AIM To investigate whether pharmacogenetic loci or metabolite concentrations explain clinical response or side effects to AZA. METHODS Patients with IBD were given 2 mg/kg of AZA without dose escalation or adjustment. Serial clinical response, thiopurine methyl transferase (TPMT) activity and thioguanine nucleotide (TGN) concentrations were measured over 6 months. All patients were genotyped ...

In recent years there has been an evolution in the systemic therapy of skin disease, in particular immunosuppressive agents, retinoids and, most lately, biological drugs and new classes of drugs for advanced skin cancer. Developments in drug monitoring include measurement of thiopurine methyl transferase enzyme activity before prescribing azathioprine, to screen for patients at risk of severe b...

The family Flaviviridae comprises positive-strand RNA viral pathogens of humans and livestock with few treatment options. We have previously shown that azathioprine (AZA) has in vitro activity against bovine viral diarrhea virus (BVDV). While the mechanism of inhibition is unknown, AZA and related thiopurine nucleoside analogues have been used as immunosuppressants for decades and both AZA meta...

Thiopurine drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat acute lymphoblastic leukemia of childhood. To test the hypothesis that variation in the expression of genes within the "thiopurine pathway" might influence 6-MP and 6-TG sensitivity, we generated basal gene expression profiles and IC(50) values for both of these thiopurine drugs using a model system cons...

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/AIMS The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. METHODS This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 an...

The methyl esters of carboxylic acids are characteristic olfactory volatile compounds for the sweet aroma of snake fruit, (Salacca edulis, Reinw) cv. Pondoh. Although methanol was not detected as a volatile constituent, the crude enzymes showed activity to synthesize the methyl esters in the presence of acyl-CoA and methanol. Therefore, the biosynthetic origin of methanol was investigated, resu...

The administration of the convulsant, L-methionine-dl-sulfoximine (MSO), increased histamine N-methyl transferase (E.C. 2.1.1.8) (HMT) activity in rat and mouse brain and, to a lesser extent, catechol-O-methyl transferase (E.C. 2.1.1.6) (COMT) activity in rat brain. The duration of this effect was shortened by co-administration of L-methionine. The increased HMT activity was seen in S or 7 rat ...