, 5-hydroxyindole-3-acetic acid and homovanillic acid) in human urine, using tris(2,2'-bipyridyl)ruthenium(III) and acidic potassium permanganate chemiluminescence detection.

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Background: Airway inflammation in cystic fibrosis (CF) is exaggerated and characterized by neutrophil-mediated tissue destruction, but its genesis and mechanisms remain poorly understood. To further define the pulmonary inflammatory response, we conducted a proteome-based screen of bronchoalveolar lavage fluid (BALF) collected from young children with and without CF experiencing endobronchial infection.

Methods: We collected BALF samples from 45 children younger than 5 years and grouped them according to the presence of respiratory pathogens: > or = 1 x 10(5) colony-forming units (CFU)/mL BALF (18 and 12 samples with and without CF, respectively) and <1 x 10(5) CFU/mL (23 and 15 samples).

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We have combined high-performance liquid chromatography (HPLC) separations using a monolithic column with acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection in a rapid and highly sensitive method to monitor the process of extracting opiate alkaloids from Papaver somniferum. Due to the high flow rates allowed with the monolithic column and the inherent selectivity of the chemiluminescence reactions, the four predominant alkaloids--morphine, codeine, oripavine and thebaine--were determined in less than 2 min. The results obtained with numerous process samples compared favourable with those of the standard HPLC methodology.

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A high-performance liquid chromatography (HPLC) method for the determination of urea that incorporates automated derivatisation with xanthydrol (9H-xanthen-9-ol) is described. Unlike the classic xanthydrol approach for the determination of urea, which involves the precipitation of dixanthylurea (N,N'-di-9H-xanthen-9-ylurea), the derivatisation procedure employed in this method produces N-9H-xanthen-9-ylurea, which remains in solution and can be quantified using fluorescence detection (lambda(ex)=213 nm; lambda(em)=308 nm) after chromatographic separation from interferences. The limit of detection for urea was 5 x 10(-8) M (0.

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