Oral health in residential aged care : perceptions of nurses and management staff

Aim: This study aimed to explore the perceptions of residential aged care nursing and management staff regarding oral care, to develop strategies to improve the oral health of aged care residents. Design: A qualitative approach was used. Methods: Two focus groups were conducted with nursing and management staff at two residential aged care facilities and transcripts were thematically analysed. Results: All staff had an awareness of the importance of oral health; however, they highlighted the significant challenges in the current system that affect implementation of oral health training and practice guidelines in the residential aged care facility. High staff turnover, time constraints, difficulties in accessing dental services and working together with residents, their families and external staff were barriers to providing oral health care. Staff highlighted the need for formalized clinical guidelines and processes and efficient dental referral pathways to create a more cohesive system of care

E. coli NfsA: an alternative nitroreductase for prodrug activation gene therapy in combination with CB1954

Prodrug activation gene therapy is a developing approach to cancer treatment, whereby prodrug-activating enzymes are expressed in tumour cells. After administration of a non-toxic prodrug, its conversion to cytotoxic metabolites directly kills tumour cells expressing the activating enzyme, whereas the local spread of activated metabolites can kill nearby cells lacking the enzyme (bystander cell killing). One promising combination that has entered clinical trials uses the nitroreductase NfsB from Escherichia coli to activate the prodrug, CB1954, to a potent bifunctional alkylating agent. NfsA, the major E. coli nitroreductase, has greater activity with nitrofuran antibiotics, but it has not been compared in the past with NfsB for the activation of CB1954. We show superior in vitro kinetics of CB1954 activation by NfsA using the NADPH cofactor, and show that the expression of NfsA in bacterial or human cells results in a 3.5- to 8-fold greater sensitivity to CB1954, relative to NfsB. Although NfsB reduces either the 2-NO2 or 4-NO2 positions of CB1954 in an equimolar ratio, we show that NfsA preferentially reduces the 2-NO2 group, which leads to a greater bystander effect with cells expressing NfsA than with NfsB. NfsA is also more effective than NfsB for cell sensitisation to nitrofurans and to a selection of alternative, dinitrobenzamide mustard (DNBM) prodrugs

Repeated cycles of Clostridium-directed enzyme prodrug therapy result in sustained antitumour effects in vivo

The unique properties of the tumour microenvironment can be exploited by using recombinant anaerobic clostridial spores as highly selective gene delivery vectors. Although several recombinant Clostridium species have been generated during the past decade, their efficacy has been limited. Our goal was to substantially improve the prospects of clostridia as a gene delivery vector. Therefore, we have assessed a series of nitroreductase (NTR) enzymes for their capacity to convert the innocuous CB1954 prodrug to its toxic derivative. Among the enzymes tested, one showed superior prodrug turnover characteristics. In addition, we established an efficient gene transfer procedure, based on conjugation, which allows for the first time genetic engineering of Clostridium strains with superior tumour colonisation properties with high success rates. This conjugation procedure was subsequently used to create a recombinant C. sporogenes overexpressing the isolated NTR enzyme. Finally, analogous to a clinical setting situation, we have tested the effect of multiple consecutive treatment cycles, with antibiotic bacterial clearance between cycles. Importantly, this regimen demonstrated that intravenously administered spores of NTR-recombinant C. sporogenes produced significant antitumour efficacy when combined with prodrug administration

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Lack of effect of aspartame or of -phenylalanine on photically induced myoclonus in the baboon, Papio papio

The effects of large doses of -phenylalanine and of aspartame on seizure susceptibility and severity have been assessed in baboons Papio papio from Senegal which show photosensitive epileptic responses similar to primary generalised epilepsy in man. -Phenylalanine, 50, 150 or 450 mg/kg, or aspartame, 300 or 1000 mg/kg, were administered orally. Peak plasma -phenylalanine concentrations of approximately 2000 [mu]moles/1 occurred 1-4 h after the highest dose of -phenylalanine or aspartame. The plasma -phenylalanine to large neutral amino acid ratio increased approximately 30-fold at this time. Compared with water administration there were no changes in epileptic responses 1-5 h after either treatment. In this primate model of epilepsy acute increases in plasma phenylalanine concentration are neither pro- nor anticonvulsant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27853/1/0000264.pd

Live imaging of leukocyte recruitment in a zebrafish model of chemical liver injury

Studying early immune responses to organ damage in situ requires animal models amenable to intravital imaging. Here, we used transparent zebrafish larvae, a powerful animal model for innate immunity, to measure leukocyte recruitment to damaged livers. Bath application of metronidazole (Mtz) to fish expressing nitroreductase (NTR) under a liver-specific promoter damaged the organ within 24 hours causing oxidative stress, distorted liver morphology, accumulation of TUNEL-positive cells, and transcriptional upregulation of apoptotic and antioxidant genes. Inflammatory gene transcription in damaged hepatocytes was attenuated. In line with predominant apoptosis, macrophages were massively recruited into Mtz/NTR-damaged livers. By contrast, neutrophil infiltration was more variable and delayed, consistent with less abundant necrosis and an attenuated inflammatory capacity of damaged hepatocytes