Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide.

All-trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all-trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients' relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all- retinoic acid.

All- retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion.

The Duffy null genotype is associated with a lower level of CCL2, leukocytes and neutrophil count but not with the clinical outcome of HTLV-1 infection.

Chemokines are important in the immune response against viral infections, and may play a role in human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis. Polymorphisms in the Duffy antigen receptor for chemokines (DARC), such as rs12075 (A>G; ) and rs281477 (-46T>C; GATA-1 box) may influence circulating concentrations of proinflammatory chemokines. We investigate whether Duffy genotypes influence the HTLV-1 proviral load (PVL) level, HTLV-1 infection outcome and chemokine concentrations in HTLV-1 asymptomatic carriers (AC=162), HAM/TSP patients (HAM=135) and seronegative individuals (SN=71).

Plasmatic proinflammatory chemokines levels are tricky markers to monitoring HTLV-1 carriers.

The human T-cell leukemia virus type 1 (HTLV-1) is present throughout the world and is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory conditions. The pathogenesis of HAM/TSP involves a chronic inflammatory response in central nervous system (CNS), with the presence of HTLV-1 infected cells and HTLV-1-specific CD8+ lymphocytes. Chemokines may have a role in the infiltration of these cells into the CNS.