Browsing by Author "Cellek, Selim"
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Item Open Access Biochemical and biomedical studies on African walnut (Tetracarpidium conophorum -Mull. Arg.) – a postharvest perspective(Cranfield University, 2015-10) Nkwonta, Chikere Godwin; Terry, Leon A.; Cellek, Selim; Alamar, M. CarmenAfrican Walnut (Tetracarpidium conophorum- Mull. Arg) is a perennial climbing shrub which grows mainly in the Western region of Africa. It is found mainly in Nigeria, Gambia, Sierra Leone, Gabon, Equatorial Guinea and Cameroon as well. The nuts are encased in pods which may contain between 2 to 5 nuts. The seed is enclosed in a hard shell-like case. The nuts are commonly processed by boiling or roasting and consumed as a snack or used as soup thickener. In ethnobotanical medicine, the nut extract is extensively used in decoctions for treatment and/or management of common and chronic ailments such as malaria, dysentery, high blood pressure, diabetes and cancer. The nuts are generally exposed to high temperatures (25 – 37 °C) and relative humidity (RH) which increases susceptibility to fungal contamination and nutrient degradation, hence, raising concerns over product quality and safety. Experiment simulating the common retail postharvest storage and processing practices was conducted to: (i) determine the effects on the fatty acid profile; (ii) assess the impact on the fungal population contaminating the nut shells at different maturity stages, and potential mycotoxigenic implications; (iii) evaluate the cytotoxicity of four extract of the nut on lung cancer (A549) cells; and finally (iv) assay the total phenolic content and profile potential individual phenolic components of the nut. Results indicated the presence of essential and non-essential fatty acids namely; palmitate, oleate, stearate, linoleate, arachidate and α-linolineate with α-linolineate being the most abundant (1.1 – 8.2 mg/g freeze-dry weight). Boiling and roasting generally improved the concentration of the fatty acids best when nuts are cold stored at 5 °C for maximum of 10 days. Potential mycotoxigenic species - Aspergillus section Nigri, Aspergillus flavus/Parasiticus, Fusarium spp. and Penicillium spp. - were frequently isolated from cultured shell pieces of stored nuts. When compared with unprocessed nuts, roasting completely prevented fungal contamination in shell pieces from nuts in the non-stored (NSN) group at early maturity stage, while boiling significantly reduced the level of contamination to about 58 % (P < 0.05). Simulating open market conditions caused 100% fungal contamination in all boiled samples and roasted samples at early maturity. Mycotoxin analysis using Yeast Extract agar (YES) and High Performance Liquid Chromatography (HPLC) - Fluorescence detector (FLD) showed that Aflatoxins - G1 (AFG1), B1 (AFB1), G2 (AFG2), and B2 (AFB2) were produced by 20 isolates with both AFG1 and AFB1 being predominant at concentration ranges 4 – 32,200 and 4 – 22,700 ng/g plug weight, respectively. No Ochratoxin A (OTA) was detected. Phenolic component analysis indicated unprocessed (20.79 ± 1.0 mg gallic acid equivalent per gram freeze-dry weight – GAE/g FDW) samples showed the highest value for total phenolics while both boiling (9.90 ± 1.8 mg GAE/g FDW), and roasting (9.32 ± 2.7 mg GAE/g FDW) reduced the amount by more than 50 % when compared with unprocessed. Potential individual phenolic compounds were unambiguously separated using high performance liquid chromatography – diode array detector (HPLC-DAD). There were no differences between chromatograms of defatted and non-defatted unprocessed, roasted and boiled samples. Cytotoxicity evaluation showed no decrease in cell densities in plates treated with extracts from unprocessed nuts at all concentrations. Diethyl ether-ethyl acetate (10 µg/mL) and n-butanol (1000 and 500 µg/mL) extracts of roasted nuts as well as dichloromethane and water (1, 10 µg/mL) of boiled nuts caused a non-significant decrease of < 10 % in cell densities when compared with the phosphate buffered saline-media control. However, all extracts showed no cytotoxic effect on the A549 cells African walnut is basically produced at subsistence level in Nigeria, but considering the presence of desirable fatty acid profile and phenolic compounds, need for increased industrial scale production is herein recommended. Although fungal attack and potential mycotoxin risk on the nut may be high, retail processing by roasting has prospects to greatly accentuate the risk. Cold storage of the nut may help to improve the shelf life although it may not be cost effective for local farmers in Nigeria and Africa, however, it provides opportunity for export business. Although the nut extracts showed no cytotoxic effect on A549 lung cancer cell lines, there is need to investigate further to confirm it non-cytotoxicity activity on other cancer lines and normal cell lines.Item Open Access The design and evaluation of discrete wearable medical devices for vital signs monitoring(Cranfield University, 2015) Pitts, David Geoffrey; Cellek, Selim; Aspinall, Richard; Sinclair, AlanThe observation, recording and appraisal of an individual’s vital signs, namely temperature, heart rate, blood pressure, respiratory rate and blood oxygen saturation (SpO2), are key components in the assessment of their health and wellbeing. Measurements provide valuable diagnostic data, facilitating clinical diagnosis, management and monitoring. Respiratory rate sensing is perhaps the most under-utilised of all the vital signs, being routinely assessed by observation or estimated algorithmically from respiratory-induced beat-to-beat variation in heart rate. Moreover there is an unmet need for wearable devices that can measure all or most of the vital signs. This project therefore aims to a) develop a device that can measure respiratory rate and b) develop a wearable device that can measure all or most of the vital signs. An accelerometer-based clavicular respiratory motion sensor was developed and compared with a similar thoracic motion sensor and reference using exhalatory flow. Pilot study results established that the clavicle sensor accurately tracked the reference in monitoring respiratory rate and outperformed the thoracic device. An Ear-worn Patient Monitoring System (EPMS) was also developed, providing a discrete telemonitoring device capable of rapidly measuring tympanic temperature, heart rate, SpO2 and activity level. The results of a comparative pilot study against reference instruments revealed that heart rate matched the reference for accuracy, while temperature under read (< 1°C) and SpO2 was inconsistent with poor correlation. In conclusion, both of the prototype devices require further development. The respiratory sensor would benefit from product engineering and larger scale testing to fully exploit the technology, but could find use in both hospital and community-based The design and evaluation of discrete wearable medical devices for vital signs monitoring DG Pitts ii Cranfield University monitoring. The EPMS has potential for clinical and community use, having demonstrated its capability of rapidly capturing and wirelessly transmitting vital signs readings. Further development is nevertheless required to improve the thermometer probe and resolve outstanding issues with SpO2 readings.Item Open Access Investigations of the inflammatory pathogenesis of age related macular degeneration and a therapeutic role for Minocycline(Cranfield University, 2015-03) DaCosta, Joanna; Cellek, Selim; Sivaprasad, SobhaAge related macular degeneration (AMD) is the leading cause of blindness in people over the age of 50 in the western world. The wet form of AMD is associated with choroidal neovascularisation. The pathogenesis of choroidal neovascularisation is complex involving neovascular growth, vascular leakage, hypoxia and inflammation. Evidence suggests that immunological events play a key role in the pathogenesis of AMD. In AMD a chronic low grade inflammatory process may instigate the pathophysiological process culminating in eventual visual loss. Minocycline is a tetracycline derivative with anti-inflammatory in addition to antibiotic effects. This study investigated the effects of minocycline on retinal pigment epithelial cells in culture. Cell viability and apoptosis was studied with flow cytometry. Cells were exposed to glycated albumin and hypoxia as these processes occur during ageing. The effects of minocycline on IL-8 and MCP-1 production from ARPE-19 cells in culture were investigated with enzyme linked immunosorbent assay. The results showed a potential narrow therapeutic window for minocycline to act on retinal pigment epithelial cells. Cell viability decreased rapidly at minocycline doses above 5μM. Minocycline suppressed the production of inflammatory cytokines IL-8 and MCP-1 in cell culture. A clinical trial was conducted to investigate whether combination therapy aimed at targeting different pathways in the AMD disease process would be effective. This trial was powered to determine adverse events when a quadruple therapy ii of reduced fluence photodynamic therapy (PDT), intravitreal ranibizumab, dexamethasone and oral minocycline were used as treatments. The clinical trial demonstrated that anti-VEGF treatment administered in combination with other agents was not as effective as monthly anti-VEGF monotherapy at sustaining visual improvement. However, the trial did demonstrate that combination therapy could be delivered safely. The results demonstrate that minocycline has a potential therapeutic role for the inflammatory changes in neovascular age related macular degeneration.Item Open Access Obesity in pregnancy: risk of gestational diabetes(2018) Balani, Jyoti; Cellek, Selim; Mohareb, Fady R.; Hyer, SteveBackground: Maternal obesity is a risk factor for gestational diabetes and other adverse pregnancy outcomes, but the body fat distribution may be a more important risk factor than body mass index. Pregnancy is an insulin resistant state and more so, in obese women. Metformin could be beneficial in obese pregnant women due to its insulin sensitizing action. The aims of this study are to investigate visceral fat mass as a risk factor for gestational diabetes (VFM study), to develop a mathematical model for the prediction of gestational diabetes in obese women (VFM study) and to examine the effect of metformin on pregnancy outcomes in obese non-diabetic women (MOP Trial). Methods and Results: VFM study: The body composition of 302 obese pregnant women was assessed using bioelectrical impedance. A mathematical model to predict gestational diabetes using machine learning was developed using visceral fat mass which is a novel risk factor in addition to conventional risk factors. 72 of the women developed gestational diabetes (GDM). These women had higher visceral fat mass. Women with a baseline visceral fat mass ≥ 75th percentile, had a 3-fold risk of subsequent gestational diabetes. The mathematical model predicted gestational diabetes with an average overall accuracy of 77.5% and predicted birth centile classes with an average accuracy of 68%. According to the decision tree developed, VFM emerged as the most important variable in determining the risk of GDM and a VFM < 210 was used as the first split in the decision tree. MOP Trial: 133 obese pregnant women were randomised to either metformin or placebo. The pregnancy outcomes were compared in both groups. Insulin resistance was measured in all women. 118 women completed the trial. Metformin did not reduce the neonatal birth weight z-score, which was the primary outcome of the trial or the incidence of large for gestational age babies. However, metformin therapy significantly reduced gestational weight gain, reduced the pregnancy rise in visceral fat mass, and attenuated the expected physiological rise in insulin resistance at 28 weeks gestation. However, this did not result in an overall significant reduction in the incidence of gestational diabetes. There was a trend towards a reduced incidence of gestational diabetes in women with high baseline insulin resistance randomised to metformin. Conclusions: Visceral fat mass is a novel risk factor for gestational diabetes. The mathematical model successfully predicted gestational diabetes. Metformin reduced gestational weight gain and insulin resistance but did not lower the median neonatal birth weight or reduce the incidence of GDM.Item Open Access Urogenital function in morbidly obese men following bariatric surgery(Cranfield University, 2016-01) Aleid, Maha Mustafa; White, Nicola; Cellek, Selim; Muneer, Asif; Ralph, David; Hashemi, MajidIntroduction: Obesity has been suggested to be one of the risk factors for erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Bariatric surgery has been used for the treatment of obesity and has been suggested to have a significant impact on obesity-related conditions such as diabetes mellitus, ED and LUTS. Previous studies have investigated the effect of bariatric surgery on erectile and urological function in obese men; however those studies used long-term time points post-operatively (more than 1 month). Since it is now known that bariatric surgery can potentially induce glycaemic improvement within one week independent of weight loss, this study aimed to investigate the short-term effect in order to test the hypothesis as to whether improvement in urogenital function after bariatric surgery is due to weight loss or whether it is due to glycaemic improvement. Aim: To evaluate the baseline characteristics of patients with erectile dysfunction and to determine the early effects of bariatric surgery on erectile and urological function in morbidly obese men ... [cont.].Item Open Access Vasa Nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers(Wiley, 2013-09-12) Beetson, Karl A.; Smith, Stephanie F.; Munner, Asif; Cameron, Norman E.; Cotter, Mary A.; Cellek, SelimINTRODUCTION The vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. AIM To characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation. MAIN OUTCOME MEASURES Characterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels. METHODS MPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope. RESULTS The neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31-positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra-capsular arterioles and venules, but not the capillaries were innervated by nNOS-positive nerve fibers. CONCLUSIONS This study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels. Beetson KA, Smith SF, Muneer A, Cameron NE, Cotter MA, and Cellek S. Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers. J Sex Med **;**:**-**.