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1.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
J Pediatr Hematol Oncol ; 41(3): 210-214, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30585946

RESUMO

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.


Assuntos
Terapia por Quelação/métodos , Adesão à Medicação/psicologia , Talassemia beta/terapia , Adolescente , Terapia por Quelação/psicologia , Criança , Estudos Transversais , Cultura , Deferasirox/administração & dosagem , Deferasirox/uso terapêutico , Desferroxamina/administração & dosagem , Desferroxamina/uso terapêutico , Feminino , Humanos , Jordânia , Masculino , Inquéritos e Questionários
13.
Biomaterials ; 188: 144-159, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30343257

RESUMO

The use of intracortical microelectrode arrays has gained significant attention in being able to help restore function in paralysis patients and study the brain in various neurological disorders. Electrode implantation in the cortex causes vasculature or blood-brain barrier (BBB) disruption and thus elicits a foreign body response (FBR) that results in chronic inflammation and may lead to poor electrode performance. In this study, a comprehensive insight into the acute molecular mechanisms occurring at the Utah electrode array-tissue interface is provided to understand the oxidative stress, neuroinflammation, and neurovascular unit (astrocytes, pericytes, and endothelial cells) disruption that occurs following microelectrode implantation. Quantitative real time polymerase chain reaction (qRT-PCR) was used to quantify the gene expression at acute time-points of 48-hr, 72-hr, and 7-days for factors mediating oxidative stress, inflammation, and BBB disruption in rats implanted with a non-functional 4 × 4 Utah array in the somatosensory cortex. During vascular disruption, free iron released into the brain parenchyma can exacerbate the FBR, leading to oxidative stress and thus further contributing to BBB degradation. To reduce the free iron released into the brain tissue, the effects of an iron chelator, deferoxamine mesylate (DFX), was also evaluated.


Assuntos
Barreira Hematoencefálica/patologia , Desferroxamina/uso terapêutico , Eletrodos Implantados/efeitos adversos , Corpos Estranhos/tratamento farmacológico , Corpos Estranhos/etiologia , Quelantes de Ferro/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Corpos Estranhos/metabolismo , Corpos Estranhos/patologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
14.
Bone ; 120: 156-165, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30385424

RESUMO

Deferoxamine (DFO) possesses a good chelating capability and is therefore used for the clinical treatment of ion deposition diseases. Increasing evidence shows that DFO can inhibit the activity of proline hydroxylase (PHD) by chelating iron, resulting in hypoxia-induced factor (HIF) signaling activation and angiogenesis promotion. However, clinical evidence indicates that a high concentration of DFO could be biotoxic due to its enrichment in related organs. Thus, we established a new compound by conjugating DFO with the bone-seeking agent iminodiacetic acid (IDA); the new agent is called SF-DFO, and we verified its promotion of HIF activation and tube formation in vivo. After confirming the bone-seeking property of SF-DFO in the femur and vertebra of both male and female mice and comparing it to that of DFO, we analyzed the protective effect of DFO and SF-DFO in an ovariectomized (OVX) mouse model. The serum CTX-I level revealed no influence of DFO and SF-DFO on osteoclast activity, but the blood vessels and osteoblasts in the metaphysis were more abundant after SF-DFO treatment, which resulted in a greater protective effect against trabecular bone loss compared to the DFO group. Additionally, the cortical parameters and bone strength performance were identical between the DFO and SF-DFO groups. However, the diffuse inflammatory response in the liver and spleen that occurred after DFO injection was not observed in the SF-DFO group. Thus, with reduced biotoxicity and an equivalent bone-seeking capability, SF-DFO may be a better choice for the prevention of vascular degradation-induced osteoporosis.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Osso e Ossos/irrigação sanguínea , Desferroxamina/uso terapêutico , Estrogênios/deficiência , Neovascularização Fisiológica , Animais , Animais Recém-Nascidos , Fenômenos Biomecânicos , Osso e Ossos/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Osso Cortical/anatomia & histologia , Osso Cortical/efeitos dos fármacos , Osso Cortical/fisiologia , Desferroxamina/química , Desferroxamina/farmacologia , Desferroxamina/toxicidade , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica/efeitos dos fármacos
15.
J Optom ; 12(3): 168-173, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29534970

RESUMO

PURPOSE: To compare contrast sensitivity (CS) in multi-transfused ß-thalassemia patients who received deferoxamine with those who received Osveral. METHODS: In this cross sectional study a total of 60 ß-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 15cpd, 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.


Assuntos
Sensibilidades de Contraste/fisiologia , Deferasirox/uso terapêutico , Desferroxamina/uso terapêutico , Sideróforos/uso terapêutico , Transtornos da Visão/fisiopatologia , Talassemia beta/tratamento farmacológico , Adulto , Análise de Variância , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Acuidade Visual/fisiologia , Adulto Jovem , Talassemia beta/fisiopatologia
16.
Acta Haematol ; 141(1): 32-42, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30504715

RESUMO

Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (> 30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.


Assuntos
Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/diagnóstico , Bases de Dados Factuais , Desferroxamina/uso terapêutico , Relação Dose-Resposta a Droga , Humanos , Ferro/análise , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/mortalidade , Miocárdio/química , Razão de Chances , Talassemia/complicações
17.
Turk J Pediatr ; 60(3): 335-339, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30511551

RESUMO

Khdair-Ahmad F, Aladily T, Khdair-Ahmad O, Badran EF. Chelation therapy for secondary neonatal iron overload: Lessons learned from rhesus hemolytic disease. Turk J Pediatr 2018; 60: 335-339. Secondary neonatal iron overload occurs with intrauterine and post-natal blood transfusions. Treatment with intravenous Deferoxamine was reported only in four cases in the literature. Herein we report a case of a patient born at 36 weeks of gestation, who had rhesus hemolytic disease. He developed secondary iron overload, causing liver injury, after a total of six blood transfusions: four intrauterine and 2 post-natal transfusion therapies. Intravenous Deferoxamine treatment was started at the age of 45 days due to a ferritin level of 40,000 mg/L, progressive rise of liver enzymes, and worsening cholestasis. Treatment resulted in marked reduction in ferritin level (down to 829 mg/L at the age of 6 months), significant improvement in the liver enzymes, and resolution of cholestasis.


Assuntos
Terapia por Quelação/métodos , Desferroxamina/uso terapêutico , Eritroblastose Fetal/terapia , Sobrecarga de Ferro/tratamento farmacológico , Isoimunização Rh/complicações , Transfusão de Sangue , Colestase/etiologia , Feminino , Ferritinas/sangue , Humanos , Lactente , Recém-Nascido , Sobrecarga de Ferro/etiologia , Fígado/patologia , Masculino , Gravidez , Isoimunização Rh/terapia
18.
Health Qual Life Outcomes ; 16(1): 216, 2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30453981

RESUMO

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.


Assuntos
Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Talassemia/tratamento farmacológico , Adulto , Transfusão de Sangue , Terapia por Quelação/métodos , Feminino , Humanos , Sobrecarga de Ferro/prevenção & controle , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/psicologia , Qualidade de Vida , Talassemia/psicologia
20.
Br J Haematol ; 183(5): 783-795, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30334574

RESUMO

We prospectively assessed the efficacy of deferasirox versus deferiprone or desferrioxamine as monotherapy in thalassaemia major (TM) patients by magnetic resonance imaging (MRI). We selected the patients enrolled in the Myocardial Iron Overload in Thalassaemia network who received only one chelator between two MRIs (deferasirox = 235, deferiprone = 142, desferrioxamine = 162). Iron overload was measured by T2* technique and biventricular function by cine images. Among the patients with baseline myocardial iron, in all three groups there was a significant improvement in global heart T2* values. The deferiprone and desferrioxamine groups showed a significant improvement in left ventricular ejection fraction (LVEF). Only the deferiprone group showed a significant improvement in right ventricular ejection fraction (RVEF). The improvement in global heart T2* was significantly lower in the deferasirox versus the deferiprone group. The improvement in the LVEF was significantly higher in the deferiprone and desferrioxamine groups than in the deferasirox group and the improvement in the RVEF was significantly higher in the deferiprone than in deferasirox group. Among the patients with baseline hepatic iron, the changes in hepatic iron were comparable in deferasirox versus the other groups. Deferasirox monotherapy was less effective than deferiprone in improving myocardial siderosis and biventricular function and less effective than desferrioxamine in improving the LVEF.


Assuntos
Deferasirox/uso terapêutico , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Talassemia beta/tratamento farmacológico , Adulto , Cardiomiopatias/complicações , Cardiomiopatias/tratamento farmacológico , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos , Resultado do Tratamento , Talassemia beta/complicações
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