Detection of biogenic amines in pet food ingredients by RP-HPLC with automated dansyl chloride derivatization.

The detection of biogenic amines is of significant interest to the food industry, as they can be used as indicators of food spoilage and they are potentially toxic. Because of their importance, there is a need for automated methods suitable for industry use that can detect a wide range of biogenic amines at sufficient levels for food analysis. In this work, optimized conditions for the automated determination of biogenic amines (histamine, putrescine, cadaverine, spermine, spermidine, tyramine, and tryptamine) derivatized with dansyl chloride are presented. Limits of detection below 0.2 ppm were achieved for seven biogenic amines and percentage recoveries were between 80 and 109% for the seven analytes spiked into meat meal samples. The method is simple and compared well to an existing method for the detection of biogenic amines in pet food ingredients.

The determination and characterisation of 2-naphthyloxycarbonyl chloride derivatised biogenic amines in pet foods.

The need to monitor biogenic amines levels is essential for many areas of the food industry for two main reasons: the caustic nature and potential toxicity of these amines, and the potential to use amine levels as markers for freshness and quality in foodstuffs. Optimised analysis conditions used for the determination of biogenic amines derivatised with 2-napthyloxycarbonyl chloride has been applied to different pet food samples to assess the effectiveness of this method for complex sample matrices. Further to this, the use of high-resolution mass spectrometry has enabled the previously unconfirmed derivatised form of seven biogenic amines to be established. The derivatised forms identified include as mono substituted (tryptamine and histamine), bisubstituted (putrescine, cadaverine and tyramine), trisubstituted (spermidine) and tetrasubstituted (spermine). The methodology of biogenic amine determination was performed successfully to a range of pet food products highlighting the applicability to a variety of complex sample matrices.

Mitoxantrone in combination with an inhibitor of DNA-dependent protein kinase: a potential therapy for high risk B-cell chronic lymphocytic leukaemia.

Defects in the DNA damage response pathway [e.g. del(17p)] are associated with drug-resistant B-cell chronic lymphocytic leukaemia (CLL). We previously demonstrated that over-expression of DNA-dependent protein kinase (DNA-PK) correlates with chemo-resistance and that inhibition of DNA-PK sensitizes CLL cells to chemotherapeutics. Here, we investigated expression of DNA-PK and other proteins that impact on drug resistance, and evaluated the effects of a DNA-PK inhibitor (NU7441) on mitoxantrone-induced cytotoxicity in CLL cells. NU7441 sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization ranging from 2- to 200-fold Co-culture of CLL cells in conditioned stromal medium increased chemoresistance but did not reduce sensitization by NU7441. Mitoxantrone treatment induced γH2AX foci and NU7441 increased their longevity (24 h). NU7441 prevented mitoxantrone-induced autophosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) at Ser 2056, confirming that DNA-PK participates in repair of mitoxantrone-induced DNA damage. del(17p) cases were more resistant to mitoxantrone than del(13q) cases, but were resensitized (7-16 fold) by co-incubation with NU7441. Expression of DNA-PKcs, Ku80, P-glycoprotein and topoisomerase IIß were significantly higher in del(17p) cases. PRKDC mRNA levels correlated with DNA-PKcs protein expression, which predicted shorter survival. These data confirm the potential of DNA-PK as a therapeutic target in poor prognosis CLL.

Infrastructure and operating processes of PIONEER, the HDR-UK Data Hub in Acute Care and the workings of the Data Trust Committee: a protocol paper.

INTRODUCTION: Health Data Research UK designated seven UK-based Hubs to facilitate health data use for research. PIONEER is the Hub in Acute Care. PIONEER delivered workshops where patients/public citizens agreed key principles to guide access to unconsented, anonymised, routinely collected health data. These were used to inform the protocol. METHODS: This paper describes the PIONEER infrastructure and data access processes. PIONEER is a research database and analytical environment that links routinely collected health data across community, ambulance and hospital healthcare providers. PIONEER aims ultimately to improve patient health and care, by making health data discoverable and accessible for research by National Health Service, academic and commercial organisations. The PIONEER protocol incorporates principles identified in the public/patient workshops. This includes all data access requests being reviewed by the Data Trust Committee, a group of public citizens who advise on whether requests should be supported prior to licensed access. ETHICS AND DISSEMINATION: East Midlands-Derby REC (20/EM/0158): Confidentiality Advisory Group (20/CAG/0084). www.PIONEERdatahub.co.uk.

What do ratings on unidimensional pain and emotion scales really mean? A Multidimensional Affect and Pain Survey (MAPS) analysis of cancer patient responses.

The purpose of the study was to determine what dimensions of pain predicted scores on numerical rating scales (NRSs) of Pain, Anxiety, Depression, and Health Expectation in cancer patients. Seventy-one patients with intra-abdominal cancer responded to the Multidimensional Affect and Pain Survey (MAPS) and rated their pain and emotion on the NRSs. Scores on the Pain NRS were predicted by 41% of clusters in the MAPS Somatosensory Pain Supercluster, but by 100% of clusters in the Emotional Pain Supercluster, and negatively by 51% of clusters in the Well-Being Supercluster. The Anxiety and Depression NRSs were each predicted by only the Intense Pain cluster in the Somatosensory Pain Supercluster, but by all of clusters in the Emotional Pain Supercluster. The findings indicate that cancer patients' emotional state is a strong co-determinant of their sensory pain ratings. Negative emotional aspects of pain contribute also to scores on the Anxiety, Depression and Health Expectation NRSs.