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  1. Shafie AA, Wong JHY, Ibrahim HM, Mohammed NS, Chhabra IK
    Orphanet J Rare Dis, 2021 04 07;16(1):157.
    PMID: 33827621 DOI: 10.1186/s13023-021-01791-8
    BACKGROUND: Transfusion-dependent thalassaemia (TDT) is a hereditary blood disorder in which blood transfusion is the mainstay treatment to prolong survival and improve quality of life. Patients with this disease require blood transfusion at more than 100 ml/kg annually and iron-chelating therapy (ICT) to prevent iron overload (IOL) complications. There are substantial numbers of TDT patients in Malaysia, but limited data are available regarding the economic burden associated with this disease. The purpose of this study was to determine the lifetime cost of TDT from a societal perspective and identify potential factors increasing patient and family expenditures among thalassaemia populations.

    METHODS: The total lifetime cost per TDT patient (TC1) is the sum of lifetime healthcare cost (TC2) and lifetime patient and family healthcare expenditure (TC3). TC2 was simulated using the Markov model, taking into account all costs subsidized by the government, and TC3 was estimated through a cross-sectional health survey approach. A survey was performed using a two-stage sampling method in 13 thalassaemia centres covering all regions in Malaysia.

    RESULTS: A TDT patient is expected to incur TC2 of USD 561,208. ICT was the main driver of cost and accounted for 56.9% of the total cost followed by blood transfusion cost at 13.1%. TC3 was estimated to be USD 45,458. Therefore, the estimated TC1 of a TDT patient was USD 606,665. Sensitivity analyses showed that if all patients were prescribed oral ICT deferasirox for their lifetime, the total healthcare cost would increase by approximately 65%. Frequency of visits to health facilities for blood transfusion/routine monitoring and patients who were prescribed desferrioxamine were observed to be factors affecting patient and family monthly expenses.

    CONCLUSION: The lifetime cost per TDT patient was USD 606,665, and this result may be useful for national health allocation planning. An estimation of the economic burden will provide additional information to decision makers on implementing prevention interventions to reduce the number of new births and medical service reimbursement.

    Matched MeSH terms: Deferoxamine*
  2. Atas B, Caksen H, Tuncer O, Oner AF, Kirimi E, Akbayram S
    Med J Malaysia, 2005 Mar;60(1):91-3.
    PMID: 16250288
    In this article, we present an 18-month-old girl with acute iron poisoning who died from acute respiratory distress syndrome due to overdose of desferrioxamine. Our purpose is to emphasize the importance of close follow-up children with acute iron poisoning for desferrioxamine toxicity.
    Matched MeSH terms: Deferoxamine/poisoning*
  3. Dahlui, M., Hishamshah, M.I., Rahman, A.J. A, Shamsuddin, K., Aljunid, S.M.
    MyJurnal
    A cost-utility analysis was performed desferrioxamine treatment in thalctssaemia patients at two tertiary hospitals in Malaysia in 2004. A hundred and twelve transfusion dependent thalassaemia patients were grouped according to the status of desferrioxamine; optimum and sulwptimum. Cost analysis was from a patient and hospital perspectives while Quality Adjusted Life Years (QALYs) was the health outcome of choice. Incremental Cost·Effectiveness Ratio (ICER) was also stipulated to show the difference in cost for an additional QALY if patient currently on suboptimum desferrioxamine to switch using optimum desferrioxamine. Results on cost analysis showed the mean cost of treatment for thalassaemia patients on optimum desferrioxamirie was higher than those on sub·optimum desferrioxamine; (RM14, 775.00+SDRM4,737.00 and RM10,780+RM3,655, respectively). QALYs were 19.186+6.591 and 9.859+5275 in the optimum and suboptirnum group, respectively. Costutility analysis showed the cost per QALYs in optimum desferrioxamine group was RM59,045.00 compared to RM44,665.00 in suboptimum desferrioxamine group. ICER of patients on sub-optimum desferrioxamine switching to optimum desferrioxarnine was only RM420.39. Sensitivity analysis showed that the results were robust in the best and worst scenarios. In conclusion, although it is expensive for thalassaemia patients to use optimum desferrioxamine compared to sub-optimum desferrioxamine, the cost per QALYs gained was undoubtedly low.
    Matched MeSH terms: Deferoxamine
  4. Nithyapriya S, Sundaram L, Eswaran SUD, Perveen K, Alshaikh NA, Sayyed RZ, et al.
    Microb Ecol, 2024 Apr 17;87(1):60.
    PMID: 38630182 DOI: 10.1007/s00248-024-02377-0
    Microorganisms produce siderophores, which are low-molecular-weight iron chelators when iron availability is limited. The present analyzed the role of LNPF1 as multifarious PGPR for improving growth parameters and nutrient content in peanut and soil nutrients. Such multifarious PGPR strains can be used as effective bioinoculants for peanut farming. In this work, rhizosphere bacteria from Zea mays and Arachis hypogaea plants in the Salem area of Tamil Nadu, India, were isolated and tested for biochemical attributes and characteristics that stimulate plant growth, such as the production of hydrogen cyanide, ammonia (6 µg/mL), indole acetic acid (76.35 µg/mL), and solubilizing phosphate (520 µg/mL). The 16S rRNA gene sequences identified the isolate LNPF1 as Pseudomonas fluorescens with a similarity percentage of 99% with Pseudomonas sp. Isolate LNPF1 was evaluated for the production of siderophore. Siderophore-rich supernatant using a Sep Pack C18 column and Amberlite-400 Resin Column (λmax 264) produced 298 mg/L and 50 mg/L of siderophore, respectively. The characterization of purified siderophore by TLC, HPLC, FTIR, and 2D-NMR analysis identified the compound as desferrioxamine, a hydroxamate siderophore. A pot culture experiment determined the potential of LNPF1 to improve iron and oil content and photosynthetic pigments in Arachis hypogaea L. and improve soil nutrient content. Inoculation of A. hypogea seeds with LNPF1 improved plant growth parameters such as leaf length (60%), shoot length (22%), root length (54.68%), fresh weight (47.28%), dry weight (37%), and number of nuts (66.66) compared to the control (untreated seeds). This inoculation also improved leaf iron content (43.42), short iron content (38.38%), seed iron (46.72%), seed oil (31.68%), carotenoid (64.40%), and total chlorophyll content (98.%) compared to control (untreated seeds). Bacterized seeds showed a substantial increase in nodulation (61.65%) and weight of individual nodules (95.97) vis-à-vis control. The results of the present study indicated that P. fluorescens might be utilized as a potential bioinoculant to improve growth, iron content, oil content, number of nuts and nodules of Arachishypogaea L., and enrich soil nutrients.
    Matched MeSH terms: Deferoxamine
  5. Lee WJ, Mohd Tahir NA, Chun GY, Li SC
    Health Qual Life Outcomes, 2024 Feb 02;22(1):14.
    PMID: 38302961 DOI: 10.1186/s12955-023-02221-y
    Understanding consequences of poor chelation compliance is crucial given the enormous burden of post-transfusional iron overload complications. We systematically reviewed iron-chelation therapy (ICT) compliance, and the relationship between compliance with health outcome and health-related quality of life (HRQoL) in thalassaemia patients. Several reviewers performed systematic search strategy of literature through PubMed, Scopus, and EBSCOhost. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed. Of 4917 studies, 20 publications were included. The ICT compliance rate ranges from 20.93 to 75.3%. It also varied per agent, ranging from 48.84 to 85.1% for desferioxamine, 87.2-92.2% for deferiprone and 90-100% for deferasirox. Majority of studies (N = 10/11, 90.91%) demonstrated significantly negative correlation between compliance and serum ferritin, while numerous studies revealed poor ICT compliance linked with increased risk of liver disease (N = 4/7, 57.14%) and cardiac disease (N = 6/8, 75%), endocrinologic morbidity (N = 4/5, 90%), and lower HRQoL (N = 4/6, 66.67%). Inadequate compliance to ICT therapy is common. Higher compliance is correlated with lower serum ferritin, lower risk of complications, and higher HRQoL. These findings should be interpreted with caution given the few numbers of evidence.
    Matched MeSH terms: Deferoxamine/therapeutic use
  6. Balveer K, Pyar K, Wonke B
    Med J Malaysia, 2000 Dec;55(4):493-7.
    PMID: 11221163
    Thalassaemics in Malaysia are poorly chelated because desferrioxamine is too expensive and cumbersome for long term compliance. The efficacy and tolerability of the oral chelator deferiprone, and the effects of using a combination therapy in our patients were studied. Ten patients completed the study and the mean serum ferritin reduced from 7066.11 ug/L (2577-12,896 ug/L) to 3242.24 ug/L (955-6120 ug/L). The liver iron concentration did not show a significant drop (19.6 vs 18.2 mg/g dry weight) although 3 patients showed reductions ranging from 30-40%. Concomitant use of desferrioxamine increased the urinary excretion from a mean of 13.66 mg/day to 27.38 mg/day. Main side effects seen were nausea and rashes.
    Matched MeSH terms: Deferoxamine/administration & dosage*; Deferoxamine/therapeutic use
  7. Kong MH, Goh BS, Hamidah A, Zarina AL
    Med J Malaysia, 2014 Feb;69(1):9-12.
    PMID: 24814621 MyJurnal
    OBJECTIVE: This study aimed to evaluate the prevalence of sensorineural hearing loss (SNHL) in β-thalassaemia patients treated with Desferrioxamine (DFO) and determine the correlation of SNHL with average daily DFO dosage, serum ferritin level and Therapeutic index (T.I).

    METHODS: This is a cross sectional descriptive study carried out for a period of 14 months and 54 patients were recruited. The recruited patients are transfusion dependant β- thalassaemia patient aged 3 years and above treated with DFO. An interview, clinical examination and hearing assessment, which included tympanogram, and Pure Tone Audiometry (PTA) or behaviour alaudiometry were performed. The data on age started on DFO, average daily DFO, duration of DFO intake, serum ferritin past 1 year and Therapeutic Index (T.I) were obtained from patients' case notes.

    RESULTS: The prevalence of SNHL was 57.4% and majority has mild hearing loss (93.6%). Fourteen patients (25.9%) have bilateral ear involvement and as many as 17 patients (31.5%) have SNHL in either ear. A total of 23 patients (42.6%) have normal hearing level. Although the prevalence of SNHL was 57.4%, only a small percentage of the patient noticed and complained of hearing loss (11.1%). There is no association between age started on DFO, average daily DFO and duration of DFO intake with normal hearing group and those patients with SNHL. Positive correlation was seen between average daily DFO with 2000 and 4000Hz on PTA in the left ear and between serum ferritin level past 1 year with 4000 and 8000Hz in the right ear and 8000Hz in the left ear. No significant correlation was seen between T.I on PTA.

    CONCLUSION: The prevalence of SNHL from hearing assessment is high in β-thalassaemia patients in this study. However, it is manifested clinically in a smaller percentage. We suggest a baseline hearing assessment should be carried on all β-thalassaemia patients prior to DFO chelation therapy.
    Matched MeSH terms: Deferoxamine
  8. Nouri F, Salehinejad P, Nematollahi-Mahani SN, Kamarul T, Zarrindast MR, Sharifi AM
    Cell Mol Neurobiol, 2016 Jul;36(5):689-700.
    PMID: 26242172 DOI: 10.1007/s10571-015-0249-8
    Transplantation of neural-like cells is considered as a promising therapeutic strategy developed for neurodegenerative disease in particular for ischemic stroke. Since cell survival is a major concern following cell implantation, a number of studies have underlined the protective effects of preconditioning with hypoxia or hypoxia mimetic pharmacological agents such as deferoxamine (DFO), induced by activation of hypoxia inducible factor-1 (HIF-1) and its target genes. The present study has investigated the effects of DFO preconditioning on some factors involved in cell survival, angiogenesis, and neurogenesis of neural-like cells derived from human Wharton's jelly mesenchymal stem cells (HWJ-MSCs) in presence of hydrogen peroxide (H2O2). HWJ-MSCs were differentiated toward neural-like cells for 14 days and neural cell markers were identified using immunocytochemistry. HWJ-MSC-derived neural-like cells were then treated with 100 µM DFO, as a known hypoxia mimetic agent for 48 h. mRNA and protein expression of HIF-1 target genes including brain-derived neurotrophic factors (BDNF) and vascular endothelial growth factor (VEGF) significantly increased using RT-PCR and Western blotting which were reversed by HIF-1α inhibitor, while, gene expression of Akt-1, Bcl-2, and Bax did not change significantly but pAkt-1 was up-regulated as compared to poor DFO group. However, addition of H2O2 to DFO-treated cells resulted in higher resistance to H2O2-induced cell death. Western blotting analysis also showed significant up-regulation of HIF-1α, BDNF, VEGF, and pAkt-1, and decrease of Bax/Bcl-2 ratio as compared to poor DFO. These results may suggest that DFO preconditioning of HWJ-MSC-derived neural-like cells improves their tolerance and therapeutic potential and might be considered as a valuable strategy to improve cell therapy.
    Matched MeSH terms: Deferoxamine/pharmacology*
  9. Dahlui M, Hishamshah MI, Rahman AJ, Aljunid SM
    Singapore Med J, 2009 Aug;50(8):794-9.
    PMID: 19710979
    The quality of life of transfusion-dependent thalassaemia patients is affected by the disease itself and iron overload complications from repeated blood transfusion. Desferrioxamine has been used to remove the excess iron, resulting in decreased mortality and morbidity. In Malaysia, a significant proportion of the transfusion-dependent thalassaemia patients are not prescribed desferrioxamine, due to its high cost, especially as it is not subsidized by the government. The aim of this study was to measure the quality of life of thalassaemia patients on desferrioxamine treatment.
    Matched MeSH terms: Deferoxamine/therapeutic use*
  10. Kuppusamy UR, Tan JA
    West Indian Med J, 2011 Jan;60(1):3-8.
    PMID: 21809703
    Beta-thalassaemia major causes severe anaemia and patients with it may be transfusion-dependent for life. Regular blood transfusions cause iron-overload that leads to oxidative damage which can hasten mortality. The objective of this research was to study the oxidant-antioxidant indices in beta-thalassaemia major patients at the University of Malaya Medical Centre (UMMC) who were on desferrioxamine-chelation or without chelation therapy. Blood was collected from 39 Chinese patients and 20 controls. Plasma and peripheral blood mononuclear cell lysates (PBMC) were extracted and biochemical tests to evaluate oxidative stress were performed. Oxidative stress was evident in these patients as advanced oxidized protein products (AOPP) and lipid hydroperoxides were elevated, whereas glutathione peroxidase activity and the ferric reducing antioxidant power (FRAP) were reduced. The catalase activity in the patients' PBMC was elevated, possibly as a compensatory mechanism for the reduced glutathione peroxidase activity in both red blood cells and PBMC. The lower FRAP and higher AOPP levels in the non-chelated patients compared with the chelated patients were indicative of a lower oxidative stress level in the chelated patients. The ferritin levels in the chelated and non-chelated patients were high and the mean levels of liver enzyme activities in the majority of patients were elevated regardless of chelation therapy. In conclusion, this study indicates that desferrioxamine chelation therapy does not normalize ferritin level but attenuates oxidative damage and improves total antioxidant level in Malaysian Chinese beta-thalassaemia major patients.
    Matched MeSH terms: Deferoxamine/therapeutic use*
  11. Lee WS, Toh TH, Chai PF, Soo TL
    J Paediatr Child Health, 2011 Aug;47(8):535-40.
    PMID: 21392144 DOI: 10.1111/j.1440-1754.2011.02017.x
    To analyse the self-reported degree of and factors influencing the compliance to desferrioxamine (DFO) therapy in children with transfusion-dependent thalassaemia major in Malaysia.
    Matched MeSH terms: Deferoxamine/therapeutic use*
  12. Taher AT, Origa R, Perrotta S, Kouraklis A, Ruffo GB, Kattamis A, et al.
    Health Qual Life Outcomes, 2018 Nov 19;16(1):216.
    PMID: 30453981 DOI: 10.1186/s12955-018-1041-5
    BACKGROUND: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal.

    METHODS: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary.

    RESULTS: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations.

    CONCLUSIONS: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications.

    TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.

    Matched MeSH terms: Deferoxamine/therapeutic use*
  13. Ser HL, Ab Mutalib NS, Yin WF, Chan KG, Goh BH, Lee LH
    Front Microbiol, 2015;6:1398.
    PMID: 26733951 DOI: 10.3389/fmicb.2015.01398
    Streptomyces pluripotens MUSC 137 was isolated from mangrove soil obtained from Tanjung Lumpur, Pahang, Malaysia. We investigated the phylogenetic, genomic, biochemical, and phenotypic characteristics of this strain. Uniquely adapted microorganisms from mangrove habitats have previously yielded compounds of biopharmaceutical interest. In order to examine the bioactivities possessed by the strain, fermentation extract was prepared through solvent extraction method prior to bioactivities screenings. Antioxidant activity was examined via DPPH assay while the cytotoxic effect was assessed by means of examining the activity of the extract against selected human cancer cell lines, namely colon cancer cells (HCT-116, Caco-2, SW480, and HT-29), breast cancer cell (MCF-7), lung cancer cell (A549), prostate cancer cell (DU145), and cervical cancer cell (Ca Ski). The results revealed MUSC 137 possesses significant antioxidant activity and demonstrates cytotoxic effect against several cancer cell lines tested. The results indicated MCF-7 cells were most susceptible to the extract with the lowest IC50 (61.33 ± 17.10 μg/mL), followed by HCT-116 and A549. Additionally, selective index (SI) showed that MUSC 137 extract was less toxic against normal cell lines when compared to MCF-7 and HCT-116 cells. The extract was further subjected to chemical analysis using GC-MS and revealed the presence of deferoxamine and pyrrolizidines related compounds which may account for the antioxidant and cytotoxic properties observed.
    Matched MeSH terms: Deferoxamine
  14. Elfira Cassandra Enderik, Syahrizal Azizi Shaharudin, Gan, Siaw Yun, Tan, Wei Chong, Adong, Arthur James, Ho, Jackie Chit Khong, et al.
    MyJurnal
    Introduction: Long-term survival in beta-thalassaemia major is strongly influenced by adherence to iron chelation therapy. Identifying factors that influence the compliance remains the first step in improving iron chelation therapy. Objective:Due to increase in number of non-compliance to iron chelation therapy for patients in Hospital Keningau, Keningau, Sabah, we aim to evaluate the compliance, identify the factors and assess disease knowledge of patients so that preventive measurement can be formulated. Methodology: This was a cross-sectional study conducted in Hospital Keningau by a combination of self-administered and interviewer-administered survey. The survey consists of 3 domains – knowledge assessment based on 10 items, identifying factors for non-compliance and compliance to treatment. Percentage of compliance was measured based on amount taken reported by patients over the intended therapy. Association between knowledge and compliance was measured using Pearson’s Chi Square. Results: A number of 52 patients completed the survey. The average age was 18 ± 4.77 years. The mean knowledge score was 6.15 out of 10. The percentage of compliance to desferrioxamine was 78.2 ± 30.2% while for deferiprone it was 72.4 ± 32.6%. There were no association between knowledge score and compliance to desferrioxamine (p = 0.893) and deferiprone (p = 0.874). Lazziness and pain were the main reasons for non-compliance chosen by patients on desferrioxamine ABSTRACTCompliance and Barriers of Beta-Thalassaemia Patients towards Iron Chelation Therapy in Hospital Keningau, SabahElfira Cassandra Enderik1*, Syahrizal Azizi bin Shaharudin1, Gan Siaw Yun1, Tan Wei Chong1, Arthur James Adong1, Jackie Ho Chit Khong1, Shamadevi Pasupathi1, Maggie Low May Yee1, Sivaraj Raman1Borneo Journal of Medical Sciences (BJMS), Special Issue, Volume 2, March 2019: 7 – 81 Pharmacy Department, Hospital Keningau, Keningau, Sabah, Malaysia* Corresponding author’s email: elfira_11@yahoo.comBorneo Journal of Medical SciencesBJMSKeywords:thalassaemia, compliance, knowledge, factor NMRR Research ID: NMRR-18-404-39581
    8Borneo Journal of Medical Sciences (BJMS),Special Issue, Volume 2, March 2019: 7 – 811 (3): 35 – 38(19.2%) while for deferiprone it was lazziness (23.1%) and side effects (19.2%). The poor compliance was reflected on the high average ferritin levels of respondents (7573 ± 5749). Conclusion: Even though most adolescents had knowledge about their disease, it did not affect patients’ compliance to therapy. Lazziness was the most prominent factor for non-compliance in adolescents in our study. This might be because iron chelation therapy is usually seen as a hindrance to independence. Thus in order to improve compliances, further study is needed to investigate the association between compliance and the affecting factors identified in our study.
    Matched MeSH terms: Deferoxamine
  15. Tracey Anastacia Jeckson, Sreenivas Patro Sisinthy, Neo Yun Ping
    MyJurnal
    Introduction: Diabetic foot ulcer (DFU) is the most distressing complication of diabetes mellitus and often associated with risk of non-traumatic lower extremity amputations. Available formulations and wound dressings for DFU treatment are unfortunately less effective both on controlling and healing DFU. Issues commonly found are associated with providing an optimum environment which facilitates healing process; moist environment, effective oxygen exchange, preventing infection, controlling exudate and also patients compliance. The challenge is therefore to develop a novel drug delivery which address this unmet medical need for better wound treatment of chronic and slow healing DFU. This study aimed to develop a biomaterial based nanofibrous wound dressing formulation containing deferoxamine (DFO), which reported as a potential therapeutic approach to improve wound healing. Deferoxamine regulates the expression and increase stability of hypoxia-inducible factor-1α (HIF-1 α), growthfactor that crucial in wound repair, and thus increase neovascularization. Preparation and characterization of chosen polymers; chitosan/ alginate/polyvinyl alcohol (PVA) for nanofiber formulation will be carried out. Such biodegradable polymer nanofiber is a great benefit for drug delivery owing to its high surface area to volume ratio and high porosity which creates ideal environment to aid in wound healing. Methods: Nanofibers loaded DFO will be fabricated by electrospinning
    method that utilizes electrostatic force to produce fine fibers from the polymeric solution. Results: Various polymers concentrations and ratios are investigated to obtain the desired fibers characteristics. The selected optimized DFO nanofibers will be studied for its efficacy in wound healing through in-vivo animal studies. Conclusion: The proposed formulation would be an ideal low cost novel wound dressing with improved healing potential for efficient treatment
    of diabetic foot ulcer.
    Matched MeSH terms: Deferoxamine
  16. Rahman Jamal
    MyJurnal
    The thalassaemias are the commonest single gene disorders amongst the inherited diseases. In Malaysia, there are an estimated 2200 transfusion dependent thalassaemia patients. With a carrier rate of 3-5%, 120-340 new cases of thalassaemia are expected to be born each year. The reference treatments for these patients are regular blood transfusions and iron chelation therapy. With optimal management, these patients are able to survive into the third or fourth decade of life and most importantly avoid the complications related to transfusions and iron overload. The use of desferal locally is still limited to only those who can afford i.e. about 30% of the cases. Treatment for some of the complications such as hepatitis C, diabetes mellitus, growth impairment and pubertal delay, are now available. Curative treatment approaches like bone marrow transplantation have now become standard treatment for eligible cases whilst cord blood transplantation may yet offer hope for those who are without compatible sibling donors. Research on globin gene therapy looks very promising but will probably take some time to deliver. Hb F switching is a very novel idea but so far the results are mainly anecdotal. Finally, the strive for optimal management of thalassaemia must come hand in hand with a prevention programme to achieve a reduction of new cases.
    Matched MeSH terms: Deferoxamine
  17. Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi MH, et al.
    Cell Prolif, 2015 Oct;48(5):532-49.
    PMID: 26332145 DOI: 10.1111/cpr.12209
    OBJECTIVES: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs').

    MATERIALS AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models.

    RESULTS: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments.

    CONCLUSION: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.

    Matched MeSH terms: Deferoxamine/pharmacology*
  18. Merlot AM, Shafie NH, Yu Y, Richardson V, Jansson PJ, Sahni S, et al.
    Biochem Pharmacol, 2016 06 01;109:27-47.
    PMID: 27059255 DOI: 10.1016/j.bcp.2016.04.001
    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment.
    Matched MeSH terms: Deferoxamine/pharmacology
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