Combination therapy - deferasirox and deferoxamine - in thalassemia major patients in emerging countries with limited resources.

BACKGROUND: The problem of iron-overload observed in thalassemia patients can be overcome using chelating agents such as deferiprone (Ferroprox(®) ), deferasirox (Exjade(®) ) and deferoxamine (Desferal(®) ). Although these drugs can be used as monotherapy, combined therapy, especially deferiprone with deferoxamine, has led to promising outcomes in various studies. METHODS AND MATERIALS: In this quasi-experimental study, serum ferritin levels were evaluated in 32 ß-thalassemia major patients with severe iron overload before and after receiving combined deferasirox (30-40 mg kg(-1) day(-1) ) and deferoxamine (40-50 mg kg(-1) day(-1) ) 2 days a week. This study was conducted from September 2012 to September 2013 in Southern Iran. RESULTS: The mean of serum ferritin levels significantly reduced from 4031 ± 1955 to 2416 ± 1653 ng mL(-1) after 12 months of therapy (P < 0·001). Echocardiograph findings showed significant improvement 1year after end of the study (P < 0·001). No drug toxicity was observed by monitoring serum creatinine, liver enzymes and blood urea nitrogen (BUN) during the study period. We observed no correlation between mean serum ferritin change and age (P = 0·87). In addition, the mean serum ferritin change did not differ between male and female thalassemia patients (P = 0·454). No difference in mean serum ferritin change was observed between patients who had undergone splenectomy compared to those who had not done so (P = 0·307). CONCLUSION: The study suggests that combination chelating therapy with deferasirox and deferoxamine can effectively reduce iron burden in ß-thalassemia major patients with heavy iron overload without any significant complications.

Molecular structure and biological studies on Cr(III), Mn(II) and Fe(III) complexes of heterocyclic carbohydrazone ligand.

The chelating behavior of the ligand (H2APC) based on carbohydrazone core modified with pyridine end towards Cr(III), Mn(II) and Fe(III) ions have been examined. The (1)H NMR and IR data for H2APC revealed the presence of two stereoisomers syn and anti in both solid state and in solution in addition to the tautomeric versatility based on the flexible nature of the hydrazone linkage leading to varied coordination modes. The spectroscopic data confirmed that the ligand behaves as a monobasic tridentate in Cr(III) and Fe(III) complexes and as neutral tetradentate in Mn(II) complex. The electronic spectra as well as the magnetic measurements confirmed the octahedral geometry for all complexes. The bond length and angles were evaluated by DFT method using material studio program for all complexes. The thermal behavior and the kinetic parameters of degradation were determined using Coats-Redfern and Horowitz-Metzger methods. The antioxidant (DDPH and ABTS methods), anti-hemolytic and cytotoxic activities of the compounds have been screened. Cr(III) complex and H2APC showed the highest antioxidant activity using ABTS and DPPH methods. With respect to in vitro Ehrlich ascites assay, H2APC exhibited the potent activity followed by Fe(III) and Cr(III)complexes.

Characterization and biological studies on Co(II), Ni(II) and Cu(II) complexes of carbohydrazones ending by pyridyl ring.

The chelating behavior of ligands based on carbohydrazone core modified with pyridine end towards Co(II), Ni(II) and Cu(II) ions have been examined. The ligands derived from the condensation of carbohydrazide with 2-acetylpyridine (H(2)APC) and 4-acetylpyridine (H(2)APEC). The (1)H NMR, IR data and the binding energy calculations of H(2)APC revealed the presence of two stereoisomers syn and anti in the solid state and in the solution. The (1)H NMR, IR data and the binding energy calculations confirmed the presence of H(2)APEC in one keto form only in the solid state and in the solution. The spectroscopic data confirmed that H(2)APC behaves as a monobasic pentadentate in Co(II) and Cu(II) complexes and as mononegative tetradentate in Ni(II) complex. On the other hand, H(2)APEC acts as a mononegative tridentate in Co(II) complex, neutral tridentate in Ni(II) complex and neutral bidentate in Cu(II) complex. The electronic spectra and the magnetic measurements of complexes as well as the ESR of the copper complexes suggested the octahedral geometry. The bond length and bond angles were evaluated by DFT method using material studio program. The thermal behavior and the kinetic parameters of degradation were determined using Coats-Redfern and Horowitz-Metzger methods. The antioxidant (DDPH and ABTS methods), anti-hemolytic and in vitro Ehrlich ascites of the compounds have been screened.

Evaluation of male-mediated reproductive toxic effects of methamidophos in the mouse.

The reproductive toxicity of the insecticide methamidophos was studied in male mice. Adult male mice were treated by gavage with methamidophos at doses of 0, 1, 2 and 3 mg kg(-1) day(-1) for 4 weeks before mating with untreated females. Brain and skeletal muscle acetylcholinesterase activity was inhibited in the middle- and high-treated groups. Methamidophos treatment was associated with a decreased number of live foetuses and an increased number of dead and resorption foetuses at 2 and 3 mg kg(-1) day(-1) treated groups. The per cent morphologically normal spermatozoa were affected in the 2 and 3 mg kg(-1) day(-1) dose groups; however, sperm motility and count were decreased in the same treated groups compared to the control. Histological examination of brain, muscles, testes and epididymis revealed histological abnormalities in a dose-dependent manner. The current study demonstrated adverse effects of male methamidophos exposure on pregnancy outcome with effects on sperm parameters at 2 and 3 mg kg(-1) day(-1) .