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The Livestock Burdent of Parasitism Database: A Strategic Management Tool
Simon BROWN,David C. SIMCOCK
Leonardo Electronic Journal of Practices and Technologies , 2010,
Abstract: The parasite burden of livestock places an enormous burden on both the animals and farmer. Parasite control usually involves the use of anthelmintics to which the parasites are rapidly developing resistance. To prolong the usefulness of the current generation of anthelmintics it is prudent to monitor their use and effectiveness, and provide reliable advice to farmers and veterinarians in order to minimise their use. We describe the prototype of the Livestock Burden of Parasitism database that is based on a Java interface to R which generates the web pages and graphics needed to respond to the requests of a user. The database is accessible at various levels according to the needs of the user and allows the input and checking of new data as well as the output of appropriate summaries of existing data. The database provides a tool for the management of anthelmintic use, the identification of successful treatment strategies and the provision of advice.
Confidence Bands for Rational Rate Equations
Simon Brown,David C. Simcock
International Journal of Emerging Sciences , 2013,
Abstract: The standard Michaelis-Menten expression for the rate of an enzyme-catalysed reaction (v) can be extended using the ratio of two polynomials in the substrate concentration (s). Such rational functions are nonlinear and their behaviour can vary considerably. Comparisons of two such functions requires more than a simple consideration of a particular coefficient, especially given the coefficients do not necessarily have any mechanistic significance. A second issue is the identification of particular coefficients that contribute significantly to the overall error of the estimate of v at a given s. As the number of coefficients rises this becomes increasingly difficult. To address the first of these issues we provide a general expression for the estimated confidence band of an arbitrary rational function of this type. We employ sensitivity analysis to address the second issue and provide general expressions for the coefficient elasticities. We apply these in the analysis of the kinetics of chymotrypsin and muscle lactate dehydrogenase.
Half a century of the chemiosmotic hypothesis and the practice of science
Simon Brown,David C. Simcock
Orbital : the Electronic Journal of Chemistry , 2011,
Abstract: The first published outline of the chemiosmotic hypothesis of biological energy transduction was published fifty years ago. It took many years for the ideas to be accepted despite their elegance. We outline the basis and history of the hypothesis and consider what can be learnt from it about the development of new ideas in science and what is required to persuade the community of a new idea given a pre-existing model.
What Happens When the Wrong Equation is Fitted to Data?
Simon Brown,Noorzaid Muhamad,Kevin C Pedley,David C Simcock
International Journal of Emerging Sciences , 2012,
Abstract: A common variant of the Michaelis-Menten model of enzyme kinetics involves inhibition by excess substrate. This phenomenon is known as substrate inhibition and the mathematical description of it requires an inhibition constant (Ki) as well as the usual kinetic parameters (Km and Vmax). Fitting the 3-parameter substrate inhibition expression to data that might reasonably be described by the 2-parameter Michaelis-Menten model yields biased estimates of Km and Vmax. Numerical simulations demonstrate that the extent of the bias is related to the magnitude of the estimated Ki. The quality of the data is particularly important in determining the size of Ki and, therefore, in the bias of the other parameters. Consideration of the residuals, statistical justification of the inclusion of extra parameters and reporting of the estimated values should be matters of routine. The estimates of Km and Vmax obtained from a three-parameter substrate inhibition model can only be compared with the corresponding estimates from the two-parameter Michaelis-Menten model with caution.
A Simple Confidence Band for the Michaelis-Menten Equation
Simon Brown,Noorzaid Muhamad,Kevin C. Pedley,David C. Simcock
International Journal of Emerging Sciences , 2012,
Abstract: Analysis of enzyme kinetic data requires more than just comparisons of Kms and Vmaxs using the corresponding error estimates of the parameters. This approach is often employed, but it can prompt contradictory and misleading inferences that might be avoided using a confidence band. We derive expressions for the confidence band for the Michaelis-Menten rate equation that rely on estimates and variances of Km and Vmax. These can be expressed in terms of the substrate concentration or the rate of reaction. While these equations are simple, they are nonlinear, which reinforces the need to consider both parameters simultaneously. The equations show that the amplitude of the confidence interval ( ) passes through a maximum if the variance of the Km is sufficently large compared with the variance of Vmax. We illustrate the value of the expressions by applying them to comparisons of the kinetics of enzymes involved in nitrogen metabolism in parasites. These examples confirm that (i) the variance of the estimate of the Km has a particularly significant effect on and (ii) comparisons among Kms and among Vmaxs are not necessarily sufficient to determine the significance of differences in activity.
The Kinetics of Enzyme Mixtures
Simon Brown, Noorzaid Muhamad, Kevin C Pedley, David C Simcock
Molecular Biology Research Communications , 2014,
Abstract: Even purified enzyme preparations are often heterogeneous. For example, preparations of aspartate aminotransferase or cytochrome oxidase can consist of several different forms of the enzyme. For this reason we consider how different the kinetics of the reactions catalysed by a mixture of forms of an enzyme must be to provide some indication of the characteristics of the species present. Based on the standard Michaelis-Menten model, we show that if the Michaelis constants (Km) of two isoforms differ by a factor of at least 20 the steady-state kinetics can be used to characterise the mixture. However, even if heterogeneity is reflected in the kinetic data, the proportions of the different forms of the enzyme cannot be estimated from the kinetic data alone. Consequently, the heterogeneity of enzyme preparations is rarely reflected in measurements of their steady-state kinetics unless the species present have significantly different kinetic properties. This has two implications: (1) it is difficult, but not impossible, to detect molecular heterogeneity using kinetic data and (2) even when it is possible, a considerable quantity of high quality data is required.
Complete clinical and pathological response to preoperative short course radiotherapy in T 2 rectal cancer
Selvasekar C,Obeidat S,Simcock P,Khan A
Indian Journal of Cancer , 2009,
Abstract:
The Acute Physiological Effects of the Vaso-Active Drug, L-NNA, a Nitric Oxide Synthase Inhibitor, on Renal and Tumour Perfusion in Human Subjects  [PDF]
Kent Yip, Vicky Goh, Jane Gregory, Ian Simcock, J. James Stirling, N. Jane Taylor, Robert Kozarski, Andrew Mitchell, Sam Bosopem, Gavin Halbert, Roberto Alonzi, David Miles, Peter Hoskin
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.51006
Abstract:

Purpose: To assess the baseline variation in global renal and tumour blood flow, blood volume and extraction fraction, and changes in these parameters related to the acute physiological effects of a single dose of a non selective inhibitor of nitric oxide synthase, L-NNA. Materials & Methods: Ethical approval and informed consent were obtained for this Phase I clinical study. Patients with advanced solid tumours refractory to conventional therapy were recruited and given L-NNA intravenously at two different dose levels. Volumetric perfusion CT scans were carried out at 1, 24, 48 & 72 hours post L-NNA. Blood pressures were taken at regular interval for 6 hours after LNNA. Results: L-NNA was well tolerated by the four patients who received it. Blood flow (BF) and blood volume (BV) in both tumour and kidney were reduced post L-NNA administration (renal BF—20%; renal BV—19.7%; tumour BF—16.9%; tumour BV—18.6%), though the effect was more sustained in tumour vasculature. A negative correlation was found between the change in systemic blood pressure and vascular supply to the tumour within 1 hour following L-NNA (p < 0.0001). Differences in response to L-NNA by separate target lesions in the same patient were observed. Conclusion: The differential effect of L-NNA on tumour and renal blood flow, and the absence of any significant toxicity in this small cohort of patients permit further dose escalation of L-NNA in future early phase trials. The predictive value of blood pressure change in relation to the acute effect of L-NNA on tumour vasculature deserves further evaluation.

A Randomized Steady-State Bioavailability Study of Synthetic versus Natural (Kiwifruit-Derived) Vitamin C
Anitra C. Carr,Stephanie M. Bozonet,Juliet M. Pullar,Jeremy W. Simcock,Margreet C. M. Vissers
Nutrients , 2013, DOI: 10.3390/nu5093684
Abstract: Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity of the whole fruit. To determine if these results are translatable to humans, we carried out a randomized human study comparing the bioavailability of vitamin C from kiwifruit with that of a vitamin C tablet of equivalent dosage. Thirty-six young non-smoking adult males were randomized to receive either half a gold kiwifruit ( Actinidia Chinensis var. Hort 16A) per day or a comparable vitamin C dose (50 mg) in a chewable tablet for six weeks. Ascorbate was monitored weekly in fasting venous blood and in urine, semen, leukocytes, and skeletal muscle ( vastus lateralis) pre- and post-intervention. Dietary intake of vitamin C was monitored using seven day food and beverage records. Participant ascorbate levels increased in plasma ( P < 0.001), urine ( P < 0.05), mononuclear cells ( P < 0.01), neutrophils ( P < 0.01) and muscle tissue ( P < 0.001) post intervention. There were no significant differences in vitamin C bioavailability between the two intervention groups in any of the fluid, cell or tissue samples tested. Overall, our study showed comparable bioavailability of synthetic and kiwifruit-derived vitamin C.
Lower lid entropion secondary to treatment with alpha-1a receptor antagonist: a case report
Salman Waqar, Peter Simcock
Journal of Medical Case Reports , 2010, DOI: 10.1186/1752-1947-4-77
Abstract: A 74-year-old Caucasian man was started on alpha 1-a receptor antagonist (Tamsulosin) treatment for benign prostatic hypertrophy. Eight days later, he presented to the ophthalmology unit with a right lower lid entropion which was successfully treated surgically with a Weiss procedure.We report a case of lower lid entropion that may be secondary to the recent use of an alpha-1a blocker (tamsulosin). This can be explained by considering the effect of autonomic blockade on alpha-1 receptors in the Muller's muscle on a patient that may already have an anatomical predisposition to entropion formation due to a further reduction in muscle tone.The use of alpha-1a receptor antagonists (tamsulosin) is widely accepted in the treatment of benign prostatic hypertrophy (BPH). It has previously been implicated as a causative agent in the intra-operative floppy iris syndrome due to its effects on smooth muscle. We report a case of lower lid entropion that may be related to a patient commencing treatment with tamsulosin.A 74-year-old Caucasian man presented to the ophthalmology outpatient clinic with a five-day history of a heavy and sore right eye. His past ocular history included cataract surgery and left penetrating keratoplasty for Fuch's endothelial dystrophy. He was maintained on long term flurometholone eye drops once a day in his left eye. He also had been prescribed timolol eye gel (Nyogel) once a day to the left eye for ocular hypertension. His past medical history included paroxysmal atrial fibrillation and hypercholesterolemia. Other regular medications included oxazepam, clopidogrel, lanzoprazole, flecainide acetate and sildenafil. Eight days prior to presentation to the eye clinic, our patient consulted a urologist with complaints of frequency of micturition and had been started on tamsulosin (Flomaxtra XL) 0.4 mg once a day with good response.On examination, he was found to have visual acuities of 6/9 with glasses improving to 6/6 with pinhole in both eyes. A right l
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