Luciferase inhibition by a novel naphthoquinone.

The novel naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (hereafter called TU100) was created as a potential chemotherapeutic agent. Previous work showed it is an irreversible inhibitor of type I and II topoisomerases that alkylates specific enzyme thiols. While analyzing the effect of TU100 on cancer cells, we discovered it is a potent inhibitor of luciferase derived from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Pre-incubation experiments showed that TU100 does not irreversibly inactivate luciferase, indicating its mechanism is different from that observed with topoisomerases. Firefly luciferase generates light using ATP and luciferin as substrates (bioluminescence). An examination of TU100 inhibition at varying substrate concentrations revealed the drug is uncompetitive with respect to ATP and competitive with respect to luciferin. The TU100 binding constant (K(I)) is 2.5±0.7 µM as determined by Dixon plot analysis. These data suggest TU100 specifically binds the luciferase-ATP complex and prevents its interaction with luciferin. Given the novel structure of TU100, unique mechanism of action, and ability to target luciferase from different species, these results identify TU100 as an important new reagent for investigating and regulating bioluminescent enzymes.

Task-specific practice of dressing tasks in a hospital setting improved dressing performance post-stroke: a feasibility study.

BACKGROUND: Practise of personal activities of daily living, including dressing improves outcomes for people living at home after a stroke. Less is known about dressing outcomes for hospital inpatients. AIM: This study aimed to investigate the feasibility and outcomes of a group-based, task-specific dressing retraining programme for inpatients post-stroke. METHODS: A pre-post single group study design was used. Retrospective data were collected for stroke inpatients admitted to one hospital between 2007 and 2009. Participants attended a one-hour dressing group twice weekly during admission, supervised by occupational therapists. Each participant had one or more dressing goals. Scores on the Functional Independence Measure (FIM) upper and lower body dressing items were compared at baseline and at discharge. RESULTS: Of 119 participants who received group-based training, a mean improvement was found of 2.2 FIM points (95% CI 1.9-2.5, P = 0.0001) for upper body dressing (range 0-7), 2.7 FIM points (95% CI 2.3-3.1, P = 0.0001) for lower body dressing (range 0-7) and 5.2 FIM points (95% CI 4.5-6.0, P = 0.0001) for total dressing scores (range 0-14). Of 242 goals recorded, 48% focussed on shirt/upper body dressing, 35% on pants/shorts, 11% on socks and shoes and 13% involved buttons/fastenings. CONCLUSIONS: Task-specific practice of dressing tasks in a group setting was feasible and made clinically significant differences to dressing performance during inpatient rehabilitation. More rigorous methods of investigation are required in future to minimise selection, measurement and intervention biases.