BACKGROUND Individuals with low activity of a key metabolic enzyme, thiopurine methyl transferase (TPMT), are more susceptible to azathioprine-induced myelosuppression. AIM To determine the pattern of use of TPMT activity estimation, with respect to azathioprine use, by medical practitioners in the UK. DESIGN Retrospective analysis of assay use. METHODS We analysed all test results (n=329...

The thiopurine antimetabolites 6-thioguanine and 6-mercaptopurine are important chemotherapeutic drugs in the treatment of childhood acute lymphoblastic leukaemia. Measurement of metabolites of these thiopurines is important because correlations exist between levels of these metabolites and the prognosis in childhood acute lymphoblastic leukaemia. The reversed-phase method for the determination...

OBJECTIVES To determine the activity of glutathione transferase and to measure the S-methylcysteine adducts in blood proteins, after acute inhalation exposure to methyl bromide. To examine the influence of the polymorphism of glutathione-S-transferase theta (GSTT1) on the neurotoxicity of methyl bromide. METHODS Two workers acutely exposed to methyl bromide with inadequate respiratory protect...

BACKGROUND AND AIMS Thiopurines are effective to induce and maintain remission in inflammatory bowel disease (IBD). The methyl thioinosine monophosphate (meTIMP)/6-thioguanine nucleotide (6-TGN) concentration ratio has been associated with drug efficacy. Here we explored the molecular basis of differences in metabolite profiles and in relation to disease activity. METHODS Transcriptional prof...

The thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well-established agents for the treatment of leukaemia but their main modes of action are controversial. Thiopurine methyltransferase (TPMT) metabolises thiopurine drugs and influences their cytotoxic activity. TPMT, like DNA methyltransferases (DNMTs), transfers methyl groups from S-adenosylmethionine (SAM) and generates...

BACKGROUND AND AIMS A drug interaction between infliximab and azathioprine has previously been reported in Crohn's disease patients: the concentration of the main active thiopurine metabolites, the 6-thioguanine nucleotides (6-TGN), increased 1-3 weeks after the first infliximab infusion by 50% compared to baseline. The aim of this prospective study was to determine the effect of adalimumab on ...

Background The efficiency and safety of the thiopurine therapy rely on the concentration of patient's cytotoxic thioguanine nucleotides (TGN), which in turn depend on the deactivation of thiopurine drugs by thiopurine S-methyltransferase (TPMT). The activity of TPMT largely depends on the presence of genetic polymorphisms. Determination of mutations in the TPMT gene before starting 6-mercaptopu...

1 Abbreviations used: [methyl-C]AdoMet, S-adenosyl-L-[methyl-C]methionine; [methyl-H]AdoMet, S-adenosyl-L-[methyl-H]methionine; aDMA, asymmetric x-N,N-dimethylarginine; AdoMet, S-adenosyl-L-methionine; AdoHcy, S-adenosylL-homocysteine; CID, collision-induced dissociation; DMA, dimethylarginine; DTT, dithiothreitol; ESI, electrospray ionization; ETD, electron-transfer dissociation; FPLC, fast pe...

We present the first presteady state kinetic analysis of an S-adenosylmethionine-dependent enzyme. The target enzyme is the bacterial EcoRI DNA methyl-transferase, which transfers the methyl group to the second adenine in the DNA sequence GAATTC. The rate constant for conversion of the central complex (enzyme-DNA-S-adenosylmethionine) to products (enzyme-methylated DNA-S-adenosylhomocysteine) (...

Aim Paediatric inflammatory bowel disease (IBD) accounts for 7–22% of IBD cases globally and there is evidence to suggest that the incidence rising. 1 The aims therapy in paediatric are relieve symptoms, optimize growth, improve quality life while minimizing drug toxicity reducing risk complications without surgery. Treatment involves two main steps, inducing remission maintaining remission. Th...