PPAR expression was shown in both myeloid

PPARγ expression was shown in both myeloid and lymphoid leukemic cell lines. PPARγ activation with a natural ligand such as 15-deoxy-D12,14 – prostaglandin J2 or a synthetic ligand such as troglitazone results in inhibition of proliferation and induction of apoptosis. Assays demonstrated that apoptosis induction was mediated by caspase 3 activation. Besides, other apoptosis-related molecules remained unchanged at hour 24 of treatment while c-myc expression was significantly down-regulated (Yamakawa-Karakida et al., 2002).
In their study on promyelocytic cell line HL60, Hirase et al., demonstrated that TZD how to find the molarity of a solution leads to arrest at the G0/G1 phase and induced apoptosis, thus markedly suppressing proliferation (Hirase et al., 1999). In addition, again in a myelocytic cell leukemic line, significant apoptosis induction with BAX up-regulation of troglitazone and 15-deoxy-D12,14 – prostaglandin J2 and down-regulation of Bcl-2 and survival were also demonstrated (Liu et al., 2005).
Interestingly, PPARγ was shown to inhibit initiation of translation by inhibiting eukaryotic initiation factor-2 with phosphorylation at high concentrations independent of its ligand-mediated activation (Palakurthi et al., 2001).
Complete remission can be achieved in 90% of the patients with acute promyelocytic leukemia with ATRA treatment (Sanz et al., 2009). In ATRA-resistant patients and those with relapsing disease, however, use of arsenic trioxide and histone deacetylase inhibitors in addition to PPARγ agonists seems to be a treatment choice. Inhibition of PPARγ activity appears to contribute to cessation of differentiation in APL pathophysiology and, on the basis of this information, one may suggest that PPARγ activation with ligands results in differentiation of APL cells.
Glitazones were described by Isseman and Green in 1990 as molecules leading to gene transcription from nuclear receptors and resulting in peroxisome proliferation (Isseman and Green, 1990). The present study investigated whether rosiglitazone maleate, a synthetic ligand of PPARγ, was cytotoxic for HL-60, a myelocytic leukemic cell line. IC50 dose was at the 75μM concentration level. As a PPARγ agonist, rosiglitazone maleate was preferred since it has the highest binding affinity to the PPARγ receptor, i.e. lowest IC50, dose among other glitazones. PPARγ receptor binding affinity for rosiglitazone is ten times that of pioglitazone and 100 times that of troglitazone (Goldstein, 2002).
In previous studies with rosiglitazone maleate on the HL-60 cell line, the IC50 dose was not established and experiments were terminated at lower concentrations (Konopleva et al., 2004). Our experiments yielded an IC50 dose at higher concentrations compared to those described in the literature. Whether cells differentiate or undergo apoptosis will be established as the next step. This study obtained results which can provide guidance for future studies. This will enable a significant progress in the treatment of acute leukemia. Whether the PPARy agonist rosiglitazone maleate may provide additive effects in refractory or relapsing cases of acute leukemia may be set as an objective for the future studies.

Diabetes mellitus, a chronic metabolic disorder requires a significant amount of money for its management and thus puts considerable burden on healthcare services (Zimmet et al., 2001). Its prevalence is increasing worldwide at an alarming rate especially in low and middle income nations. The total number of diabetics is projected to rise from 285 million in 2010 to 438 million in 2030, while in developing countries the prevalence is projected to double between 2000 and 2030 (Shaw et al., 2010).
Sultanate of Oman is located in the Southeastern portion of the Arabian Peninsula. It has undergone tremendous socio-economic development over the past four decades but alongside diabetes has emerged as one of the most prevalent and growing health problems in the Sultanate of Oman that may be due to life style changes and obesity factor (Ministry of Health, 2003). Approximately 10% of the Omani population is currently living with diabetes and as per WHO estimates, number of diabetics in Oman will rise from 75,000 in 2000 to 217,000 in 2025 (Dunia et al., 2013). Patients of type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular and other secondary complications if the disease is not well controlled (Mooradian, 2003). Generally these patients experience a high incidence of morbidity and mortality as compared to non diabetics.