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1.
J Int Med Res ; 49(1): 300060520987396, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33478296

RESUMO

OBJECTIVE: This study evaluated serum ferritin (SF) levels and investigated their relationships with various clinical markers in patients with multiple myeloma (MM). Furthermore, the effects and molecular mechanism of deferoxamine (DFO) in myeloma cells were studied. METHODS: Clinical data from 84 patients with MM were collected to evaluate SF content and its relationship with several important clinical parameters. MM1S and MM1R myeloma cells were chosen to investigate the effects of iron and DFO on cell survival and apoptosis. RESULTS: Increased SF levels were detected in newly diagnosed patients, especially those with stage III disease or the κ isotype. SF content was positively correlated with ß2-microglobulin, interleukin-6, and lactate dehydrogenase expression. Furthermore, patients with progressive or relapsed disease had higher SF levels. Importantly, iron chelation with DFO efficiently inhibited myeloma cell survival and accelerated apoptosis by regulating apoptosis-related genes. CONCLUSIONS: The importance of SF for MM was highlighted. Additionally, it is suggested that DFO may be a good therapeutic option for MM.


Assuntos
Desferroxamina , Mieloma Múltiplo , Sobrevivência Celular , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Humanos , Ferro , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico
2.
Ann Hematol ; 99(10): 2289-2294, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737633

RESUMO

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Terapia por Quelação/métodos , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/terapia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Transfusão de Sangue , Deferiprona/administração & dosagem , Desferroxamina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/etiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Talassemia/complicações , Reação Transfusional , Resultado do Tratamento , Função Ventricular Esquerda
5.
World Neurosurg ; 137: e9-e17, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31518742

RESUMO

BACKGROUND: With little information available on axonal and myelin damage surrounding the contusion, the study of spinal cord injury (SCI) so far has focused on neuronal death. In this study, we investigated the role of iron overload in long-term oligodendroglia death and progressive white matter damage to rats after SCI using the iron chelator, deferoxamine (DFX). METHODS: Female Sprague-Dawley rats received either a contusion at T10 or sham-surgery. The rats were treated with DFX or vehicle. All rats were evaluated in behavioral assessments and then euthanized at different time points. Spinal cords were analyzed by diaminobenzidine-enhanced Perls' staining, non-heme iron measurements, Western blotting, immunohistochemistry, and transmission electron microscopy. RESULTS: Iron accumulation after SCI resulted in the upregulation of transferrin receptor and divalent metal transporter 1, which exacerbated the intracellular iron overload. DFX treatment reduced iron overload-induced delayed oligodendrocyte death (e.g., 21 days: 47.12 ± 10.5 vs. 20.02 ± 9.4 x 103/mm2 in the vehicle-treated group, n = 4, P < 0.05). After SCI, the markers of axonal damage and demyelination were increased in white matter in the vehicle-treated group compared with the DFX-treated group (P < 0.05). CONCLUSIONS: Iron overload plays an important role in progressive white matter damage after SCI. DFX may be an effective treatment for white matter damage after SCI.


Assuntos
Desferroxamina/uso terapêutico , Oligodendroglia/efeitos dos fármacos , Sideróforos/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Substância Branca/efeitos dos fármacos , Animais , Desferroxamina/farmacologia , Modelos Animais de Doenças , Feminino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Ratos , Ratos Sprague-Dawley , Receptores da Transferrina/metabolismo , Sideróforos/farmacologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Substância Branca/metabolismo , Substância Branca/patologia
7.
J Surg Res ; 246: 419-426, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31630885

RESUMO

BACKGROUND: Deferoxamine (DFX) has been reported to have neuroprotective effect. This study aimed to investigate the neuroprotective effect of DFX and its effect on hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in rats after traumatic brain injury (TBI). MATERIALS AND METHODS: Rats were randomly divided into sham operation, TBI + DFX, and TBI + vehicle groups. The rats in the TBI + DFX group were intraperitoneally injected with DFX 2 and 6 h after injury, thereafter once every 12 h. The rats in the TBI + vehicle group were intraperitoneally injected with saline at the same time points. At 6, 12, 24, and 48 h after TBI, 6 rats in each group were euthanized, and the brains were harvested. The expression of HIF-1α and VEGF in the pericontusional area was detected using real-time polymerase chain reaction and Western blot analysis. TBI-induced apoptosis was investigated using the TdT-mediated dUTP nick-end labeling (TUNEL) method. Three days after TBI, the density of microvessels was examined via immunohistochemical staining. RESULTS: DFX treatment upregulated the expression of HIF-1α and VEGF after TBI. DFX treatment reduced apoptosis and improved the neurobehavioral score after TBI. The density of microvessels was higher in the TBI + DFX group than that in the TBI + vehicle group 3 d after TBI. CONCLUSIONS: DFX can stimulate angiogenesis, inhibit apoptosis, and play a protective role after TBI. The protective effect of DFX may, at least in part, be through upregulating the expression of HIF-1α and its downstream target gene VEGF.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Desferroxamina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/patologia , Desferroxamina/uso terapêutico , Modelos Animais de Doenças , Humanos , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
9.
Nat Commun ; 10(1): 5134, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723130

RESUMO

Iron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO's own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.


Assuntos
Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Rim/patologia , Nanopartículas/química , Animais , Desferroxamina/farmacocinética , Desferroxamina/uso terapêutico , Desferroxamina/toxicidade , Quelantes de Ferro/química , Quelantes de Ferro/farmacologia , Masculino , Camundongos , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Distribuição Tecidual
10.
Artigo em Inglês | MEDLINE | ID: mdl-31658967

RESUMO

Siderophore-antibiotic conjugates have increased in vitro activity in low-iron environments where bacteria express siderophores and associated transporters. The host immune hypoferremic response reduces iron availability to bacteria; however, patients with iron overload or deficiency may have altered ability to restrict iron, which may affect the efficacy of siderophore-antibiotic conjugates. In vivo models of infection with iron overload and deficiency are needed to perform this assessment. The standard neutropenic murine thigh infection model was supplemented with iron-altering treatments: iron dextran at 100 mg/kg of body weight daily for 14 days to load iron or deferoxamine at 100 mg/kg daily plus a low-iron diet for up to 30 days to deplete iron. Human-simulated regimens of cefiderocol and meropenem were administered in both models to assess any impact of iron alteration on plasma pharmacokinetics. Median iron in overloaded mice was significantly higher than that of controls in plasma (1,657 versus 336 µg/dl; P < 0.001), liver (2,133 versus 11 µg/g; P < 0.001), and spleen (473 versus 144 µg/g; P < 0.001). At 30 days, depleted mice had significantly lower iron than controls in liver (2.4 versus 6.5 µg/g; P < 0.001) and spleen (72 versus 133 µg/g; P = 0.029) but not plasma (351 versus 324 µg/dl; P = 0.95). Cefiderocol and meropenem plasma concentrations were similar in iron overloaded and control mice but varied in iron-depleted mice. The iron-overloaded murine thigh infection model was established, and human-simulated regimens of cefiderocol and meropenem were validated therein. While deferoxamine successfully reduced liver and splenic iron, this depleting treatment altered the pharmacokinetics of both antimicrobials.


Assuntos
Antibacterianos/química , Antibacterianos/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/metabolismo , Sideróforos/química , Animais , Cefalosporinas/química , Cefalosporinas/uso terapêutico , Desferroxamina/química , Desferroxamina/uso terapêutico , Modelos Animais de Doenças , Feminino , Ferro , Meropeném/química , Meropeném/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana
11.
J. optom. (Internet) ; 12(3): 168-173, jul.-sept. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-185366

RESUMO

Purpose: To compare contrast sensitivity (CS) in multi-transfused β-thalassemia patients who received deferoxamine with those who received Osveral. Methods: In this cross sectional study a total of 60 Beta-thalassemia patients (30 used deferoxamine and 30 used deferasirox) were regarded as case group and 30 age and sex matched healthy subjects were selected as control group. All subjects had a set of examinations including refraction, visual acuity, Biomicroscopy, ophthalmoscopy and CS. Contrast threshold was assessed with the use of Freiberg visual acuity and contrast test under the mesopic light condition for three frequencies; 1, 5, 15cpd. All data analysis was performed using SPSS, version 17. Results: In visual acuity tests, thalassemic patients did not have any problem. Contrast threshold was higher in thalassemic patients who infuse deferoxamine (1.87 ± 0.63, 1.46 ± 0.81, and 2.96 ± 1.68 in 1, 5, and 15 cpd, respectively) than that of those who intake deferasirox (1.74 ± 0.80 (P = 0.743), 0.99 ± 0.74 (P = 0.047), and 2.42 ± 1.36 (P = 0.321) for 1, 5, and 15cpd, respectively), and also than healthy patients (1.33 ± 0.58 (P = 0.009), 0.95 ± 0.68 (P = 0.022), and 2.24 ± 1.23 (P = 0.135) for 1, 5, and 15cpd, respectively). Comparing those who used deferasirox with healthy subjects, contrast threshold was higher in deferasirox group at all special frequencies (P > 0.05). No significant relationship was observed between CS values and duration of transfusion, serum ferritin concentration and dose of chelation therapy (P > 0.05). Conclusions: CS tests can detect visual disturbance in thalassemic patients before the impairment of visual acuity. It is suggested that CS tests be included in their regular eye examination


Objetivo: Comparar la sensibilidad de contraste (SC) en pacientes multitrasfundidos con Beta-talasemia y tratados con deferoxamina u Osveral. Métodos: En este estudio transversal, un total de 60 pacientes con Beta-talasemia (30 tratados con deferoxamina y 30 con deferasirox) fueron considerados como grupo de estudio, y 30 sujetos sanos pareados por edad y sexo fueron seleccionados como grupo control. A todos los sujetos se les realizó una serie de exámenes que incluyeron refracción, agudeza visual, biomicroscopía, oftalmoscopía y SC. El umbral de contraste se valoró mediante la prueba de agudeza visual y contraste de Freiberg, en condiciones de visión mesópica para tres frecuencias: 1, 5 y 15 cpd. Todos los análisis de los datos se realizaron utilizando SPSS, versión 17. Resultados: En las pruebas de agudeza visual los pacientes con talasemia no tuvieron ningún problema. El umbral de contraste fue superior en los pacientes con talasemia a quienes se infundió deferoxamina (1,87 ± 0,63, 1,46 ± 0,81 y 2,96 ± 1,68 en 1, 5 y 15 cpd, respectivamente) que en los pacientes tratados con deferasirox (1,74 ± 0,8 (P = 0,743), 0,99 ± 0,74 (P = 0,047) y 2,42 ± 1,36 (P = 0,321) para 1, 5 y 15 cpd, respectivamente), y también en los pacientes sanos (1,33 ± 0,58 (P = 0,009), 0,95 ± 0,68 (P = 0,022) y 2,24 ± 1,23 (P = 0,135) para 1, 5 y 15 cpd, respectivamente). Al comparar los pacientes tratados con deferasirox y los sujetos sanos, el umbral de contraste fue superior en el grupo de deferasirox para todas las frecuencias especiales (P > 0,05). No se observó una relación significativa entre los valores de SC y la duración de la trasfusión, la concentración de ferritina sérica y la dosis de la terapia de quelación (P > 0,05). Conclusiones: Las pruebas de SC pueden detectar la alteración visual en los pacientes con talasemia con anterioridad al deterioro de la agudeza visual. Sugerimos la inclusión de las pruebas de SC en su examen ocular regular


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Sensibilidades de Contraste/fisiologia , Deferasirox/uso terapêutico , Desferroxamina/uso terapêutico , Sideróforos/uso terapêutico , Transtornos da Visão/fisiopatologia , Talassemia beta/tratamento farmacológico , Análise de Variância , Estudos de Casos e Controles , Estudos Transversais , Acuidade Visual/fisiologia , Talassemia beta/fisiopatologia
12.
Hemoglobin ; 43(3): 218-221, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31373517

RESUMO

Hypothyroidism is one of the common endocrine complications described in patients with ß-thalassemia major (ß-TM). Studies have reported its incidence and severity depending on the region, quality of management and treatment protocols. The reported thyroid dysfunction includes overt hypothyroidism, subclinical hypothyroidism and rarely, central hypothyroidism. The main aims of this study were to identify the incidence of hypothyroidism in 82 patients with ß-TM in Syria, and also to evaluate the effect of compliance with deferoxamine (DFO) therapy on the patients' thyroid function. Out of the 82 patients included in this study, 24 had subclinical hypothyroidism (29.27%) and one patient had overt hypothyroidism (1.22%). It was demonstrated by this study that noncompliance with DFO therapy increases the risk of thyroid dysfunction 6.38-times compared to compliance with DFO [risk ratio (RR) = 6.385; 95% confidence interval (95% CI) 2.40-16.95)]. These results emphasize the importance of compliance with chelation therapy to minimize the burden of thyropathy on patients' quality of life, and also augment the rationale for a routine follow-up and endocrine evaluation for early detection and management of these complications.


Assuntos
Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Adesão à Medicação , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/etiologia , Talassemia beta/complicações , Talassemia beta/epidemiologia , Adolescente , Adulto , Biomarcadores , Estudos de Casos e Controles , Criança , Estudos Transversais , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Feminino , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Masculino , Cooperação do Paciente , Síria/epidemiologia , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem , Talassemia beta/genética
13.
J Trace Elem Med Biol ; 56: 131-138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31466045

RESUMO

BACKGROUND: Cisplatin (CDDP) resistance remains a major obstacle for treatment of ovarian cancer. Iron contributes to the growth and reproduction of malignant cells, thus iron chalators can inhibit the growth of tumor cells by depleting the intracellular iron pool. The iron chelator, desferrioxamine (DFO), has performed anticancer in previous study. The aim of our study is to determine the correlation between iron-deprivation and tumor chemosensitivity in ovarian cancer. METHODS: To investigate the prognostic value of ferritin light (FTL), ferroportin (FPN), hepcidin (HAMP) and divalent metal-ion transporter-1 (DMT1) in ovarian cancer, the Kaplan-Meier analysis and the Gene Expression Profiling Interactive Analysis (GEPIA) were used. The ovarian cancer cell lines (SKOV-3 and OVCAR-3) were exposed to a gradient concentration of DFO (10, 20, 50, 100, 200 µM) and CDDP (1, 5, 10, 50,100 µM) for 24 h. The protein expression of FTL was tested. The expression of cancer stem cell (CSC) markers, including Sox2, Nanog and C-myc, were downregulated with treatment of DFO. Also, the mamosphere formation and the plation of CD44+/high/CD133+/high and Aldehyde dehydrogenase (ALDH)+/high SKOV-3 cells were reduced after treatment for 7d. Furthermore, we detected the expression of p53, BCL-2, BAX, and caspase-8. RESULTS: The survival analysis revealed that high expression of FTL, DMT1, HAMP, showed poor overall survival (OS) in ovarian cancer patients. Our combined data found that DFO could effectively inhibit CSCs, improve the resistance to chemotherapy, and significantly enhanced the efficacy of CDDP therapy in vitro in promoting apoptosis. Besides, targeting molecular targets, including BAX, BCL-2, p53 and caspase-8 could serve as the clinical biomarkers to evaluate the effects of ovarian cancer. It is reasonable to believe that DFO adjuvant therapy in combination with CDDP chemotherapy can promote the improvement of treatment response in ovarian cancer patients. CONCLUSION: Our research suggests the experimental evidence for DFO and CDDP as a new effective combination therapy to enhance the efficacy of chemical therapy in ovarian cancer.


Assuntos
Antineoplásicos/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Aldeído Desidrogenase/metabolismo , Antígenos CD/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Desferroxamina/farmacologia , Progressão da Doença , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Espaço Intracelular/metabolismo , Ferro/metabolismo , Quelantes de Ferro/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteína Supressora de Tumor p53/metabolismo
14.
Ear Nose Throat J ; 98(8): NP125-NP130, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31142160

RESUMO

Ocular and ophthalmological adverse effects may be seen in ß-thalassemia major (BTM) patients treated with regular blood transfusions and iron-chelating agents. We hypothesized that olfactory dysfunction may be present in this population. In this study, we aimed to investigate olfactory dysfunction in patients with BTM and determine the etiological factors. A total of 43 patients with BTM were included in the study. Forty-three patients without any nasal complaints, history of facial trauma, or nasal surgery were included as the controls. All participants had nasal endoscopy. The iron-chelating agents used, their duration of use, as well as hemoglobin and ferritin levels of the BTM patients were recorded. Sniffin' Sticks test (SST) was used to assess olfactory functions, and BTM and control groups were compared for the results. The correlations of SST scores with the other study parameters were analyzed. Eight (18.6%) of 43 patients in the BTM group had hyposmia while none of the patients in the control group had hyposmia (P < .001). Older age, low-hemoglobin level, and longer use of deferoxamine were found to be correlated with olfactory dysfunction. Olfactory dysfunction may be seen in BTM patients treated with iron-chelating agents. The results of this study suggest that screening for olfactory function may be needed in routine follow-up of BTM patients.


Assuntos
Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Transtornos do Olfato/etiologia , Talassemia beta/sangue , Talassemia beta/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Desferroxamina/efeitos adversos , Feminino , Ferritinas/sangue , Hemoglobinas/metabolismo , Humanos , Quelantes de Ferro/efeitos adversos , Masculino , Adulto Jovem , Talassemia beta/complicações
15.
Biomed Res Int ; 2019: 6573497, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119181

RESUMO

Background: Endocrinopathies are common in patients with ß-thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in ß-thalassemia major based on a meta-analysis. Methods: PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in ß-thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with ß-thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted. Results: A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in ß-thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in ß-thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias. Conclusion: High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in ß-thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.


Assuntos
Diabetes Mellitus/epidemiologia , Doenças do Sistema Endócrino/epidemiologia , Glucose/metabolismo , Talassemia beta/epidemiologia , Terapia por Quelação , Desferroxamina/uso terapêutico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/patologia , Intolerância à Glucose , Humanos , Quelantes de Ferro/uso terapêutico , Oriente Médio/epidemiologia , Talassemia beta/complicações , Talassemia beta/metabolismo , Talassemia beta/patologia
16.
World Neurosurg ; 128: e895-e904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082547

RESUMO

BACKGROUND: Brainstem hemorrhage (BSH) is the most dangerous and devastating subtype of intracerebral hemorrhage and is associated with high morbidity and mortality. However, to date, no effective prevention methods or specific therapies have been available to improve its clinical outcomes. We preliminarily explored the efficacy of deferoxamine (DFO), a clinical chelator known for its iron-scavenging activities, in a rat model of BSH induced with collagenase infusion. METHODS: DFO or saline was administrated 6 hours after BSH induction and then every 12 hours for ≤7 days. The survival curve of the rats was created, and the neurological scores were examined on days 1, 3, and 7 after BSH. The rats were sacrificed after 1, 3, and 7 days of DFO treatment for histological examination and immunohistochemistry. RESULTS: The results showed that administration of DFO delayed erythrocytes lysis, reduced iron deposition, reduced reactive oxygen species generation, reduced heme oxygenase-1 expression, and alleviated brain injury such as neuron degeneration and myelin sheath injury. However, DFO did not improve the survival rate and neurobehavioral outcomes in this model. CONCLUSIONS: Administration of DFO had limited therapeutic effects on collagenase-induced brainstem hemorrhage in rats. Some potential explanations were proposed, and more preclinical work is required to clarify the controversial curative effect of DFO in ICH.


Assuntos
Hemorragia do Tronco Encefálico Traumática/complicações , Quelantes/uso terapêutico , Desferroxamina/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Animais , Hemorragia do Tronco Encefálico Traumática/induzido quimicamente , Colagenases , Heme Oxigenase-1/metabolismo , Imuno-Histoquímica , Masculino , Bainha de Mielina/patologia , Degeneração Neural/prevenção & controle , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Análise de Sobrevida
17.
Lancet Neurol ; 18(5): 428-438, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30898550

RESUMO

BACKGROUND: Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial. METHODS: We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed. FINDINGS: We recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related. INTERPRETATION: Deferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile. FUNDING: US National Institutes of Health and US National Institute of Neurological Disorders and Stroke.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Idoso , Desferroxamina/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Quelantes de Ferro/efeitos adversos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Resultados Negativos , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento
18.
Pediatr Int ; 61(5): 444-448, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30882955

RESUMO

BACKGROUND: Iron intoxication can occur accidentally in children or intentionally by adolescents as a suicide attempt. They usually present with various symptoms including vomiting and diarrhea. Clinical studies in this field has been reported different doses of ingested elemental iron that caused serious toxicity, but none of these studies determined the minimum cut-off of ingested iron that triggered the risk of severe toxicity. The aim of this study was therefore to investigate the demographic features of iron intoxication in Turkish children and to determine the lowest cut-off of ingested elemental iron triggering serious intoxication and the need for prompt management. METHODS: This retrospective study investigated 83 Turkish patients with accidental and intentional iron poisoning. RESULTS: Of the 83 cases of acute iron intoxication, accidental iron consumption was more common than intentional use. Fifty-three patients ingested a median toxic dose of elemental iron of 40.0 mg/kg (IQR, 33.5 mg/kg). The median serum iron concentration in the first 6 h of ingestion was 150 µg/dL (IQR, 282 µg/dL). Twenty patients were given deferoxamine, whereas 63 patients were given supportive treatment. CONCLUSION: The cut-off of ingested elemental iron that triggered serious toxicity and the need for deferoxamine in children <18 years of age was 28 mg/kg.


Assuntos
Ingestão de Alimentos , Ferro/administração & dosagem , Ferro/envenenamento , Envenenamento/diagnóstico , Oligoelementos/administração & dosagem , Oligoelementos/envenenamento , Adolescente , Criança , Desferroxamina/uso terapêutico , Feminino , Humanos , Ferro/sangue , Masculino , Envenenamento/sangue , Envenenamento/tratamento farmacológico , Estudos Retrospectivos , Sensibilidade e Especificidade , Sideróforos/uso terapêutico , Oligoelementos/sangue , Turquia
19.
Expert Rev Hematol ; 12(4): 265-272, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30920854

RESUMO

OBJECTIVES: Three iron chelators are used to treat transfusion-dependent beta-thalassemia: desferrioxamine (DFO), deferasirox (DFX), and deferiprone (DFP). Compliance is low for DFO as it cannot be administered orally. Combined administration of DFP and DFX is orally available, however, the therapeutic mechanism is unknown. This pilot study investigated the iron removal mechanisms of DFX and DFP treatment in patients with transfusion-dependent thalassemia major. METHODS: Each patient received three treatments sequentially: (1) DFX monotherapy, (2) DFP monotherapy, and (3) DFX/DFP combination therapy with a four-day washout period between each treatment. Urine and stool specimens were collected to determine the primary outcome of iron excretion volumes. RESULTS: The mean iron excretion was seven times higher after combination therapy with DFX and DFP. Monotherapies also increased excretions volumes, though to a significantly lesser degree. Combined administration of DFX and DFP achieves maximum iron removal in transfusion-dependent thalassemia major compared to monotherapy with either drug. CONCLUSIONS: We suggest combination therapy in chronic severe iron overload cases, especially for patients in poor compliance with DFO/DFP combination therapy or those exhibiting poor iron removal from DFX or DFP monotherapy.


Assuntos
Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia beta/tratamento farmacológico , Administração Oral , Adulto , Transfusão de Sangue , Terapia por Quelação , Deferasirox/administração & dosagem , Deferiprona/administração & dosagem , Desferroxamina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Ferro/isolamento & purificação , Ferro/urina , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/urina , Masculino , Projetos Piloto , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/urina
20.
Int Immunopharmacol ; 69: 337-346, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30776642

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder accompanied with hyperalgesia, edema and pain. At least 30% of the patients failed to respond to the available treatments and medications, which yet have a lot of serious adverse effects on patients. So, using novel technologies to produce more efficient medications is needed. According to the role of iron manipulation in inflammatory process, we have synthetized RAc1 nano particle, which contains zinc and has iron chelating property. In the present study, we evaluated RAc1 nano particle effects on hyperalgesia and liver hepcidin and serum IL-1ß and TNF-α expression levels during acute and chronic phases of adjuvant-induced inflammation in male rats and compared its effects with Deferoxamine. METHODS AND MATERIALS: Complete Freund's adjuvant (CFA)-induced arthritis was caused by single subcutaneous injection of CFA into the rat's hind paw on day zero. RAc1 with 100, 200 and 400 ng/kg doses and deferoxamin with doses of 200 mg/kg after diluting in vehicles were administered daily (i.p.) during the 21 days of the study after CFA injection. Hyperalgesia, Edema, liver hepcidin and serum IL-1ß and TNF-α expression levels were assessed on days 0, 7, 14 and 21 of the study. RESULTS: The results of this study indicated the role of RAc1 nano particle administration in reducing paw edema, thermal hyperalgesia, and liver hepcidin and serum IL-1ß and TNF-α expression even in comparison with Deferoxamine during different phases of inflammation caused by CFA. CONCLUSION: It seems that RAc1 nano particle exerts its immune modulatory effects by decreasing liver hepcidin expression and serum IL-1ß and TNF-α levels.


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Nanopartículas/uso terapêutico , Animais , Desferroxamina/uso terapêutico , Hepcidinas/metabolismo , Humanos , Interleucina-1beta/sangue , Irã (Geográfico) , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Sideróforos/uso terapêutico , Fator de Necrose Tumoral alfa/sangue
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