EUPATI: Collaboration between patients, academia and industry to champion the informed patient in the research and development of medicines

The value of collaborations and partnerships between different stakeholders to achieve optimum outcomes in the medicines research and development process is being recognised. Historically, there has been a lack of collaboration with patients and many research consortiums consisting mainly of academia and/or industry partners. Although patient experts are able to bring valuable first-hand experience and insights, they might not possess detailed knowledge about medicines research and development to actively participate in the collaboration process. The European Patients’ Academy on Therapeutic Innovation (EUPATI) was established to deliver training to patient experts, and education resourcesto patient advocates and members of the health-interested public across Europe. EUPATI was launched in February 2012 and is a patient-led Innovative Medicines Initiative (IMI) project, with a multi-stakeholder consortium of patient advocates, academia, industry and not-for-profit organisations. Training and educational materials will be used for capacity building among patients, for educating patient advocates and for informing the health-interested public. The successful uptake of EUPATI’s materials will hopefully translate into a new paradigm of increased patient involvement across the entire medicines research and development process, bringing mutual benefits, including better medicines, to all stakeholders

Interactions Between Polycyclic Aromatic Hydrocarbons in the Liver.

Utilising precision-cut rat and human slices, it was demonstrated that individual polycyclic aromatic hydrocarbons (PAHs) are capable of elevating CYP1A1, epoxide hydrolase and glutathione S-transferase mRNA levels and enzyme activity, but to markedly varying extents. It appears that the rat might be a good surrogate animal to human, as far as modulation of CYP1A1 by PAHs is concerned, though some differences were noted in the case of epoxide hydrolase and glutathione S-transferase activity in the two species. There was a positive correlation between binding to the Ah receptor and CYP1A1 modulating potency of PAHs in rat slices, confirming that potent PAHs act as good ligands for this receptor. In interaction studies, exposure of rat slices to binary PAHs mixtures revealed that benzo(a)pyrene-induced CYP1A1 activity was modulated by the presence of other PAHs, both synergistically and antagonistically, and these interactions led to corresponding changes in the metabolism of benzo(a)pyrene to phenols and in the formation of benzo(a)pyrene-DNA adducts. At the mRNA level, in the presence of benzo(a)pyrene, all PAHs caused interactions, either synergistic or antagonistic, in CYP1A1, CYP1B1, epoxide hydrolase and glutathione S-transferase, which were not always paralleled by similar changes in corresponding enzyme activities

Interactions between polycyclic aromatic hydrocarbons in the liver

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Family planning and pregnancy issues for women with systemic inflammatory diseases:patient and physician perspectives

OBJECTIVES: To identify family planning and pregnancy (FPP) issues for female patients of childbearing age living with a chronic inflammatory disease and to assess whether current clinical practice routinely provides adequate support to alleviate these concerns. SETTING: Multinational survey and an analysis of online patient activity. PARTICIPANTS: Premenopausal women (aged 20–45 years; N=969) were surveyed in the USA, the UK, Germany, France, Italy and Spain. Rheumatologists were surveyed in Germany (N=50), France (N=50), Italy (N=50) and the USA (N=100), and gastroenterologists were also surveyed in the USA (N=100). PRIMARY AND SECONDARY OUTCOME MEASURES: Two online surveys were undertaken to identify FPP issues for physicians and patients. The surveys examined the frequency of dialogue on these topics between physicians and patients, alongside assessment of patient satisfaction regarding these conversations. Online analysis identified key themes for patient discussion outside their doctors’ office/clinic/surgery. RESULTS: 32–56% of physicians spontaneously reported having talked about FPP with their female patients of childbearing age. When prompted, the majority of rheumatologists (74–92%) and gastroenterologists (74%) reported having discussed conception/pregnancy with female patients; however, less than half reported consulting their patient's treating general practitioner/gynaecologist about these topics. The majority of patients reported their FPP-related concerns are not adequately addressed/settled during their medical appointments. Furthermore, only 30–40% of patients considered advice/information to be consistent across multiple healthcare professionals. Key online FPP-related patient discussions included disease state, adverse effects, treatment, switch behaviour and wash-out requirements. CONCLUSIONS: Female patients who live with chronic inflammatory disease have important FPP concerns. The majority of patients, however, do not feel that their FPP concerns are adequately addressed in current clinical practice and report that they receive inconsistent advice from the various healthcare professionals who manage different aspects of their care. There is a clear need for provision of up-to-date and consistent information/support to female patients

Modulation of gene expression and DNA-adduct formation in precision-cut liver slices exposed to polycyclic aromatic hydrocarbons of different carcinogenic potency

Polycyclic aromatic hydrocarbons (PAHs) differ markedly in their carcinogenic potencies. Differences in transcriptomic responses upon PAH exposures might improve our current understanding of the differences in carcinogenicity, and therefore gene expression modulation by six PAHs in precision-cut rat liver slices was investigated. Gene expression modulation by benzo[a]pyrene (B[a]P), dibenzo[a,l]pyrene (DB[a,l]P), benzo[b]fluoranthene (B[b]F), fluoranthene (FA), dibenzo[a,h]anthracene (DB[a,h]A) and 1-methylphenanthrene (1-MPA) was assessed after 6- (B[a]P, DB[a,l]P) and 24-h (all compounds) exposure, using oligonucleotide arrays. DNA-adduct formation was determined using (32)P-post-labelling. The effects of PAHs on gene expression and on DNA-adduct formation were much more pronounced after 24-h exposure than after a 6-h exposure. Each compound induced gene expression changes dose-dependently and gene expression profiles were generally compound-specific. B[a]P, B[b]F and DB[a,h]A displayed comparable gene expression profiles, and so did DB[a,l]P, FA and 1-MPA. Only the carcinogenic PAHs (B[a]P, B[b]F, DB[a,l]P and DB[a,h]A) induced the oxidative stress pathway. DNA-adduct levels were: DB[a,l]P >> B[a]P > B[b]F >/= DB[a,h]A > FA >/= 1-MPA. The expression of only a few genes was found to correlate significantly with DNA-adduct formation, carcinogenic potency or Ah-receptor binding capacity (the last two taken from literature). These genes differed between the parameters. Our results indicate that PAHs generally induce a compound-specific response on gene expression and that discrimination of carcinogenic from non-carcinogenic compounds is partly feasible using this approach. Only at a specific pathway level, namely oxidative stress response, PAHs with high and low carcinogenic potency could be discriminated