The aim of this study was to investigate the efficacy and safety of oral iron chelators, deferiprone in combination with desferrioxamine in comparison with desferrioxamine alone. A total of 70 transfusion-dependent thalassemia major patients were randomly selected to receive one of the following two treatments: deferiprone in combination with desferrioxamine (n=35, desferrioxamine+deferiprone group) or desferrioxamine alone (n=35, desferrioxamine-only group). Changes in serum ferritin, liver enzymes (alanine aminotransferase and aspartate aminotransferase), blood urea nitrogen, and creatinin were evaluated before the treatment and then six and 12 months after the treatment, and any side effect caused by iron chelators was reported during the study. Student’s t-test and repeated measures were used to compare different mean values for quantitative data and Chi-square to compare qualitative data.Serum ferritin decreased more significantly in patients on desferrioxamine+deferiprone therapy compared to patients who only received desferrioxamine (P<0.017). Side effects of deferiprone, including neutropenia, severe gastrointestinal upset, and arthropathy occurred in eight, four, and two patients, respectively but none led to discontinuation of the treatment. Beta-thalassemia major patients with iron overload due to transfusion could be successfully treated with a combination of desferrioxamine and deferiprone. This regimen is more effective than desferrioxamine-only therapy in decreasing serum ferritin; therefore, it also could be more effective in reducing iron overload and related complications in beta-thalessemia major patients.

Although successful iron chelation with deferiprone is associated with significant complications, patient’s compliance with medication regimens is of a high priority. The present study did evaluate the complications and compliance of domestically- manufactured deferiprone combined with desferrioxamine for iron chelation therapy. A total of 32 major beta thalassemic patients with cardiomyopathy were enrolled in the study and were monitored clinically and paraclinically. Upon every visit, the patients were prescribed only the number of tablets deemed necessary. The side effects observed as nausea (25%), vomiting (12%), neutropenia (12%), thrombocytopenia (6%), and joint pain (3%) without agranulocytosis or increased liver enzymes to more than twice the normal values. Deferiprone was discontinued in 30% of patients because of severe refractory gastrointestinal complaints (12%), recurrent neutropenia (6%), recurrent thrombocytopenia (6%), severe arthropathy (3%), or interferon therapy (3%). None of the patients, except one, remembered taking full number of the prescribed tablets. Twenty seven patients used 35% to 92% of the prescribed tablets. Poor compliance with deferiprone due to patient’s neglect to take the drug 3 times a day for a prolonged period was the main problem in this regimen. Although thrombocytopenia was more common compared with those of previous reports, other complications were seen with equal or lower frequencies.This study shows that a lower daily dose is the most favorable property of an oral iron chelator for prolonged usage.

ENCAPSULATION OF DRUGS INTO MULTIVESICULAR LIPOSOMES (DEPOFOAM) OFFERS A NOVEL APPROACH TO SUSTAINED RELEASE DRUG DELIVERY. DEPOFOAM -ENCAPSULATION HAS BEEN SHOWN TO RESULT IN SUSTAINED RELEASE LASTING OVER SEVERAL DAYS TO WEEKS AFTER NON-VASCULAR ADMINISTRATION. IN THIS PAPER WE DESCRIBE ENCAPSULATION OF DESFERRIOXAMINE IN A MULTIVESICULAR (MVL) DEPOT -DELIVERY SYSTEM. THE DEPOFOAM PARTICLES WERE CHARACTERIZED BY THEIR MORPHOLOGY, PARTICLE SIZE AND CAPTURE VOLUMES. THE EFFECTS OF VARIOUS CONCENTRATIONS OF COMPONENTS AND TWO MANUFACTURING METHODS ON CAPTURE VOLUMES OF THESE PARTICLES WERE STUDIED. THE LIGHT MICROGRAPH SHOWED THAT PARTICLES WERE SMOOTH AND MULTIVESICULAR WITHOUT ANY DEBRIS. THE PARTICLE SIZE OF THESE LIPOSOMES WAS BETWEEN 15-35 GM WITH CAPTURE VOLUMES ABOUT 27%. THE RESULTS SHOW THAT THE CONCENTRATION OF TRIOLEIN IN LIPID COMBINATION AND LYSINE IN THE SECOND AQUEOUS SOLUTION HAS SIGNIFICANT EFFECTS ON THE CAPTURED VOLUME. THE IN VITRO STUDIES IN 0.9% NACL AT 37 °C SHOWED THAT THE MULTIVESICULAR LIPOSOMES RELEASED DESFERRIOXAMINE SLOWLY OVER SEVERAL DAYS, AND 57% DESFERRIOXAMINE WAS RELEASED IN 9 DAYS.  

Back ground: Beta thalassemia major (BTM) is the most common genetic anemia that because of the chronic hemolyzation, needs to inject blood frequently. In these patients desferrioxamine (DFO) is used to decrease the iron in blood. One of the complications of DFO is sensorineural hearing loss (SNHL). This research is to determine hearing loss in BTM. Materials and Methods: In this analytic-descriptive research, all of the patients referring to Thalassemic Center of Yazd province between 2009-2010 were surveyed .Patients were evaluated with audiometry (HL=Hearing threshold ³ 20 dBHL), tympanometry .Exclusion criteria were: cases with ototoxic medications except DFO, past history of ear operation (myringotomy, ventilation tube, …) , the other diseases which affect hearing, abnormal physical exam (chronic otitis ,TM perforation,… ). 73 patients (35 female and 38 male) aged 6-40 years (mean 15/13 years) were enrolled. Variables include age, sex, and dosage and time consumption. Data were collected and analyzed with SPSS software. Results: Out of 73 cases (146 ears), 63/01 % (46 people) had hearing loss (which 86/95% was SNHL). In tympanometry test, 91/8 % of ears had type AN. There was statically significant difference between hearing loss (HL) and dosage of DFO in frequency of 2000 Hz and also significant difference between HL and time consumption in frequency of 250 Hz. In high frequency (8000 Hz) in both ears, HL had significant difference. There was statically significant difference between Sexes (males more than females show HL). In cases with age more than 14 years, HL had significant difference in frequencies of 250, 500, 4000 Hz in compare to people whose age was lower than 14 years. Discussion: In this study, the findings are indicative of DFO’s contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized .Time consumption and dosage of DFO should be control to prevent or reverse HL.

Siderophores are of important factors influencing bioavailability and fate of heavy metals in the arid and semi-arid soils. They are low molecular weight organic ligands excreted by aerobic soil microorganisms and some plants roots to acquire Fe. Siderophores may also complex other metals such as Pb .The main objective of this study was to investigate the effects of DFOB-siderophore on sorption of Pb on montmorillonite. The sorption of Pb on montmorillonite was studied as a function of pH (sorption envelopes) and as a function of Pb concentration (sorption isotherms) in the presence of siderophore using a 24-h batch equilibration experiment.The results of sorption envelopes showed that the siderophore increased sorption of Pb onto montmorillonite in all solution pH, specially at pH ³5. The results of equilibrium test (isotherms) revealed that removal of Pb from solution was not affected by siderophore at pH=4.5, while the siderophore strongly influenced the isotherm shape and increased Pb sorption onto montmorillonite at pH=6.5. The equilibrium data is best described by a Freundlich isotherm, in which the values obtained for the KF constant were 4.8 and 196.5 and for n constant were 0.8 and 2.1 in the absence and presence of the siderophore, respectively. These values are indication of high sorption affinity of Pb on montmorillonite in the presence of the siderophore.

Background and Aim: Thalassemia is one of the most prevalent heamoglobinopathies in the world in particular in Iran. Major thalassemia patients need blood transfusion and desferrioxamin injections throughout their life. Regarding improved life quality of thalassemic patients, new clinical problems, such as hearing loss, need more attention. This study was done to determine the frequency of hearing loss and otolaryngeal disorders together with their related factors in major beta thalassemic patients.Material and Methods: This was a descriptive analytic study and 84 beta thalassemia patients were examined and evaluated for hearing loss by an otolaryngologist. Standard pure tone audiometry was performed for the patients. Serum ferritin level was measured. Considering blood transfusion the patients were divided into two groups: those with suitable transfusions and those with unsuitable transfusions. Also in regard to desferrioxamin injections again the patients were divided into two groups: those with regular injections and those with irregular injections.Results: Among 84 beta thalassemic patients (40 M, 44 F) with mean age of 12.8±5.7 years, 10 (11.9%) had sensorineural hearing loss, 8 (9.5%) had conductive hearing loss, while 8 (9.5%) showed mixed hearing loss. There was no relationship between hearing loss and age, sex, ferritin level, but hearing loss had a significant relationship with doses and duration of desferrioxamine therapy (P<0.01). Also hearing loss had no significant relationship with regular and irregular blood transfusions and desferrioxamine injections (P<0.01).Conclusion: The results of this study implicated that high dose desferrioxamine was the main factor in the pathogenesis of ototoxicity in thalassemic patients. For management of these patients it is necessary to use proper doses of desferoxamine. Also blood transfusions should be proportional to body iron burden and hemoglobin. In addition, regular periodic otolaryngologic and audiometric follow up examinations are required for early diagnosis of hearing disorders in prevention of permanent hearing loss.

Introduction: The best and effective iron chelation remain one of the major strategy in clinical management of thalassemia major patients. The purpose of this study was to evaluate the safety and effectiveness of combined therapy with Desferrioxamine and Deferiprone in patients with thalassemia major that undergoing in regular administration of adequate desferrioxamine (5-6 days/week).Patients and Methods: This study was performed in two groups: one group with combination therapy, that had received oral deferiprone 70 mg/kg /day for 6 days and two days desferrioxamine 40 mg/kg with subcutaneous injection. Other group treated with only desferrioxamine with doses of 40 mg/kg 5- 6 day/week resemble to one year ago. (In past year both groups had regular & adequate administration and consumption of desferrioxamine with doses of 40 mg/kg 5-6 day/week).Thirty six patients were entered in this study. The efficacy of combined therapy was evaluated in 19 patients that treated with Desferrioxamine and deferiprone and 17 patients that treated with Desferal alone for at least 12 month. In both group the patients were received Desferal in Regular program in one year ago until to start of this study. Age of the patients was over 10 years old. Deferiprone administered orally 70 mg/kg/day in three divided dose and desferrioxamine 40 mg/kg/day by subcutaneus infusion overnight for 8-12 hr twice weekly. Serum ferritin concentrations were measured at base, 6 and 12 month. Full blood count were performed every 15 day for 2 first months and then monthly. The evaluation of cardiac function was performed in regular manner (every 6 months) and all of patients had normal cardiac function.Results: The mean decreased of ferritin level was 493 mg/L in combination therapy and mean increased in ferritin level was 637.6 mg/L in desferrioxamine group.Statistical analysis was performed with using T-test, and Paired T-test. There were significant differences between the two groups (p-value= 0.0001).The most common side effects in combined therapy group were dyspepsia and nausea in 6 patients (18.1%), especially in the first month of treatment. Joint pain and stiffness were observed in 4 cases (13.6%). Significant neutropenia and agranulocytosis were not observed.The serum ferritin level was increased in 64.7 % of patients that treated with desferrioxamine alone.Conclusion: The results of this study confirmed that the thalassemia major patients with iron overloaded whom received desferrioxamine as a regular manner (at least 40 mg/kg for 5 days /week) can be safety treated with a combination of deferiprone and desferrioxamine. This combination therapy was effective in reducing iron burden, as assessed by serum ferritin level.