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Browsing by Author "Masania, J."

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    Detection and Determination of Methanol and Further Potential Toxins in Human Saliva Collected from Cigarette Smokers: A 1H NMR Investigation
    (2018-01-02) Percival, B.; Wann, A.; Masania, J.; Sinclair, J.; Sullo, N.; Grootveld, Martin
    Introduction/Objectives: The deleterious health effects of tobacco smoking are now widely recognized and documented. High-resolution 1 H NMR analysis of human saliva provides a high level of valuable molecular information regarding the nature and levels of a wide range of both endogenous and exogenous agents therein. This investigation focused on the detection of molecular modifications to the salivary 1H NMR profiles of cigarette smokers following smoking of a single cigarette product. Methods: Cigarette-smoking human participants (6 female, 7 male) provided saliva samples both prior and subsequent to smoking a single cigarette (the former following a 12 hr. overnight fasting/smoking-abstention period). A group of n = 7 non-smoking controls also provided saliva samples before and after a 4.0 min. ‘smoking mimic’ time period.1 H NMR analysis of supernatants derived therefrom was conducted at an operating frequency of 400 MHz. Results: 1H NMR analysis revealed that single cigarette smoking episodes gave rise to substantial increases in the salivary concentrations of methanol (p<10-6) and propane-1,2-diol (p = 2.0 x 10-4), i.e. ca. 40- and 3.2-fold escalations in their mean levels respectively; the identity of methanol was confirmed by GC-MS analysis. As expected, there were no modifications to these tobacco smoking marker levels in control group participants following a corresponding 4.0 min. non-smoking period. Conclusions: 1H NMR analysis of human saliva provided much valuable information on the infiltration of toxins and further agents from cigarette smoke into this biofluid. The marked elevations in salivary methanol levels observed are of much concern in view of its documented toxicological properties and adverse health effects.
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    Dicarbonyl stress in clinical obesity
    (Springer, 2016-06-24) Masania, J.; Malczewska Malec, M.; Razny, U.; Goralska, J.; Zdzienicka, A.; Kiec-Wilk, B.; Gruca, A.; Stancel-Mozwillo, J.; Dembinska-Kiec, A.; Rabbani, N.; Thornalley, P. J.
    The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure
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    Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models
    (MDPI, 2018-12-27) Percival, B.C.; Grootveld, Martin; Gibson, M.; Osman, Y.; Molinari, M.; Jafari, F.; Sahota, T. S.; Martin, M.; Casanova, F.; Mather, M.L.; Edgar, M.; Masania, J.; Wilson, Philippe B.
    Novel sensing technologies for liquid biopsies offer promising prospects for the early detection of metabolic conditions through omics techniques. Indeed, high-field nuclear magnetic resonance (NMR) facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognise unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimised experiments, including α-glucose (≤2.8 mmol/L) and acetone (25 µmol/L), and additionally in readily accessible biofluids, particularly human urine. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics applications, and offer a perspective on the future of this technique appealing to ‘point-of-care’ applications.
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    Teaching Analytical Chemistry to Pharmacy Students: A Combined, Iterative Approach
    (ACS, 2017-11-14) Masania, J.; Grootveld, Martin; Wilson, Philippe B.
    Analytical chemistry has often been a difficult subject to teach in a classroom or lecture-based context. Numerous strategies for overcoming the inherently practical-based difficulties have been suggested, each with differing pedagogical theories. Here, we present a combined approach to tackling the problem of teaching analytical chemistry, with particular emphasis on inherently practice-based cohorts such as pharmacists. A composite visual, interactive, didactic, and practical approach is presented, in which students are able to fully engage with the teaching/training materials within numerous contexts. From unit evaluations, student–staff liaison committee feedback, and an analysis of marks issued from virtual learning environment quizzes, the enthusiasm of the students for such an approach is found to correlate with their understanding of the topic. The broad outline of the course is included as an example.
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