PRE-SCREENING TPMT STATUS OF LIVER TRANSPLANT PATIENTS FOR AZATHIOPRINE THERAPY–A SINGLE CENTRE EXPERIENCE FROM SOUTH INDIA

Objective: To assess azathioprine-induced bone marrow toxicity and its correlation with thiopurine methyltransferase (TPMT) mutation in liver transplant patients who develop myelosuppression while on azathioprine therapy.Methods: A prospective observational study was conducted from 1st September 2014 to 30thJune 2015 on 60 liver transplant patients who were tested for TPMT allele activity prior to receiving azathioprine. Haemoglobin levels, platelet counts and white blood cell counts of the patients were monitored for the occurrence of myelotoxicity. Patients who underwent liver transplant during the retrospective period from 1st September 2011 to 31st August 2014 and who developed myelosuppression while on azathioprine therapy were also tested for TPMT genotype.Results: A total of 76 liver transplant patients were tested for TPMT mutation. Prevalence of TPMT mutation in the study patients was 3.95%. The heterozygous TPMT*1/*3C genotype was traced in 2.63% of the patients while 1.32% of patients were homozygous for TPMT*3C allele. Interestingly 43.4% of patients with wild allele also showed azathioprine-induced myelosuppression. Azathioprine dose of 100 mg showed a higher degree of myelotoxicity than lower doses. Haematological indices of 42.1% of patients normalised on cessation of azathioprine therapy.Conclusion: Myelosuppression following the introduction of azathioprine was observed in patients with both ‘mutant' and ‘wild-type' alleles. Therefore a cautious approach has to be taken in pre-screening liver transplant recipients for TPMT allele determination in our population. The absence of TPMT mutation does not ensure freedom from myelosuppression. Hence regular monitoring of haematological indices of such patients receiving thiopurine therapy should be continued

New Insights into the Metabolic and Molecular Mechanism of Plant Response to Anaerobiosis

Under anaerobic conditions, plants apply a wide spectrumof precise adaptive strategies responding to several critical challenges. The ability of efficiently sensing the oxygen presence demonstrates the existence of both direct and indirect ways of perception. The subsequent coordinate metabolic reassessment is currently under study. The complex molecular response implicates not only transcriptional and translational regulation of specific genes but also posttranscriptional and posttranslational regulatory mechanisms, each and all integrating the metabolic settings. Furthermore, the accumulation of typical metabolites during low oxygen stress condition is a key factor that suggests some critical topics in the regulation of metabolic pathways. Here, we summarize the main routes for adaptive behavior during oxygen depletion, from oxygen availability perception to recently discovered molecular mechanisms and metabolic adaptations