• Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract

      Ajaiyeoba, E.O.; Ogbole, O.O.; Abiodun, O.O.; Ashidi, J.S.; Houghton, P.J.; Wright, Colin W. (2013-02)
      Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μg/mL (7.4 μM) and could be a lead for anti-malarial drug discovery.
    • Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates.

      Schallreuter, Karin U.; Gibbons, Nick C.; Elwary, Souna M.A.; Parkin, Susan M.; Wood, John M. (2007)
      The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 × 10-3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H2O2-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m2 surface area with its calcium gradient in the 10¿3 M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue
    • Calculation and Measurement of Terahertz Active Normal Modes in Crystalline PETN

      Burnett, A.; Kendrick, John; Cunningham, J.E.; Hargreaves, Michael D.; Munshi, Tasnim; Edwards, Howell G.M.; Linfield, E.H.; Davies, G.A. (2010)
      The terahertz frequency spectrum of pentaerythritol tetranitrate (PETN) is calculated using Discover[1] with the COMPASS[2] force field, CASTEP[3] and PWscf.[4] The calculations are compared to each other and to terahertz spectra (0.3-3 THz) of crystalline PETN recorded at 4 K. A number of analysis methods are used to characterise the calculated normal modes.
    • Calculation of electrophoretic mobility in mixed solvent buffers in capillary zone electrophoresis using a mixture response surface method.

      Jouyban, A.; Grosse, S.C.; Coleman, M.W.; Chan, H.K.; Kenndler, E.; Clark, Brian J. (2009-10-27)
      The electrophoretic mobilities of three beta-blocker drug practolol, timolol and propranolol, have been measured in electrolyte systems with mixed binary and ternary water-methanol-ethanol solvents with acetic acid/sodium acetate as buffer using capillary electrophoresis. The highest mobilities for the analytes studied have been observed in pure aqueous. the lowest values in ethanolic buffers The measured electrophoretic mobilities have been used to evaluate the accuracy of a mathematical model based on a mixture response surface method that expresses the mobility as a function of the solvent composition. Mean percentage error (MPE) has been computed considering experimental and calculated mobilities as an accuracy criterion. The obtained MPE for practolol, timolol and propranolol in the binary mixtures are between 0.9 and 2.6%, in the ternary water-methanol-ethanol solvent system the MPE was about 2.7%. The MPE values resulting from the proposed equation lie within the experimental relative standard deviation values and can he considered as an acceptable error.
    • Calculation of the melting point of NaCl by molecular simulation.

      Anwar, Jamshed; Frenkel, D.; Noro, M.G. (2009-11-25)
      We report a numerical calculation of the melting point of NaCl. The solid-liquid transition was located by determining the point where the chemical potentials of the solid and liquid phases intersect. To compute these chemical potentials, we made use of free energy calculations. For the solid phase the free energy was determined by thermodynamic integration from the Einstein crystal. For the liquid phase two distinct approaches were employed: one based on particle insertion and growth using the Kirkwood coupling parameter, and the other involving thermodynamic integration of the NaCl liquid to a Lennard-Jones fluid. The latter approach was found to be significantly more accurate. The coexistence point at 1074 K was characterized by a pressure of -30+/-40 MPa and a chemical potential of -97.9+/-0.2kßT. This result is remarkably good as the error bounds on the pressure enclose the expected coexistence pressure of about 0.1 MPa (ambient). Using the Clausius-Clapyron relation, we estimate that dP/dT~3 MPa/K. This yields a melting point of 1064+/-14 K at ambient pressure, which encompasses the quoted range for the experimental melting point (1072.45-1074.4 K). The good agreement with the experimental melting-point data provides additional evidence that the Tosi-Fumi model for NaCl is quite accurate. Our study illustrates that the melting point of an ionic system can be calculated accurately by employing a judicious combination of free energy techniques. The techniques used in this work can be directly extended to more complex, charged systems.
    • The Caledonian face test: A new test of face discrimination

      Logan, Andrew J.; Wilkinson, F.; Wilson, H.R.; Gordon, G.E.; Loffler, G. (2016-02)
      This study aimed to develop a clinical test of face perception which is applicable to a wide range of patients and can capture normal variability. The Caledonian face test utilises synthetic faces which combine simplicity with sufficient realism to permit individual identification. Face discrimination thresholds (i.e. minimum difference between faces required for accurate discrimination) were determined in an "odd-one-out" task. The difference between faces was controlled by an adaptive QUEST procedure. A broad range of face discrimination sensitivity was determined from a group (N=52) of young adults (mean 5.75%; SD 1.18; range 3.33-8.84%). The test is fast (3-4min), repeatable (test-re-test r2=0.795) and demonstrates a significant inversion effect. The potential to identify impairments of face discrimination was evaluated by testing LM who reported a lifelong difficulty with face perception. While LM's impairment for two established face tests was close to the criterion for significance (Z-scores of -2.20 and -2.27) for the Caledonian face test, her Z-score was -7.26, implying a more than threefold higher sensitivity. The new face test provides a quantifiable and repeatable assessment of face discrimination ability. The enhanced sensitivity suggests that the Caledonian face test may be capable of detecting more subtle impairments of face perception than available tests.
    • A calf for all seasons? The potential of stable isotope analysis to investigate prehistoric husbandry practices

      Towers, Jacqueline R.; Jay, Mandy; Mainland, Ingrid L.; Nehlich, O.; Montgomery, Janet (2011-08)
      The Early Bronze Age barrows at Irthlingborough and Gayhurst in central England are notable for the large number of cattle (Bos taurus) remains associated with their human Beaker burials. Previous work using strontium isotope analysis has indicated that most of the cattle analysed, and one aurochs (Bos primigenius), were of local origin (Towers et al. 2010). In this study, stable isotope analysis of enamel and bone was carried out to investigate whether the mature cattle had experienced similar husbandry practices, climate and environment. Bulk carbon, nitrogen and sulphur isotope analysis of collagen suggested most were consuming similar sources of plant protein from environments probably local to the sites and this was supported by high resolution intra-enamel carbon isotope profiles. Oxygen isotope profiles indicated the aurochs and most of the cattle experienced similar climatic regimes: the only exception being an animal with a non-local strontium isotope ratio. However, a comparison of seasonality profiles of the local animals using estimated tooth formation times showed that there was no consistency in season of birth: the animals appeared to have been born throughout the year. Cattle can breed throughout the year but it requires considerable human effort and intervention to successfully overwinter young stock; it is therefore unlikely to have been carried out without good reason and benefit if winters were harsh. One reason is to ensure a continuous supply of milk. Measuring oxygen isotope profiles to identify year-round calving may thus be a potential indicator of dairying economies.
    • Calving seasonality at Pool, Orkney during the first millennium AD: an investigation using intra-tooth isotope ratio analysis of cattle molar enamel

      Towers, Jacqueline R.; Mainland, Ingrid L.; Montgomery, Janet; Bond, Julie M. (2017)
      The identification of dairying is essential if we are to understand economies of the past, particularly in northwest Europe, where a high degree of lactose tolerance suggests that fresh milk has long been a significant food product. This paper explores a possible link between economic focus and seasonality of calving. Although cattle (Bos taurus) can breed throughout the year, animals living in temperate regions with minimal or no human management tend to breed seasonally, their breeding behaviour being strongly influenced by the availability of food. In order to achieve a year-round supply of fresh milk in the past, it is likely that multiple-season calving was necessary, which would have required additional husbandry effort. Alternatively, for meat-focussed economies or those based on storable dairy products, a strategy of single-season calving in spring may have been favoured to maximise the utilization of spring and summer vegetation. Cattle birth seasonality is investigated through isotope ratio analysis (δ18O, δ13C) of tooth enamel. Results for cattle from Pool, Orkney dating to the latter part of the first millennium A.D suggest that calving occurred during at least three seasons implying that the continuous provision of fresh milk was of economic importance.
    • Can ancient texts assist in the development of herbal treatments for malaria?

      Wright, Colin W.; Linley, Peter A.; Brun, R.; Wittlin, S.; Hsu, E. (2014)
    • Can contrast-response functions indicate visual processing levels?

      Breitmeyer, B.G.; Tripathy, Srimant P.; Brown, J.M. (2018-03-01)
      Many visual effects are believed to be processed at several functional and anatomical levels of cortical processing. Determining if and how the levels contribute differentially to these effects is a leading problem in visual perception and visual neuroscience. We review and analyze a combination of extant psychophysical findings in the context of neurophysiological and brain-imaging results. Specifically using findings relating to visual illusions, crowding, and masking as exemplary cases, we develop a theoretical rationale for showing how relative levels of cortical processing contributing to these effects can already be deduced from the psychophysically determined functions relating respectively the illusory, crowding and masking strengths to the contrast of the illusion inducers, of the flankers producing the crowding, and of the mask. The wider implications of this rationale show how it can help to settle or clarify theoretical and interpretive inconsistencies and how it can further psychophysical, brain-recording and brain-imaging research geared to explore the relative functional and cortical levels at which conscious and unconscious processing of visual information occur. Our approach also allows us to make some specific predictions for future studies, whose results will provide empirical tests of its validity.
    • Can data in optometric practice be used to provide an evidence base for ophthalmic public health?

      Slade, S.V.; Davey, Christopher J.; Shickle, D. (2016-07)
      Purpose: The purpose of this paper is to investigate the potential of using primary care optometry data to support ophthalmic public health, research and policy making. Methods: Suppliers of optometric electronic patient record systems (EPRs) were interviewed to gather information about the data present in commercial software programmes and the feasibility of data extraction. Researchers were presented with a list of metrics that might be included in an optometric practice dataset via a survey circulated by email to 102 researchers known to have an interest in eye health. Respondents rated the importance of each metric for research. A further survey presented the list of metrics to 2000 randomly selected members of the College of Optometrists. The optometrists were asked to specify how likely they were to enter information about each metric in a routine sight test consultation. They were also asked if data were entered as free text, menus or a combination of these. Results: Current EPRs allowed the input of data relating to the metrics of interest. Most data entry was free text. There was a good match between high priority metrics for research and those commonly recorded in optometric practice. Conclusions: Although there were plenty of electronic data in optometric practice, this was highly variable and often not in an easily analysed format. To facilitate analysis of the evidence for public health purposes a UK based minimum dataset containing standardised clinical information is recommended. Further research would be required to develop suitable coding for the individual metrics included. The dataset would need to capture information from all sectors of the population to ensure effective planning of any future interventions.
    • Can green synthesized propolis loaded silver nanoparticulate gel enhance wound healing caused by burns?

      Patil, S.S.; Desai, N.; Mahadik, K.R.; Paradkar, Anant R. (2015)
      Nanotechnology can offer new opportunities in the fight against infection. The aim of current work was to investigate an eco-friendly method for synthesis of silver nanoparticles (AgNP) which have the ability to load lipophilic compounds onto their surface. Pharmaceutically acceptable hydrophilic lipid (Gelucire® 50/13) has been used as a reducing agent for in situ reduction of silver nitrate so as to obtain silver nanoparticles. Propolis is used as model molecule for loading onto surface of AgNP owing to its well reported broad range of pharmacological activities including anti-inflammatory, antioxidant and antimicrobial activity. Propolis loaded silver nanoparticles (PLSN) were prepared and characterized for silver content, surface plasmon resonance, particle size, XRD, FTIR, TEM, antibacterial activity and burn wound healing in wistar rats. Propolis constituents were successfully loaded onto surface of AgNP using the proposed conceptual method. The formation of PLSN having size 24.3 ± 2.5 nm was confirmed using surface plasmon resonance, FTIR, XRD and TEM. The combination of propolis with AgNP significantly reduced minimum inhibitory concentration of AgNP alone when tested against Staphylococcus aureus. PLSN gel showed comparable burn wound healing in wistar rats when tested against marketed silver sulfadiazine gel. The use of Gelucire® as solubilizing agent for lipophillic drugs was effectively utilized for loading lipophillic constituents of propolis onto the AgNP. This potentially provides an effective method for the green synthesis of AgNP which can be used to load lipophillic molecules onto their surface whenever such combination is required.
    • Can optical recordings of membrane potential be used to screen for drug-induced action potential prolongation in single cardiac myocytes?

      Hardy, Matthew E.; Lawrence, C.L.; Standen, N.B.; Rodrigo, G.C. (2006)
      Introduction: Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. Materials and methods: We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. Results: Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6 ± 13.5 vs. 296.2 ± 16.2ms; p< 0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91 ± 46 vs. 81 ± 20 nM). Discussion: These data show that the optical AP recorded ratiometrically using di-8- ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than conventional electrophysiological techniques and, when coupled to ventricular myocytes, decreases animal usage and facilitates higher throughput assays.
    • Can plant-derived phytochemicals provide symptom relief for hair loss? A critical review

      Daniels, G.; Akram, S.; Westgate, Gillian E.; Tamburic, S. (2019-08)
      It is known that hair growth disorders and hair loss can cause personal distress and affect well‐being. Whilst clinical conditions remain a target for medical research, current research on hair follicle biology and hair growth control mechanisms also provides opportunities for a range of non‐medical and cosmetic interventions that have a modulating effect on the scalp and follicle function. Furthermore, an improvement of the hair fibre characteristics (cuticle structure, cortex size and integrity) could add to the overall positive visual effect of the hair array. Since phytochemicals are a popular choice because of their traditional appeal, this review provides a critical evaluation of the available evidence of their activity for hair benefit, excluding data obtained from animal tests, and offers recommendations on improving study validity and the robustness of data collection in pre‐clinical and clinical studies.
    • Can We Create a Circular Pharmaceutical Supply Chain (CPSC) to Reduce Medicines Waste?

      Alshemari, Abdullah; Breen, Liz; Quinn, Gemma; Sivarajah, Uthayasankar (2020-11-18)
      The increase in pharmaceutical waste medicines is a global phenomenon and financial burden. The Circular Economy, as a philosophy within the pharmaceutical supply chain, aims to promote waste reduction, maximise medicines value, and enable sustainability within this supply chain (increasing circularity). Circularity strategies for pharmaceuticals are not currently implemented in many countries, due to quality and safety barriers. The aim of this study was to determine whether the application of circular economy principles can minimise pharmaceutical waste and support sustainability in the pharmaceutical supply chain; Methods: a detailed narrative literature review was conducted in order to examine pharmaceutical waste creation, management, disposal, and the application of circular economy principles; Results: the literature scrutinised revealed that pharmaceutical waste is created by multiple routes, each of which need to be addressed by pharmacists and healthcare bodies through the Circular Economy 9R principles. These principles act as a binding mechanism for disparate waste management initiatives. Medicines, or elements of a pharmaceutical product, can be better managed to reduce waste, cost, and reduce negative environmental impacts through unsafe disposal. the study findings outline a Circular Pharmaceutical Supply Chain and suggests that it should be considered and tested as a sustainable supply chain proposition.
    • Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms

      Mancini, S.J.; Boyd, D.; Katwan, O.J.; Strembitska, A.; Almabrouk, T.A.; Kennedy, S.; Palmer, Timothy M.; Salt, I.P. (2018-03)
      Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells. Incubation with clinically-relevant concentrations of canagliflozin, but not empagliflozin or dapagliflozin activated AMPK and inhibited IL-1β-stimulated adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated by expression of dominant-negative AMPK and was mimicked by the direct AMPK activator, A769662. Stimulation of cells with either canagliflozin or A769662 had no effect on IL-1β-stimulated cell surface levels of adhesion molecules or nuclear factor-κB signalling. Despite these identical effects of canagliflozin and A769662, IL-1β-stimulated IL-6/MCP-1 mRNA was inhibited by canagliflozin, but not A769662, whereas IL-1β-stimulated c-jun N-terminal kinase phosphorylation was inhibited by A769662, but not canagliflozin. These data indicate that clinically-relevant canagliflozin concentrations directly inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK-dependent and -independent mechanisms without affecting early IL-1β signalling.
    • Cancer patients’ views on community pharmacy pain medicines consultations in advanced cancer

      Edwards, Zoe; Blenkinsopp, Alison; Ziegler, Lucy; Bennett, M. (2016-04)
      Every year in England and Wales, 105,000 people sufferfrom uncontrolled cancer pain and are rarely offered community pharmacy medicine consultations (e.g. Medicines Use Reviews -MURs)[1]. Our aim was to examine how patients with cancer pain deal with their pain medication and to investigate their experiences of and attitudes towards community pharmacy.
    • Candidate Treponema pallidum biomarkers uncovered in urine from individuals with syphilis using mass spectrometry

      Osbak, K.K.; Van Raemdonck, G.A.; Dom, M.; Cameron, C.E.; Meehan, Conor J.; Deforce, D.; Van Ostade, X.; Kenyon, C.R.; Dhaenens, M. (2018-10)
      Aim: A diagnostic test that could detect Treponema pallidum antigens in urine would facilitate the prompt diagnosis of syphilis. Materials & methods: Urine from 54 individuals with various clinical stages of syphilis and 6 controls were pooled according to disease stage and interrogated with complementary mass spectrometry techniques to uncover potential syphilis biomarkers. Results & conclusion: In total, 26 unique peptides were uncovered corresponding to four unique T. pallidum proteins that have low genetic sequence similarity to other prokaryotes and human proteins. This is the first account of direct T. pallidum protein detection in human clinical samples using mass spectrometry. The implications of these findings for future diagnostic test development is discussed. Data are available via ProteomeXchange with identifier PXD009707.
    • The Canny edge detector revisited

      McIlhagga, William H. (16/10/2010)
      Canny (IEEE Trans. Pattern Anal. Image Proc. 8(6):679-698, 1986) suggested that an optimal edge detector should maximize both signal-to-noise ratio and localization, and he derived mathematical expressions for these criteria. Based on these criteria, he claimed that the optimal step edge detector was similar to a derivative of a gaussian. However, Canny's work suffers from two problems. First, his derivation of localization criterion is incorrect. Here we provide a more accurate localization criterion and derive the optimal detector from it. Second, and more seriously, the Canny criteria yield an infinitely wide optimal edge detector. The width of the optimal detector can however be limited by considering the effect of the neighbouring edges in the image. If we do so, we find that the optimal step edge detector, according to the Canny criteria, is the derivative of an ISEF filter, proposed by Shen and Castan (Graph. Models Image Proc. 54:112-133, 1992). In addition, if we also consider detecting blurred (or non-sharp) gaussian edges of different widths, we find that the optimal blurred-edge detector is the above optimal step edge detector convolved with a gaussian. This implies that edge detection must be performed at multiple scales to cover all the blur widths in the image. We derive a simple scale selection procedure for edge detection, and demonstrate it in one and two dimensions.
    • Capabilities of potential vision test measurements - clinical evaluation in the presence of cataract or macular disease.

      Vianya-Estopa, Marta; Douthwaite, William A.; Noble, B.A.; Elliott, David B. (2007)
      Purpose To determine the usefulness of a battery of potential vision tests (PVTs) including potential acuity meter (PAM), laser interferometer (LI), critical flicker/fusion frequency (CFF), superilluminated pinhole at distance (SPHd) and near (SPHn), and optimal reading speed (ORS) by their independence of the effects of cataracts and sensitivity to macular disease (MD). Setting Department of Optometry, University of Bradford, Bradford and Leeds General Infirmary, Leeds, United Kingdom. Methods Potential vision test measurements were determined in 76 patients with age-related cataract and no other eye disease, 52 patients with MD and clear ocular media, and 28 patients with normal, healthy eyes. Results Potential vision tests were independent of the degrading effects of cataract up to a visual acuity (VA) level of 20/200 or worse (CFF), 20/125 (ORS and SPH), and 20/40 (PAM and LI). A high degree of association was found between PVT scores and distance VA in the MD group for SPHd (r2 = 0.93), SPHn (r2 = 0.89), and PAM (r2 = 0.71). A moderate correlation was found for LI (r2 = 0.55), CFF (r2 = 0.50), and ORS (r2 = 0.45). Conclusions Potential acuity meter and LI showed very limited independence to moderate/dense cataracts and inaccurate predictions in patients with MD. Superilluminated pinhole was relatively unaffected by moderate/dense cataract and yet provided accurate predictions in the presence of MD and clear ocular media. Critical flicker/fusion frequency showed the greatest ability to bypass cataracts, although its ability to predict VA in patients with early MD was limited. The ORS was relatively unaffected by moderate/dense cataract, but its poor ability to predict VA in MD may limit its clinical suitability as a PVT.