The development of 19F NMR as a tool for analysing steroid degradation in active urine samples

Abstract The detection of prohibited performance-enhancing drugs in sports is often carried out using urine samples. The reason for this is that urine samples can be collected under non-sterile conditions and do not require the presence of a sanctioned medical officer. Improper storage of the urine samples from athletes can lead to microbial contamination, which can cause changes in the steroids profile, leading to false positive or false negative results for a particular athlete. To address this problem, a new analytical method was proposed that employs a fluorinated steroid as an internal standard and fluorine-19 nuclear magnetic resonance spectroscopy (19F-NMR) spectroscopy to identify both microbial and thermally-induced changes in the urine samples. In Chapter 2, synthesis of fluorinated steroids was carried out using method that involve the reaction of Selectfluor® with enolates/enols of steroids. A range of fluorinated steroids was prepared (2 novel F-steroids) in moderate yields and varying diastereoselectivities. Several synthesised steroids were recrystallized and crystals suitable for X-ray were obtained. In Chapter 3, selected fluorinated steroids were incubated with microorganisms such as Escherichia coli, Bacillus subtilis, Bacillus megaterium and Streptomyces griseus. Fluorinated steroids were transformed to various oxidised metabolites upon incubation with Streptomyces griseus. Escherichia coli did not produce any metabolites due to lack of cytochrome P450 enzymes. Incubation of Bacillus subtilis and Bacillus megaterium was not successful and therefore metabolites were not detected. In Chapter 4, hydroxy steroids were reacted with pentafluoropyridine (PFP) to form perfluoropyridine ethers in good yield. Several novel steroids were synthesised and the structures of 4 perfluoropyridine ethers were confirmed for the first time by X-ray structure. It was found that the hydroxy steroid PFP adducts have very similar 19F NMR spectra however they can be distinguished using this technique. This novel derivatisation technique could be potentially used for identification of hydroxy steroids in biological material by 19F NMR

A foreign hotel in London: the history of Hilton's negotiation of legitimacy in the 'swinging sixties'

Whilst theories of business internationalisation assert that foreignness poses challenges to multinational companies’ subsidiaries operating abroad, historical study of Hilton International’s expansion in the 1960s suggests otherwise. In its early internationalisation Hilton International transferred abroad its institutional ownership advantages including corporate philosophy and culture; its practices, policies, processes and work systems and product design. Despite claims of social embeddedness, the London Hilton was perceived to be a typically American hotel. Analysis of Hilton’s expansion strategy suggests that the company used its foreignness as a differentiating factor. This paper contributes to the limited business history research in the area of internationalisation and knowledge transference. Historical analysis of Hilton’s internationalisation contradicts the institutionalism’s assumption that multinationals must adapt to local institutional settings. This paper enhances the notion that playing the ‘foreignness’ game can lead to comparative global advantage

Expression of epidermal growth factors and apoptosis markers in pancreatic ductal adenocarcinoma.

BACKGROUNDEpidermal growth factor family members: EGF, EGFR and the c-erbB-2(HER-2/neu) are involved in the growth of pancreatic ductal carcinoma, its invasiveness and metastases. Similarly, proteins regulating apoptosis can influence the development of pancreatic cancer. The aim of our study was to assess the expressions of EGF, EGFR, c-erbB-2, Bax and Bcl-xL in comparison with anatomo-clinical parameters. We also analyzed the relationship between the epidermal growth factors and apoptosis-regulating proteins.MATERIALS AND METHODSThe levels of these proteins were determined immunohistochemically in 29 pancreatic ductal carcinoma cases.RESULTSWe found no correlation of EGF, EGFR, c-erbB-2, Bax and Bcl-xL with age and gender of patients, or histological type and grade of malignancy (G). However, we observed a very strong correlation between EGF, EGFR, Bax, Bcl-xL and lymph node metastases (p=0.000, p=0.001, p=0.008, p=0.012, respectively) and between EGF, EGFR and distant metastases (p=0.002, p=0.008, respectively). Moreover, we found a correlation between Bcl-xL and c-erbB-2 (p=0.030) and between EGF and Bax (p=0.041).CONCLUSIONSThese investigations seem to suggest that both epidermal growth factors (EGF, EGFR) and apoptosis-regulating proteins (Bax and Bcl-xL) play an essential role in lymph node involvement. Moreover EGF and EGFR are involved in distant metastases. The apoptosis markers appear to cooperate with epidermal growth factor proteins in the process of tumor spread

Emergency care of the dialysis patients

End stage renal disease (ESRD) is one of the major health care burdens worldwide. Emergency staff are well aware of the frequent use of their services by dialysis patients. In this article we discuss the urgent and serious medical problems that bring the dialysis patient to the emergency department (ED), and the special considerations in the management of such patients in the acute care setting. The main medical problems in dialysis patients presenting to the emergency department are as follows: emergent acid-base and electrolyte disorders; fever; cardiovascular emergencies; dyspnea; angina/chest pain; anemia and emergencies related to access. In conclusion, hemodialysis (HD) and peritoneal dialysis (PD) patients frequently utilize ED services because of their proneness to a variety of emergency medical problems

Correlation of c-erbB-2, EGF and EGFR expression with postoperative survival of patients with advanced carcinoma of the stomach.

The c-erbB-2 (HER-2/neu), EGF and EGFR (erbB-1) proteins, members of the epidermal growth factor receptor family, play a role in cell growth by binding to cell membrane receptors. The aim of the current study was to evaluate the expression of c-erbB-2, EGF and EGFR in advanced gastric carcinoma and to analyze its relationship with chosen anatomo-clinical parameters and prognosis. Standard avidin-biotin-peroxidase was used for c-erbB-2, EGF and EGFR immuno-histochemical staining (Novostain Super ABC Kit Universal); anti-human c-erbB-2 protein monoclonal antibody NCL-cerbB-2-316, anti-Epidermal Growth Factor monoclonal antibody (clone EGF-10) and EGFR goat polyclonal IgG (p-EGFR). A statistically significant correlation was found between c-erbB-2, EGF, EGRF expressions in the main mass of tumor and lymph node metastasis (p=0.000; p=0.000; p=0.00001, respectively). Also an association was observed between c-erbB-2 expression and Bormann's and Lauren's classifications (p=0.05; p=0.006, respectively). Similarly, the expression of EGFR in main mass of tumor was correlated with the depth of invasion (p=0.007) and histological differentiation (p=0.04). Moreover, the expression of c-erbB-2 in the main mass of tumor and lymph node metastasis was associated with the age of the patients (p=0.03; p=0.0002 respectively). Strong association was found between the expression of EGRF in lymph node metastasis and histological differentiation (p=0.04). Positive expression of c-erbB-2 in lymph node metastasis was correlated with lymph node involvement (p=0.04). Positive expression of c-erbB-2 in the main mass of tumor and in lymph node metastasis was strongly correlated with postoperative survival (p=0.00001; p=0.003 respectively). We also found a relationship between EGF expression in gastric tumor and survival time (p=0.003). No association was noted between the expression of EGFR in the main mass of tumor and in lymph node metastasis and between the expression of EGF in lymph node metastasis and survival time. Our results suggest that the expression of c-erbB-2 and EGF protein can help predict the postoperative survival time

Helicobacter pylori infection and expressions of EGF, EGFR and c-erbB-2 proteins in gastric carcinoma.

The family of epidermal growth factor (EGF, EGFR, c-erbB-2) plays a pivotal role in gastric cancer progression, invasion and metastasizing. Helicobacter pylori infection is known to contribute significantly to the formation and progression of gastric cancer. However, the mechanisms responsible for this process have not been yet elucidated. We analysed the relationship between H. pylori infection and expression of proteins belonging to the family of epidermal growth factor (EGF, EGFR, c-erbB-2). Fifty-five patients with gastric cancer were analysed for Helicobacter pylori infection. The expressions of EGF, EGFR, c-erbB-2 proteins were determined using an immunohistochemical method. No statistically significant correlation was found between the degree of H. pylori infection and the expressions of EGF, EGFR and c-erbB-2 in gastric cancer. However, c-erbB-2 expression in the main mass of tumour correlated with tumour expression of EGF and EGFR and with c-erbB-2 expression in local lymph nodes. The expression of c-erbB-2 in lymph nodes was statistically significantly related to the expressions of EGF and EGFR both in the main mass of tumour and in lymph nodes. The expression of EGF was found to correlate with EGFR in the main mass of tumour and the expression of EGF in lymph nodes was related to lymph node EGFR level. Our study did not confirm the relationship between H. pylori infection and the expression of epidermal growth factor in gastric cancer