Mtimp

(6-methyl-TIMP)

Fig. 2 The metabolic pathway of TPMT action. (View this art in color at www.dekker.com.)

with decreased TPMT enzyme activity and increased risk of treatment.[7] However, adverse drug reactions, such as hepatic toxicity, cannot be linked to TPMT polymorphisms and activity. Some TPMT variant alleles, which are associated with low enzyme activity, are known.[8-12] In Caucasians (55-70%), however, TPMT*3A is the most common variant allele attributed to low TPMT activi-ty.[13] TPMT*3C is more common among Asians compared to Caucasians, where this variant is quite rare (<1%). The wild-type TPMT gene is associated with higher TPMT activity, and heterozygosity or homozy-gosity for one variant allele show significantly reduced enzyme activity.[14-16] It has to be considered that molecular testing, which has to be performed prior to therapy, might vary from one ethnic group to another, and still be unable to provide 100% safety. Some still unknown mutations might also be responsible for decreased TPMT activity.[17] Thus TPMT phenotyping is being performed in various establishments. The enzyme activity of erythrocytes correlates well with the activity of bone marrow cells and might therefore be measured prior to therapy. However, significant variability of enzyme activities in wild-type patients are known and cannot yet be clearly linked to genetic patterns. Even in TPMT heterozygotes, an increased risk of thiopurine hematopoietic toxicity was observed by Relling et al.[18] Individual dosing of 6-MP might help to successfully treat ALL, and therefore the aim is to find all genetic variants that are linked to altered TPMT activity. In such a way, genotyping might help to determine the individual dose needed for effective cancer chemotherapy.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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