RESUMEN
Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.
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Anemia Ferropénica , Compuestos Férricos , Maltosa , Complicaciones Hematológicas del Embarazo , Humanos , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/uso terapéutico , Embarazo , Maltosa/análogos & derivados , Maltosa/administración & dosificación , Maltosa/uso terapéutico , Anemia Ferropénica/tratamiento farmacológico , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Administración Intravenosa , Ferritinas/sangre , Hemoglobinas/análisisRESUMEN
OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS: We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].
Asunto(s)
Anemia Ferropénica , Anemia , Enfermedades Inflamatorias del Intestino , Humanos , Niño , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/etiología , Compuestos Férricos/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Maltosa/uso terapéutico , Hierro/uso terapéutico , Hemoglobinas , Administración Oral , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate trends in diagnosis and management of iron deficiency anemia using a large national children's hospital database in pediatric patients admitted with inflammatory bowel disease (IBD). STUDY DESIGN: In this retrospective multicenter cohort study, we used the Pediatric Health Information System de-identified administrative database. Patients age <21 years with ≥2 admissions with International Classification of Disease, Ninth Revision and Tenth Revision codes for Crohn's disease or ulcerative colitis from 2012 to 2018 were included. We extracted data regarding diagnoses of anemia and/or iron deficiency, and receipt of oral iron, intravenous (IV) iron, and/or blood transfusion. Data were analyzed descriptively. RESULTS: We identified 8007 unique patients meeting study criteria for a total of 28 260 admissions. The median age at admission was 15.4 years. A diagnosis of anemia was documented in 29.8% of admissions and iron studies were performed in 12.6%. IV iron was given in 6.3% of admissions and blood transfusions in 7.4%. The prevalence of the diagnosis of anemia among IBD admissions increased from 24.6% in 2012 to 32.4% in 2018 (P < .0001). There was a steady increase in the proportion of IBD admissions that used IV iron, from 3.5% in 2012 to 10.4% in 2018 (P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% (P < .0001). CONCLUSIONS: Iron deficiency anemia is prevalent among pediatric patients with IBD admitted to US children's hospitals. From 2012 to 2018, there was an increase in the use of inpatient IV iron for the treatment of iron deficiency anemia and a decrease in transfusions.
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Anemia Ferropénica/etiología , Anemia Ferropénica/terapia , Transfusión Sanguínea , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Compuestos Férricos/uso terapéutico , Sacarato de Óxido Férrico/uso terapéutico , Hematínicos/uso terapéutico , Complejo Hierro-Dextran/uso terapéutico , Adolescente , Anemia Ferropénica/epidemiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Lactante , Masculino , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.
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Compuestos Férricos/uso terapéutico , Tecnología Química Verde/métodos , Macrófagos/metabolismo , Nanopartículas de Magnetita/uso terapéutico , Animales , Sistemas de Liberación de Medicamentos , Compuestos Férricos/farmacocinética , Tecnología Química Verde/economía , Hipertermia Inducida/métodos , Nanopartículas de Magnetita/análisis , Nanopartículas de Magnetita/ultraestructura , Ratones , Células RAW 264.7RESUMEN
OBJECTIVE: To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model. METHODS: The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia. RESULTS: The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence. CONCLUSION: The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.
Asunto(s)
Neoplasias Encefálicas/terapia , Compuestos Férricos/uso terapéutico , Glioblastoma/terapia , Hipertermia Inducida/métodos , Magnetoterapia/métodos , Nanopartículas de Magnetita/uso terapéutico , Análisis de Varianza , Animales , Temperatura Corporal , Línea Celular Tumoral , Modelos Animales de Enfermedad , Compuestos Férricos/química , Mediciones Luminiscentes , Nanopartículas de Magnetita/química , Masculino , Ratas Wistar , Valores de Referencia , Reproducibilidad de los Resultados , Factores de Tiempo , Resultado del TratamientoRESUMEN
Abstract Introduction: Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group. Objective: To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden. Methods: A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO. Results: A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment. Conclusion: During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.
Resumo Introdução: A hiperfosfatemia é uma grave consequência da doença renal crônica associada a risco aumentado de doença cardiovascular. O controle dos níveis séricos de fósforo dos pacientes em diálise é um desafio que requer, na maioria dos casos, o uso de quelantes de fosfato (QF). Parte da dificuldade se deve à baixa adesão ao tratamento oriunda do grande número de medicamentos receitados para esse grupo de pacientes. Objetivo: Avaliar a real eficácia do oxihidróxido sucroférrico (OHS) no controle dos níveis séricos de fósforo e determinar a carga de comprimidos associada. Métodos: Estudo multicêntrico, quantitativo, retrospectivo, antes e depois conduzido com pacientes em hemodiafiltração on-line. Pacientes remanejados para OHS como parte dos cuidados de rotina foram incluídos no estudo. Tratamento com QF, número de comprimidos, níveis séricos de fósforo, reposição férrica endovenosa e dosagens foram registrados mensalmente durante seis meses de tratamento com QF ou OHS. Resultados: Foram incluídos 42 pacientes no estudo. Após a mudança de QF para OHS, o número de comprimidos prescritos por dia caiu em 67%, de seis para duas unidades diárias (p < 0,001). A frequência de ingestão de comprimidos caiu de três para duas vezes ao dia (p < 0,001). Durante o tratamento com OHS, o percentual de pacientes com fósforo sérico ≤ 5,5 mg/dL aumentou de 33,3% no início para 45% após seis meses de tratamento. Conclusão: Durante os seis meses de seguimento com OHS, os níveis séricos de fósforo foram controlados com um terço dos comprimidos por dia em relação aos tratamentos com outros QF.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Sacarosa/uso terapéutico , Compuestos Férricos/uso terapéutico , Hemodiafiltración , Hiperfosfatemia/tratamiento farmacológico , Fósforo/sangre , Estudios Retrospectivos , Estudios de Seguimiento , Resultado del Tratamiento , Combinación de Medicamentos , Insuficiencia Renal Crónica/complicaciones , Hiperfosfatemia/etiología , Cumplimiento de la Medicación , Sevelamer/efectos adversos , Sevelamer/uso terapéuticoRESUMEN
INTRODUCTION: Hyperphosphatemia is a serious consequence of chronic kidney disease and has been associated with an increased risk for cardiovascular disease. Controlling serum phosphorus levels in patients on dialysis is a challenge for the clinicians and implies, in most cases, the use of phosphate binders (PB). Part of the reason for this challenge is poor adherence to treatment because of the high pill burden in this patient group. OBJECTIVE: To assess the real-world effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus levels and determine the associated pill burden. METHODS: A multicenter, quantitative, retrospective, before-after study was conducted with patients receiving online hemodiafiltration. Patients who switched to SO as a part of routine care were included in the study. PB treatment, number of pills, serum phosphorus levels, and intravenous iron medication and dosage were collected monthly during the six months of treatment with either PB or SO. RESULTS: A total of 42 patients were included in the study. After switching from a PB to SO, the prescribed pills/day was reduced 67% from 6 pills/day to 2 pills/day (p < 0.001) and the frequency of pill intake was lowered from 3 times/day to 2 times/day (p < 0.001). During the treatment with SO, the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 33.3% at baseline to 45% after six months of treatment. CONCLUSION: During the six-month follow-up with SO, serum phosphorus levels were controlled with one third of the pills/day compared to other PB.
Asunto(s)
Compuestos Férricos/uso terapéutico , Hemodiafiltración , Hiperfosfatemia/tratamiento farmacológico , Sacarosa/uso terapéutico , Adulto , Anciano , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Hiperfosfatemia/etiología , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Fósforo/sangre , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Sevelamer/efectos adversos , Sevelamer/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the therapeutic response and adverse effects of Noripurum EV® in children and adolescents with inflammatory bowel disease (IBD) and iron deficiency anemia. MATERIALS AND METHODS: Cohort study involving patients with Crohn's disease (CD) and ulcerative colitis (UC) who received treatment for iron deficiency anemia with Noripurum EV®. Anemia was defined according to WHO 2011 criteria. Iron deficiency anemia was established when ferritin <30µg/l and transferrin saturation <16%. Iron deficiency anemia and anemia of chronic disease were established when ferritin was between 30 and 100µg/l and transferrin saturation <16%. The total dose of Noripurum EV® was estimated by the Ganzoni formula and divided into weekly administrations. When there was an increase in hemoglobin (Hb) by a minimum of 2g/dl and or when Hb reached the target determined by WHO, treatment was considered a therapeutic success. RESULTS: Noripurum EV® was administered to 16 patients (9.3% of total patients with IBD). Ten (65.5%) were male, the mean (SD) age was 11.3(4.6) years old, 75%(12/16) had CD and 25%(4/16) had UC. All patients presented an increase in Hb (p < .001) at a mean (SD) of 2.8(1.3)g/dl, after median and interquartile range(IQR) of 4.5(3.0-6.0) weeks that iron infusions were completed. It was found that the proportion of patients that achieved therapeutic success (68.8%) was statistically higher (p = .031) than those who did not (31.2%). No adverse events were reported. CONCLUSION: Noripurum EV® in pediatric patients with IBD and iron deficiency anemia was effective and safe, making it an appropriate option for the clinical management of these patients.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Colitis Ulcerosa/complicaciones , Enfermedad de Crohn/complicaciones , Compuestos Férricos/uso terapéutico , Hematínicos/uso terapéutico , Administración Intravenosa , Adolescente , Brasil , Niño , Estudios de Cohortes , Femenino , Compuestos Férricos/administración & dosificación , Compuestos Férricos/efectos adversos , Ferritinas/sangre , Hematínicos/administración & dosificación , Hematínicos/efectos adversos , Hemoglobinas/metabolismo , Humanos , Masculino , Calidad de Vida , Índice de Severidad de la Enfermedad , Transferrina/metabolismoRESUMEN
ABSTRACT Objective: To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model. Methods: The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia. Results: The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence. Conclusion: The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.
RESUMO Objetivo: Avaliar o potencial da técnica de magneto-hipertermia utilizando nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana em modelo de tumores de glioblastoma. Métodos: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram avaliadas quanto à sua estabilidade em meio aquoso e a seu potencial de aquecimento pela taxa de absorção específica, quando submetidas à magneto-hipertermia, com diferentes frequências e intensidades de campo magnético alternado. Nos ensaios de magneto-hipertermia in vitro, as células C6 cultivadas e transduzidas com luciferase foram avaliadas por bioluminescência na presença/ausência do campo magnético alternado, como também com e sem nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana. No estudo in vivo, a medida de bioluminescência foi adquirida no 21º dia após indução do glioblastoma com células C6 nos ratos. Após 24 horas, as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram implantadas no animal, tendo sido realizada a magneto-hipertermia por 40 minutos, nas melhores condições de frequência e intensidade de campo magnético alternado testado no estudo in vitro (maior valor da taxa de absorção específica); foi verificada a diferença do bioluminescência antes e após a magneto-hipertermia. Resultados: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana se mostraram estáveis, e sua capacidade de aquecimento aumentou com o incremento da frequência e da intensidade de campo magnético alternado. A aplicação da magneto-hipertermia, com 874kHz e 200 Gauss do campo magnético alternado, determinou o melhor valor da taxa de absorção específica (194,917W/g). Quando utilizados, estes parâmetros de magneto-hipertermia in vitro resultaram em morte celular de 52,0% e in vivo de 32,8% por bioluminescência. Conclusão: A técnica de magneto-hipertermia foi promissora para o processo terapêutico de tumores de glioblastoma no modelo animal utilizando as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana recobertas com aminosilana, que apresentaram alta taxa de absorção específica.
Asunto(s)
Animales , Masculino , Neoplasias Encefálicas/terapia , Compuestos Férricos/uso terapéutico , Glioblastoma/terapia , Magnetoterapia/métodos , Nanopartículas de Magnetita/uso terapéutico , Hipertermia Inducida/métodos , Valores de Referencia , Factores de Tiempo , Temperatura Corporal , Compuestos Férricos/química , Reproducibilidad de los Resultados , Análisis de Varianza , Resultado del Tratamiento , Ratas Wistar , Línea Celular Tumoral , Modelos Animales de Enfermedad , Nanopartículas de Magnetita/química , Mediciones LuminiscentesRESUMEN
BACKGROUND: Iron Deficiency Anemia (IDA) is a major public health problem worldwide. Iron Bisglycinate Chelate (FeBC) and polymaltose iron (FeP) are used for the treatment of IDA and exhibit good tolerability with a low incidence of adverse effects. However, these compounds have important differences in their structures and bioavailability. OBJECTIVE: To compare the efficacy of oral supplementation with FeBC and FeP in anemic children. METHODS: In this double-blind study, children aged 1 to 13 years who were diagnosed with IDA were randomly divided into two groups: i) FeBC, supplemented with iron bisglycinate chelate, and ii) FeP, supplemented with polymaltose iron (3.0 mg iron/kg body weight/day for 45 days for both groups). RESULTS: Both treatments resulted in significant increases in hemoglobin levels, Mean Corpuscular Volume (MCV) and Cell Distribution Width (RDW) and in a reduction of transferrin levels, relative to initial values. However, only FeBC treatment significantly increased ferritin and Mean Corpuscular Hemoglobin (MCH) levels. A significant negative correlation was observed between the increase in ferritin and initial hemoglobin levels in the FeBC group, indicating that the absorption of FeBC is regulated by the body iron demand. CONCLUSION: These results provide preliminary evidence to suggest a greater efficacy of FeBC than FeP in increasing iron stores.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos Férricos/uso terapéutico , Hematínicos/uso terapéutico , Hierro/uso terapéutico , Adolescente , Niño , Preescolar , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Índices de Eritrocitos/efectos de los fármacos , Ferritinas/sangre , Hemoglobinas/análisis , Humanos , Lactante , Proyectos Piloto , Transferrina/análisis , Resultado del TratamientoRESUMEN
Phosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH-FeCl and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 ± 18.56 versus 144.98 ± 22.1 µmol/L; p = 0.0001) and week 7 (41.55 ± 22.1 versus 83.98 ± 18.56 µmol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH-FeCl had a 54.5% reduction in serum phosphate (6.10 ± 2.23 versus 2.78 ± 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 ± 1.45 versus 3.52 ± 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 ± 18.56 versus 83.10 ± 23.87 µmol/L, p = 0.888); however, the CH-FeCl-treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 ± 0.2 versus 0.4 ± 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH-FeCl had an efficient chelating action on phosphate.
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Quelantes/uso terapéutico , Quitosano/uso terapéutico , Compuestos Férricos/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Uremia/tratamiento farmacológico , Adenina/toxicidad , Animales , Quelantes/química , Quitosano/química , Creatinina/sangre , Modelos Animales de Enfermedad , Compuestos Férricos/química , Humanos , Hiperfosfatemia/sangre , Hiperfosfatemia/tratamiento farmacológico , Fosfatos/sangre , Fosfatos/química , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/inducido químicamente , Uremia/sangreRESUMEN
Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.
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Compuestos Férricos/farmacocinética , Compuestos Ferrosos/farmacocinética , Alimentos Fortificados , Infecciones por Helicobacter/complicaciones , Absorción Intestinal , Hierro/farmacocinética , Triticum/química , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/prevención & control , Disponibilidad Biológica , Pan , Preescolar , Dieta , Ácido Edético/sangre , Ácido Edético/farmacocinética , Ácido Edético/uso terapéutico , Eritrocitos/metabolismo , Femenino , Compuestos Férricos/sangre , Compuestos Férricos/uso terapéutico , Compuestos Ferrosos/sangre , Compuestos Ferrosos/uso terapéutico , Harina , Haití , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Humanos , Hierro/sangre , Hierro/uso terapéutico , Deficiencias de Hierro , Masculino , Comidas , Adulto JovenRESUMEN
The cytotoxic response, cellular uptake, and metabolomic profile of HeLa and HaCaT cell lines treated with cobalt ferrite nanoparticles (CoFe2O4 NPs) were investigated in this study. Cell viability assays showed low cytotoxicity caused by the uptake of the nanoparticles at 2 mg/mL. However, metabolomics revealed that these nanoparticles impacted cell metabolism even when tested at a concentration that presented low cytotoxicity according to the cell viability assay. The two cell lines shared stress-related metabolic changes such as increase in alanine and creatine levels. A reduced level of fumarate was also observed in HeLa cells after treatment with the nanoparticles, and this alteration can inhibit tumorigenesis. Fumarate is considered to be an oncometabolite that can inhibit prolyl hydroxylase, and this inhibition stabilizes HIF1α, one of the master regulators of tumorigenesis that promotes tumor growth and development. In summary, this study showed that nanoparticle-treated HeLa cells demonstrated decreased concentrations of metabolites associated with cell proliferation and tumor growth. The results clearly indicated that treatment with these nanoparticles might cause a perturbation in cellular metabolism.
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Cobalto/farmacología , Compuestos Férricos/farmacología , Nanopartículas/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cobalto/uso terapéutico , Femenino , Compuestos Férricos/uso terapéutico , Fumaratos/farmacología , Células HeLa , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Metabolómica/métodos , Nanopartículas/uso terapéutico , Neoplasias/patología , Neoplasias del Cuello Uterino/metabolismoRESUMEN
Iron is an important micronutrient, but it can also act as a dangerous element by interfering with glucose homeostasis and inflammation, two features that are already disturbed in obese subjects. In this work, we study the effects of systemic iron supplementation on metabolic and inflammatory responses in mice with hypoferremia induced by obesity to better characterize whether iron worsens the parameters that are already altered after 24 weeks of a high-fat diet (HFD). Mice were maintained on a control diet or a HFD for 24 weeks and received iron-III polymaltose (50 mg/kg/every 2 days) during the last two weeks. Glucose homeostasis (basal glucose and insulin test tolerance) and systemic and visceral adipose tissue (VAT) inflammation were assessed. Iron levels were measured in serum. The Prussian blue reaction was used in isolated macrophages to detect iron deposition. Iron supplementation resulted in an increased number of VAT macrophages that were positive for Prussian blue staining as well as increased serum iron levels. Systemic hepcidin, leptin, resistin, and monocyte chemoattractant protein-1 (MCP-1) levels were not altered by iron supplementation. Local adipose tissue inflammation was also not made worse by iron supplementation because the levels of hepcidin, MCP-1, leptin, and interleukin (IL)-6 were not altered. In contrast, iron supplementation resulted in an increased production of IL-10 by adipose tissue and VAT macrophages. Leukocytosis and VAT plasminogen activator inhibitor-1 (PAI-1) level were reduced, but insulin resistance was not altered after iron supplementation. In conclusion, systemic iron supplementation in mice with hypoferremia induced by obesity did not worsen inflammatory marker or adipose tissue inflammation or the metabolic status established by obesity. Iron deposition was observed in adipose tissue, mainly in macrophages, suggesting that these cells have mechanisms that promote iron incorporation without increasing the production of inflammatory mediators.
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Anemia Ferropénica/etiología , Compuestos Férricos/uso terapéutico , Obesidad/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Animales , Glucemia/análisis , Citocinas/sangre , Suplementos Dietéticos , Hepcidinas/sangre , Inflamación/tratamiento farmacológico , Inflamación/etiología , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Hierro/sangre , Masculino , RatonesRESUMEN
BACKGROUND: Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD. METHODS: This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11-12 g/dL and iron deficiency (ferritin <100 µg/L or transferrin saturation <20%), who were regularly treated with oral iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study. RESULTS: Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 µg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study. CONCLUSION: Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02232906.
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Eritropoyesis/efectos de los fármacos , Compuestos Férricos/uso terapéutico , Hemoglobinas/metabolismo , Hierro/administración & dosificación , Hierro/uso terapéutico , Maltosa/análogos & derivados , Insuficiencia Renal Crónica/tratamiento farmacológico , Administración Intravenosa , Administración Oral , Anciano , Anciano de 80 o más Años , Femenino , Compuestos Férricos/administración & dosificación , Humanos , Masculino , Maltosa/administración & dosificación , Maltosa/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/sangreRESUMEN
AIM: The aim of this study was to evaluate the scientific evidence of pulpotomy in primary teeth comparing mineral troxide aggregate (MTA), calcium hydroxide, ferric sulphate, and electrosurgery with formocresol. METHODS: A systematic search using key words was conducted using seven databases up to December 10, 2013. Clinical articles in English, Portuguese and Spanish were selected, which were in accordance with the inclusion and exclusion criteria and the research objective of comparing whether pulpotomy performed with formocresol in primary teeth is more effective than other medicaments or techniques. RESULTS: Out of the 12,515 publication initially identified, 30 clinical articles were included in the systematic review and analysed by four meta-analyses. The success rate of MTA (94.6 %) was higher than that of formocresol (87.4 %), with a statistically significant difference (OR = 0.39; 95 % CI = 0.25-0.62). Formocresol pulpotomy success was not statistically different from ferric sulphate or electrosurgery. CONCLUSION: MTA was clinically and radiographically superior to formocresol for pulpotomy of primary teeth. The other alternatives to formocresol such as electrosurgery and ferric sulphate can be used instead of formocresol since they showed success similar to formocresol. In addition, there is no evidence to support calcium hydroxide for pulpotomies in primary teeth.
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Electrocirugia/métodos , Pulpotomía/métodos , Irrigantes del Conducto Radicular/uso terapéutico , Diente Primario/patología , Compuestos de Aluminio/uso terapéutico , Compuestos de Calcio/uso terapéutico , Hidróxido de Calcio/uso terapéutico , Combinación de Medicamentos , Compuestos Férricos/uso terapéutico , Formocresoles/uso terapéutico , Humanos , Óxidos/uso terapéutico , Silicatos/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Although there is an increase in clinical trials assessing the efficacy of cell therapy in structural and functional regeneration after stroke, there are not enough data in the literature describing the best cell type to be used, the best route, and also the best nanoparticle to analyze these stem cells in vivo. This review analyzed published data on superparamagnetic iron oxide nanoparticle (SPION)-labeled stem cells used for ischemic stroke therapy. METHOD: We performed a systematic review and meta-analysis of data from experiments testing the efficacy of cellular treatment with SPION versus no treatment to improve behavioral or modified neural scale outcomes in animal models of stroke by the Cochrane Collaboration and indexed in EMBASE, PubMed, and Web of Science since 2000. To test the impact of study quality and design characteristics, we used random-effects meta-regression. In addition, trim and fill were used to assess publication bias. RESULTS: The search retrieved 258 articles. After application of the inclusion criteria, 24 reports published between January 2000 and October 2014 were selected. These 24 articles were analyzed for nanoparticle characteristics, stem cell types, and efficacy in animal models. CONCLUSION: This study highlights the therapeutic role of stem cells in stroke and emphasizes nanotechnology as an important tool for monitoring stem cell migration to the affected neurological locus.
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Isquemia Encefálica/terapia , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Compuestos Férricos/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Accidente Cerebrovascular/terapia , Animales , Modelos Animales de Enfermedad , Humanos , Nanopartículas de Magnetita/uso terapéutico , Coloración y Etiquetado , Trasplante de Células Madre , Células Madre/fisiologíaRESUMEN
With the challenge of optimizing iron delivery, new intravenous (iv) iron-carbohydrate complexes have been developed in the last few years. A good example of these new compounds is ferric carboxymaltose (FCM), which has recently been approved by the US Food and Drug Administration for the treatment of iron deficiency anemia in adult patients who are intolerant to oral iron or present an unsatisfactory response to oral iron, and in adult patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). FCM is a robust and stable complex similar to ferritin, which minimizes the release of labile iron during administration, allowing higher doses to be administered in a single application and with a favorable cost-effective rate. Cumulative information from randomized, controlled, multicenter trials on a diverse range of indications, including patients with chronic heart failure, postpartum anemia/abnormal uterine bleeding, inflammatory bowel disease, NDD-CKD, and those undergoing hemodialysis, supports the efficacy of FCM for iron replacement in patients with iron deficiency and iron-deficiency anemia. Furthermore, as FCM is a dextran-free iron-carbohydrate complex (which has a very low risk for hypersensitivity reactions) with a small proportion of the reported adverse effects in a large number of subjects who received FCM, it may be considered a safe drug. Therefore, FCM appears as an interesting option to apply high doses of iron as a single infusion in a few minutes in order to obtain the quick replacement of iron stores. The present review on FCM summarizes diverse aspects such as pharmacology characteristics and analyzes trials on the efficacy/safety of FCM versus oral iron and different iv iron compounds in multiple clinical scenarios. Additionally, the information on cost effectiveness and data on change in quality of life are also discussed.