Commercial herbs, spices and their essential oils from Libya were examined for their toxicological and antilisterial properties. In order to achieve this, 153 samples of milk and dairy products were examined for the isolation of L. monocytogenes and other Listeria spp. and also for their general microbiological qualities. The latter were found to conform to European and American microbiological specifications. Listeria monocytogenes was not isolated from any of the products, but isolated from swabs of the floor of a Glasgow dairy factory and they were identified as serotypes 1I2b and 4b. However, L. seeligeri and L. grayi were isolated from ice cream samples at (0.7 % of the total products). Studies on the growth and survival conditions (salt concentration, pH, temperature and atmospheres) of the isolates and 5 typed cultures of L. monocytogenes varied. The susceptibilities of L. monocytogenes to gentamicin (30 Jlglml) , kanamycin (25 Jlglrnl) , penicillin G (30 Jlglml) , tetracycline (25 Jlglrnl) , streptomycin (10 units), ampicillin (10 units) and erythromycin «0.005-1.0Jlglml); the susceptibilities were within the range of the breakpoints of Minimum Inhibitory Concentration (MIC). The MIC ranged from <0.005 to 148 Jlglml for all the antibiotics tested. The susceptibilities of L. monocytogenes to probiotic bacteria included B. bifidum 0795, B. breve NCIMB 2258, B. adolescentis NCIMB 2204, Lb. bulgaricus NCFB 1489 and Lb. plantarum DSM 12028 were 100, 57, 34, 34 and 28% respectively. However, the susceptibilities of L. seeligeri and L. grayi to B. adolescentis NCIMB 2204, B. breve NCIMB 2258, B. bifidum 0795, Lb. plantarum DSM 12028, Lb. bulgaricus NCFB 1489 and Lb. acidolescentis NCIMB 2204 were 100,100, 100, 50, 50 and 50 % respectively. The antilisterial activity of the water extracts was lower than the essential oils. The MIC value of clove, mustard green and black seed oils were < 0.01 - 1.1, 0.019 - 0.43 and 0.09 - 0.85 Jlglml respectively and 625.00 Jlglml for cinnamon and thyme oils. In contrast, garlic, coriander, mustard seed, castor and red chili oils had no antilisterial activity against L. monocytogenes, L. seeligeri and L. grayi. However, chili oils in diethyl ether had antilisterial activity against L. monocytogenes, L. seeligeri and L. grayi. The cytotoxic effects of the essential oils showed that the MIC of clove oil was less than the inhibition concentrations of 50% (lCso) listerolycin 0 (LLO) which affected L. monocytogenes isolates, but did not have any effect on the cell lines used (Vero and Hep_2

No description available.

No description available.

Epithelial ovarian cancer (EOC) accounts for over 80% of ovarian carcinomas. More than two-thirds of patients present with metastatic disease resulting in a poor five year survival of 25&37. Surgery is the mainstay of treatment; subsequently the majority of patients receive platinum based chemotherapy regimes. Although chemotherapy may improve progression free survival, it has little impact on overall survival. CA125 has an established role in monitoring response to chemotherapy and providing a lead time to clinical relapse. Its value in prognosis, however, requires clarification. Not all patients express CA125, therefore complementary tumour markers have been intensively sought. The most promising antigenic molecule to date is polymorphic epithelial mucin, against which numerous monoclonal antibodies have been raised. Using several of these antibodies, this thesis investigated the role of the following mucin antigens in EOC; HMFG<SUB>2</SUB>, CA153, CA724, and CA199. In addition, tumour-associated trypsin inhibitor (TATI) and p185, the glycoprotein encoded for by the neu (c erb B2/HER-2) oncogene, were evaluated. Double-determinant immunoassay was the most common method of antigen quantitation. An ELISA was developed for HMFG<SUB>2</SUB> 'in-house', while the remaining markers were measured using commercial assay kits. 1237 blood samples were collected post-operatively from April 1984 to July 1989 from 250 EOC patients. After retrospective clinical documentation, a database consisting of each patient's case history and serial serum marker levels was developed in collaboration with Unilever Research to perform statistical analyses. CA125 was elevated in a greater proportion of patients with all FIGO stages and histological tumour types than all other markers. Whilst serum p185 was elevated in very few patients, there were insufficient data (the major restriction being cost) to assess the clinical correlates of CA153, CA199, CA724 and TATI. HMFG<SUB>2</SUB> showed most promise and was therefore evaluated in more detail.

Ethnobotanical fieldwork was carried out in New Guinea. An antibacterial field assay kit was developed using freeze-dried strains of <i>S. epidermidis </i>and <i>E. coli</i> which allowed plants used in traditional medicines to be screened in situ without having to take them back to a laboratory. This approach identified <i>Lunasia amara </i>(Blanco) as a candidate species; the use of its bark by tribes of the Whitman Range to treat tropical ulcers, supported by clear zones of inhibition with <i>S. aureus.</i> Samples of the bark were collected for analysis and through activity-guided fractionation, the anti- <i>S. aureus </i>activity of the bark extract was pinned down to a single well resolved HPLC peak (MIC <i>S. aureus </i>NCTC 6571 64μg/ml) which subsequent NMR analysis revealed to be the quinoline alkaloid lunacridine; 2’-<i>O</i>-trifluoroacetyl lunacridine was found to be a more stable derivative however. Lunacridine’s planar cationic structure suggested it might act as a DNA intercalator; 220μM giving 50% binding in an ethidium bromide displacement assay. This in turn suggested DNA topoisomerase II as a likely target for the compound which was confirmed with a kDNA decatenation assay revealing complete inhibition of the enzyme at 5μM. Cell viability assays with MRC-5, H226 and HELA cells showed the compound to be cytotoxic in a time dependent manner producing non-linear dose response curves indicative of a topoisomerase poison mode of action. Activation of the apoptosis pathway enzymes caspase 3/7 was also detected, reaching maximal activity between 24 and 48 hours for the H226 cell line. Thus, lunacridine does not represent a selective antibiotic but with the right structural modifications could be developed as an antineoplastic agent.

Melissa and Lavender essentials oils have been shown to have antiagitation and potential pro-cognitive properties. Previous studies have shown these oils to display potential pharmacological effects upon the GABAA receptor, AMPA receptors and voltage-gated sodium channels. In this study, the major neuroactive constituents which belong to both essential oils and the mechanisms which underpin the behavioural effects of these oils have been identified. One of the major component(s) of Melissa oil, trans-ocimene, profoundly inhibited [3sS]-t-butylbicyciophosphorothionate ([3SS] TBPS) binding to native gamma-aminobutyric acid (GABAA) receptors in a concentration dependent manner with an ICsoof 40 !-1M.No clear evidence was found for any of the major components of the oils being candidate sodium channel blockers. In this study, the putative AMPAkine effect of Melissa (Mo) essential oil (Eo) was also investigated on neuronal cultures and following in vivo exposure (acute- and chronic- treatments) using an Alzheimer's diseasemouse model (TASTPM). Neither protocol demonstrated clear effects of Mo on transmembrane-regulated protein gamma 8 (TARPy8)-, glutamate receptor subunit 2 (GluA2) or brain-derived neurotrophic factor (BDNF) expression. Overall, this study suggested the dominating mechanism of Mo is neuronal depression, via blockade of voltage-gated sodium channels confirmed in parallel electrophysiology studies. TASTPM mice displayed a high level of anxiety which was not overcome by either acute or chronic treatments with Mo, resulting in little beneficial effects upon learning and memory performance in both novel object recognition (NOR) and 3D maze tests. However, the NOR experiment indicated beneficial cognitive effects of Sunflower oil which are worthy of further study. In conclusion, this thesis provides new evidence for the rationale use of Melissa oil and its constituent(s) as anti-agitation agents and suggests their potential for treatment of other neurological disorders, such as epilepsy and chronic neuropathic pain disorders

No description available.

In this study we used standard cell culture techniques using three prostate cancer cell lines DU145, LNCaP and PC3. Green tea extract (EGCG) alone induced apoptosis in the three cell lines in a dose-dependent manner. DHT stimulated growth in LNCaP cells, but the presence of DHT, sensitised these cells to apoptosis induced by EGCG or an IGF-I receptor inhibitor (AG1024). We also found that EGCG via its antioxidant action negated the efficacy of radiotherapy through the induction of superoxide dismutase enzymes. Among the three ECM used, fibronectin but not laminin or vitronectin activated a survival pathway that protected DU145 but not LNCaP prostate cancer cells against ceramide and Docetaxel-induced apoptosis but not that induced by radiotherapy. This survival effect involved the insulin-like growth factor (IGF-I) and β1 integrin receptors and was associated with an increase in the recruitment of the β1 integrin receptor to a complex containing the IGF-IR and protein receptor for activated C kinase (RACK-1) and an increase in the abundance of a MAPK-phosphatase, MKP-1. Our study has shown that EGCG can act as a chemopreventive agent in presence of androgen but it may not provide any additive effect in prostate cancer treated with antiandrogens. In addition we concluded that drinking green tea prior to radiotherapy treatment could reduce its efficacy. We have also shown that the susceptibility to chemotherapy might be improved by targeting either the IGF-I or β1 integrin receptors.

The health benefits of green tea catechins (GTC) are becoming increasingly recognised. Amongst the proposed benefits are a reduction in atherosclerosis and cardiovascular disease risk, which is thought to be in part attributable to the maintenance of endothelial function and vascular homeostasis. Catechol-O- methyltransferase (COMT) is centrally involved in GTC metabolism, with a valine to methionine amino acid substitution at position 108/158 (soluble/membrane-bound form) of the protein reported to result in a reduction in enzyme activity. The current research investigated the impact of the COMT genotype on, GTC metabolism, and the acute impact of GTC on endothelial function and its associated phenotype. Firstly, a pilot human study was performed primarily investigating the acute effects of COMT genotype on GTC metabolism. Twenty participants, prospectively recruited according to COMT genotype, were given an acute dose of GTC extract followed by the collection of frequent blood samples to assess plasma GTC and associated metabolites. Although no significant differences between genotype groups were found, a tendancy towards a difference in EGCG methylation was observed. The study design also included a high carbohydrate breakfast meal, consumed 60 min after the green tea catechin extract. Subsequent assessment of plasma glucose and insulin identified an unexpected difference in insulin response between genotype groups. Thus, an insulin sensitivity assessment was incorporated into the main human study design to investigate this further. The main human study, a randomized, placebo- controlled, double-blind acute intervention study involved fifty volunteers, twenty five of each homozygous genotype. Vascular function, assessed by digital volume pulse (DVP) and Endo-PAT, and insulin sensitivity, assessed by an oral glucose tolerance test, was measured before and 90-105 min after 836 mg green tea extract or placebo. Blood samples were collected at regular intervals throughout the study day together with a 24 h urine collection. Firstly, we reported no significant treatment differences for vascular function for the entire study population group. However, genotypic differences were evident, with the proposed low activity COMT genotype group demonstrating an attenuation of the DVP reflection index (measure of small arterial tone) after the green tea extract compared to placebo (p = 0.014). Secondly, we found no significant treatment differences in insulin sensitivity and resistance for the entire study population group. Although, evidence was found for an improvement in the fasting insulin sensitivity index HOMA, in the proposed low activity COMT genotype group after the green tea extract compared to placebo (p = 0.043). Finally, concentrations of methylated EGC in the urine was significantly different between genotype groups with the proposed low activity COMT genotype group demonstrating a lower concentration (p = 0.049). No significant differences in the appearance of GTC and EGCG metabolites in the plasma between COMT genotype groups were evident. Together, our data suggests some improvements in vascular function and markers of insulin sensitivity with GTC supplementation, an effect which appears to be influenced by the COMT genotype. However, the effect size was modest and of questionable clinical relevance.

Despite evidence from the animal literature on the benefits of flavonoids on cognition, research with human subjects is limited, particularly with regard to flavonoid-rich blueberries. This research investigated the acute effects of a blueberry beverage (containing - 579mg of flavonoids) on cognition, by conducting randomised controlled cross-over intervention studies with healthy younger (N=19) and older (N=IS) adults. Cognition was measured at baseline, two and five hours post drink. Vascular reactivity and brain-derived neurotrophic factor (BDNF) were also measured, one hour post drink. A magnetic resonance imaging (MRI) study was conducted to determine whether the blueberry drink would lead to increased cerebral blood flow (CBF). Univariate statistical analysis revealed improvement in updating ability in the younger adults and immediate word recognition in the older group, following the blueberry compared to control drink, whereas susceptibility to priming in the older adults was reduced. However, for the majority of the univariate analyses, there was no significant effect of the intervention, which was also true following multivariate analysis of the cognitive measures. In both groups, whilst there was no effect of the intervention on vascular reactivity, BDNF levels were higher following the blueberry compared to control drink. Whilst results of the MRI study revealed no effect of the intervention on whole brain or gray matter CBF, there was increased CBF in different regions of the occipital cortex post consumption of the drinks, however more interestingly, there was a greater increase in CBF in areas of the precentral and middle frontal gyrus (frontal lobe) as well as the angular gyrus (parietal lobe) following the blueberry compared to control drink. In conclusion, acute blueberry supplementation led to improvement in some cognitive abilities, possibly due to the impact of flavonoids on cell signalling pathways (e.g. those involving BDNF), in addition to vasodilatory properties and subsequent CBF increases.