Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene.

With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34(+) progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell growth by reducing levels of reactive oxygen species (ROS) generated in response to cytokines. Forced PRDX2 expression inhibited c-Myc-induced leukemogenesis in vivo on BM transplantation in mice. Taken together, epigenome-wide analyses of H3Ac in AML led to the identification of PRDX2 as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML.

Effect of Ethyl Acetate Extract of Melothria Perpusilla on Oral Glucose Tolerance Test in Albino Rats.

INTRODUCTION: Diabetes mellitus is a group of common metabolic disorders sharing the phenotype of hyperglycaemia. Certain disadvantages like side effects or less efficacy limit the optimal use of antidiabetic drugs. AIM: To evaluate the effect of Ethyl Acetate Extract of MelothriaPerpusilla (EAEMP) on oral glucose tolerance test in albino rats. MATERIALS AND METHODS: Six healthy albino rats weighing between 100-150 g were selected. The same set of six animals were used for the experiment throughout and successive tests were conducted after a drug wash out period of 10 days. Fasting blood glucose samples were measured using glucometer. A 2% gum acacia suspension {10 ml/kg per oral (p.o.)} was given in all six albino rats followed by the oral glucose load of 3g/kg. Glucose concentrations were estimated at one hour and two hour after the glucose load. Using the same set of animals, similar tests were repeated with the test dose of 250 mg/kg and 500 mg/kg of EAEMP and glibenclamide (0.5 mg/kg p.o.). In this experiment, glucose was given immediately at the dose of 3 g/kg p.o. after the treatments. Drug wash out period of 10 days was maintained in between the successive tests to avoid the interference of action of the drug with the other. The non parametric data were analysed by Kruskal Wallis test. RESULTS: EAEMP produced a significant increase in the oral glucose tolerance test when compared with control and standard. CONCLUSION: Treatment with Melothria perpusilla lowers the blood glucose level due to higher oral glucose tolerance possibly due to release of insulin from the pancreas.

Azathioprine in Chronic Recalcitrant Erythema Nodosum Leprosum: A Case Report.

Erythema Nodosum Leprosum (ENL) may have a chronic course which may be recalcitrant to treatment. Preferred treatment modalities are systemic corticosteroids and thalidomide. Azathioprine, methotrexate and cyclosporine are immunosuppressants which may also be used as a steroid sparing agent. We report the case of a 48-year-old male diagnosed as lepromatous leprosy that developed ENL after four months of Multibacillary Multi-Drug Therapy (MB-MDT). He was treated with oral prednisolone (1 mg/kg/day) which was gradually tapered upto a dose of 7.5 mg/day. He developed recurrences on and off once the dose reached the said level and this continued for three years. Oral clofazamine (300 mg/day x 6 months; then 100 mg/day x 6 months) was also added in the second year. Thalidomide (200 mg/day) was also given but withdrawn due to adverse effect after 10 days. Azathioprine was started at a dose of 100 mg/day following which there was resolution of symptoms by one week and no recurrences by 10 weeks; it was given for eight months after which the dose was tapered to 50 mg/day for another four months. Complete withdrawal of oral prednisolone after gradual tapering was possible by 12 months of azathioprine therapy. The patient is still on regular follow-up with no recurrences so far till the last check-up.