-
Internal Medicine (Tokyo, Japan) 2015
Topics: Aged; Anti-Inflammatory Agents; Deferoxamine; Humans; Male; Octreotide; Prednisolone; Sarcoidosis; Scalp; Tomography, Emission-Computed; Treatment Outcome
PubMed: 26521919
DOI: 10.2169/internalmedicine.54.5110 -
BioMed Research International 2015Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO,... (Review)
Review
Deferoxamine mesylate (DFO) is the most commonly used iron-chelating agent to treat transfusion-related hemosiderosis. Despite the clear advantages for the use of DFO, numerous DFO-related systemic toxicities have been reported in the literature, as well as sight-threatening ocular toxicity involving the retinal pigment epithelium (RPE). The damage to the RPE can lead to visual field defects, color-vision defects, abnormal electrophysiological tests, and permanent visual deterioration. The purpose of this review is to provide an updated summary of the ocular findings, including both functional and structural abnormalities, in DFO-treated patients. In particular, we pay particular attention to analyzing results of multimodal technologies for retinal imaging, which help ophthalmologists in the early diagnosis and correct management of DFO retinopathy. Fundus autofluorescence, for example, is not only useful for screening patients at high-risk of DFO retinopathy, but is also a prerequisite for identify specific high-risk patterns of RPE changes that are relevant for the prognosis of the disease. In addition, optical coherence tomography may have a clinical usefulness in detecting extent and location of different retinal changes in DFO retinopathy. Finally, this review wants to underline the need for universally approved guidelines for screening and followup of this particular disease.
Topics: Deferoxamine; Hemosiderosis; Humans; Iron Chelating Agents; Retina; Retinal Diseases; Retinal Vessels
PubMed: 26167477
DOI: 10.1155/2015/249617 -
Journal of Pediatric Hematology/oncology Apr 2019The researcher assessed the beliefs and adherence associated with both oral deferasirox and deferoxamine infusion chelation therapies among Jordanian children with... (Comparative Study)
Comparative Study
The researcher assessed the beliefs and adherence associated with both oral deferasirox and deferoxamine infusion chelation therapies among Jordanian children with thalassemia major, and compared the adherence levels between the recipients of each. In this descriptive cross-sectional study, 120 participants were recruited from 3 major thalassemia treatment clinics in Jordan using convenience sampling. Data were collected through questionnaires on demographic- and disease-related information, the beliefs about medicines, and a medication adherence report scale. Most participants showed a high adherence to deferoxamine infusion and oral deferasirox (87.20% and 89.08%, respectively), and believed in the necessity of deferoxamine for maintaining health (89.34%). However, 41.32% of the participants had strong concerns about deferoxamine use. While most participants believed in the need for oral deferasirox (89.84%), about 40.7% had strong concerns about its use. An independent samples t test showed no statistically significant difference in the adherence between the oral deferasirox and infusion deferoxamine recipients (t=1.048, DF=118, P=0.075). Jordanian children with thalassemia have positive beliefs and adherence to both oral and infusion chelation therapies. Health care providers should pay attention to patients' beliefs and discuss the major concerns pertaining to iron chelation therapy with them to enhance the continuity of adherence therapy.
Topics: Adolescent; Chelation Therapy; Child; Cross-Sectional Studies; Culture; Deferasirox; Deferoxamine; Female; Humans; Jordan; Male; Medication Adherence; Surveys and Questionnaires; beta-Thalassemia
PubMed: 30585946
DOI: 10.1097/MPH.0000000000001399 -
Neuroreport Nov 2022Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous...
BACKGROUND AND PURPOSE
Subarachnoid hemorrhage (SAH) is associated with sustained vasoconstriction in retinal vessels and vasoconstriction leads to retinal ischemia and hypoxia. Our previous finding also revealed the changes in hypoxia-related elements in the retina after SAH, further lending weight to the hypothesis that retinal vasospasm and hypoxia after SAH. Deferoxamine is a high-affinity iron chelator with reported neuroprotective effects against stroke. Here, we aimed to explore the effects of deferoxamine on retinal hypoxia after SAH.
METHODS
SAH was established and deferoxamine was injected intraperitoneally for 3 days in the treatment group. To detect retinal new vessels, platelet endothelial cell adhesion molecule (CD31) was labeled by immunofluorescence and immunohistochemistry. Furthermore, the effects of deferoxamine on the expression of vascular endothelial growth factor A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) were revealed by western blot analysis.
RESULTS
The immunofluorescence and immunohistochemical staining of CD31 revealed a marked increase in new vessels in the retinal ganglion cell layer after deferoxamine treatment. By western blot analysis, HIF-1α and VEGF-A increased gradually in the first day and then rebounded to a new level on day 7. A deferoxamine-induced increase in HIF-1α/VEGF-A expression was also confirmed by western blot.
CONCLUSIONS
Our findings suggest that modulating the application of deferoxamine may offer therapeutic approaches to alleviate retinal complications after SAH.
Topics: Animals; Cell Adhesion Molecules; Deferoxamine; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Iron Chelating Agents; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Retina; Subarachnoid Hemorrhage; Vascular Endothelial Growth Factor A
PubMed: 36165027
DOI: 10.1097/WNR.0000000000001835 -
Oxidative Medicine and Cellular... 2015The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart... (Review)
Review
The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies.
Topics: Animals; Cardiomyopathies; Deferoxamine; Disease Models, Animal; Humans; Iron; Iron Overload; Iron-Regulatory Proteins; Oxidative Stress; Reactive Oxygen Species; Siderophores
PubMed: 25878762
DOI: 10.1155/2015/230182 -
Molecular Imaging and Biology Dec 2023Site-specific approaches to bioconjugation produce well-defined and homogeneous immunoconjugates with potential for superior in vivo behavior compared to analogs...
PURPOSE
Site-specific approaches to bioconjugation produce well-defined and homogeneous immunoconjugates with potential for superior in vivo behavior compared to analogs synthesized using traditional, stochastic methods. The possibility of incorporating photoaffinity chemistry into a site-specific bioconjugation strategy is particularly enticing, as it could simplify and accelerate the preparation of homogeneous immunoconjugates for the clinic. In this investigation, we report the synthesis, in vitro characterization, and in vivo evaluation of a site-specifically modified, Zr-labeled radioimmunoconjugate created via the reaction between an mAb and an Fc-binding protein bearing a photoactivatable 4-benzoylphenylalanine residue.
PROCEDURES
A variant of the Fc-binding Z domain of protein A containing a photoactivatable, 4-benzoylphenylalanine residue - Z(35BPA) - was modified with desferrioxamine (DFO), combined with the A33 antigen-targeting mAb huA33, and irradiated with UV light. The resulting immunoconjugate - DFO-huA33 - was purified and characterized via SDS-PAGE, MALDI-ToF mass spectrometry, surface plasmon resonance, and flow cytometry. The radiolabeling of DFO-huA33 was optimized to produce [Zr]Zr-DFO-huA33, and the immunoreactivity of the radioimmunoconjugate was determined with SW1222 human colorectal cancer cells. Finally, the in vivo performance of [Zr]Zr-DFO-huA33 in mice bearing subcutaneous SW1222 xenografts was interrogated via PET imaging and biodistribution experiments and compared to that of a stochastically labeled control radioimmunoconjugate, [Zr]Zr-DFO-huA33.
RESULTS
HuA33 was site-specifically modified with Z(35BPA)-DFO, producing an immunoconjugate with on average 1 DFO/mAb, high in vitro stability, and high affinity for its target. [Zr]Zr-DFO-huA33 was synthesized in 95% radiochemical yield and exhibited a specific activity of 2 mCi/mg and an immunoreactive fraction of ~ 0.85. PET imaging and biodistribution experiments revealed that high concentrations of the radioimmunoconjugate accumulated in tumor tissue (i.e., ~ 40%ID/g at 120 h p.i.) but also that the Z(35BPA)-bearing immunoPET probe produced higher uptake in the liver, spleen, and kidneys than its stochastically modified cousin, [Zr]Zr-DFO-huA33.
CONCLUSIONS
Photoaffinity chemistry and an Fc-binding variant of the Z domain were successfully leveraged to create a novel site-specific strategy for the synthesis of radioimmunoconjugates. The probe synthesized using this method - DFO-huA33 - was well-defined and homogeneous, and the resulting radioimmunoconjugate ([Zr]Zr-DFO-huA33) boasted high specific activity, stability, and immunoreactivity. While the site-specifically modified radioimmunoconjugate produced high activity concentrations in tumor tissue, it also yielded higher uptake in healthy organs than a stochastically modified analog, suggesting that optimization of this system is necessary prior to clinical translation.
Topics: Humans; Animals; Mice; Immunoconjugates; Tissue Distribution; Positron-Emission Tomography; Neoplasms; Zirconium; Cell Line, Tumor; Deferoxamine
PubMed: 37052759
DOI: 10.1007/s11307-023-01818-5 -
Dermatologic Surgery : Official... Jul 2023Hair transplantation has become a popular choice for alopecia treatment; however, postsurgical hair shedding still annoys both patients and surgeons. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hair transplantation has become a popular choice for alopecia treatment; however, postsurgical hair shedding still annoys both patients and surgeons.
OBJECTIVE
To explore the impact of graft-holding solution on postsurgical hair shedding and testify the protective efficacy of histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine (HTK-AD).
METHODS
There were 240 patients enrolled in the study, and the follicles were placed into either HTK-AD or Ringer solution (RS). Masson staining and live/dead staining were performed to evaluate graft morphology and apoptosis levels, respectively. The between-group comparison of postsurgical graft shedding, survival rate, complications, and patient satisfaction was performed.
RESULTS
Grafts in HTK-AD maintained organized dense collagen construction and higher cell viability, but those preserved in RS became soft, which hindered implantation. Histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine significantly reduced the incidence of postsurgical hair shedding (73.81% vs 95%), delayed shedding onset, and diminished shedding amount versus RS ( p < .05) when ≥3,000 grafts were transplanted. The shedding duration was shortened, and hair regrowth started earlier in HTK-AD versus RS ( p < .05); thus, satisfaction was increased. The final survival rate showed no difference between 2 groups.
CONCLUSION
Histidine-tryptophan-ketoglutarate solution with adenosine triphosphate and deferoxamine is superior to RS for hair graft preservation because it improves graft viability and alleviates postsurgical shedding.
Topics: Humans; Organ Preservation Solutions; Organ Preservation; Adenosine; Deferoxamine; Adenosine Triphosphate
PubMed: 37036372
DOI: 10.1097/DSS.0000000000003799 -
Journal of Reconstructive Microsurgery Oct 2022Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as... (Review)
Review
BACKGROUND
Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as xerostomia, which requires frequent daily maintenance, to destructive degenerative processes such as osteoradionecrosis, which can contribute to flap failure and delay or reverse oral rehabilitation. Despite the need for effective radioprotectants, the literature remains sparse, primarily focused on interventions beyond the surgeon's control, such as maintenance of good oral hygiene or modulation of radiation dose.
METHODS
This narrative review aggregates and explores noninvasive, systemic treatment modalities for prevention or amelioration of radiation-associated soft tissue injury.
RESULTS
We highlighted nine modalities with the most clinical potential, which include amifostine, melatonin, palifermin, hyperbaric oxygen therapy, photobiomodulation, pentoxifylline-tocopherol-clodronate, pravastatin, transforming growth factor-β modulators, and deferoxamine, and reviewed the benefits and limitations of each modality. Unfortunately, none of these modalities are supported by strong evidence for prophylaxis against radiation-associated soft tissue injury.
CONCLUSION
While we cannot endorse any of these nine modalities for immediate clinical use, they may prove fruitful areas for further investigation.
Topics: Amifostine; Deferoxamine; Fibroblast Growth Factor 7; Humans; Melatonin; Pravastatin; Soft Tissue Injuries; Transforming Growth Factors
PubMed: 35213927
DOI: 10.1055/s-0042-1742731 -
Journal of Cerebral Blood Flow and... Feb 2020Intracerebral hemorrhage is associated with significant morbidity and mortality. Some clinical trials demonstrated a trend towards benefit with surgical evacuation of... (Review)
Review
Intracerebral hemorrhage is associated with significant morbidity and mortality. Some clinical trials demonstrated a trend towards benefit with surgical evacuation of intracerebral hemorrhage, without strong statistically significant results. Subsequent studies focused on minimally invasive techniques. Improved outcomes were more likely with surgical reduction of intracerebral hemorrhage volume to ≤15 mL. Deferoxamine is currently being evaluated as a therapeutic tool in intracerebral hemorrhage with promising results. There continues to be a lack of level I evidence supporting medical and surgical tools for intracerebral hemorrhage evacuation. Could a combination of minimally invasive surgery with hematoma lysis and Deferoxamine result in more effective hematoma evacuation?
Topics: Clinical Trials as Topic; Deferoxamine; Female; Humans; Intracranial Hemorrhages; Male; Minimally Invasive Surgical Procedures
PubMed: 31791162
DOI: 10.1177/0271678X19892660 -
Plastic and Reconstructive Surgery Mar 2018Radiation therapy is a mainstay in the treatment of many malignancies, but collateral damage to surrounding tissue, with resultant hypovascularity, fibrosis, and...
BACKGROUND
Radiation therapy is a mainstay in the treatment of many malignancies, but collateral damage to surrounding tissue, with resultant hypovascularity, fibrosis, and atrophy, can be difficult to reconstruct. Fat grafting has been shown to improve the quality of irradiated skin, but volume retention of the graft is significantly decreased. Deferoxamine is a U.S. Food and Drug Administration-approved iron-chelating medication for acute iron intoxication and chronic iron overload that has also been shown to increase angiogenesis. The present study evaluates the effects of deferoxamine treatment on irradiated skin and subsequent fat graft volume retention.
METHODS
Mice underwent irradiation to the scalp followed by treatment with deferoxamine or saline and perfusion and were analyzed using laser Doppler analysis. Human fat grafts were then placed beneath the scalp and retention was also followed up to 8 weeks radiographically. Finally, histologic evaluation of overlying skin was performed to evaluate the effects of deferoxamine preconditioning.
RESULTS
Treatment with deferoxamine resulted in significantly increased perfusion, as demonstrated by laser Doppler analysis and CD31 immunofluorescent staining (p < 0.05). Increased dermal thickness and collagen content secondary to irradiation, however, were not affected by deferoxamine (p > 0.05). Importantly, fat graft volume retention was significantly increased when the irradiated recipient site was preconditioned with deferoxamine (p < 0.05).
CONCLUSIONS
The authors' results demonstrated increased perfusion with deferoxamine treatment, which was also associated with improved fat graft volume retention. Preconditioning with deferoxamine may thus enhance fat graft outcomes for soft-tissue reconstruction following radiation therapy.
Topics: Adipose Tissue; Animals; Deferoxamine; Female; Graft Survival; Healthy Volunteers; Humans; Male; Mice, SCID; Middle Aged; Radiation-Protective Agents; Scalp; Surgical Flaps
PubMed: 29135894
DOI: 10.1097/PRS.0000000000004167