RESUMEN
Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.
Asunto(s)
Anemia Ferropénica/dietoterapia , Proteínas de Transporte de Catión/genética , Compuestos Férricos/farmacología , Hierro/metabolismo , Adsorción/efectos de los fármacos , Adulto , Anemia Ferropénica/genética , Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Animales , Disponibilidad Biológica , Suplementos Dietéticos/efectos adversos , Femenino , Compuestos Férricos/química , Compuestos Ferrosos/farmacología , Alimentos Fortificados/efectos adversos , Humanos , Hierro/farmacología , Radioisótopos de Hierro/farmacología , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Nanoestructuras/uso terapéutico , Adulto JovenRESUMEN
Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.
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Anemia Ferropénica/tratamiento farmacológico , Hematínicos/uso terapéutico , Fallo Renal Crónico/tratamiento farmacológico , Inhibidores de Prolil-Hidroxilasa/uso terapéutico , Anemia Ferropénica/dietoterapia , Anemia Ferropénica/patología , Diálisis , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hierro/uso terapéutico , Fallo Renal Crónico/enzimología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patologíaRESUMEN
We aimed to assess risk factors for anemia at delivery by conducting a secondary analysis of a prospective cohort study database including 1527 women who delivered vaginally ≥ 36 gestational weeks. Anemia (Hemoglobin (Hb) < 10.5 g/dL) was assessed at delivery. A complete blood count results during pregnancy as well as maternal and obstetrical characteristics were collected. The primary endpoint was to determine the Hb cutoff between 24 and 30 gestational weeks that is predictive of anemia at delivery by using the area under the curve (AUC) of the receiver operating characteristic curve. Independent risk factors for anemia at delivery were assessed using stepwise multivariable logistic regression. Hb and infrequent iron supplement treatment were independent risk factors for anemia at delivery (OR 0.3 95%CI [0.2-0.4] and OR 2.4 95%CI [1.2-4.8], respectively; C statistics 83%). Hb 10.6 g/dL was an accurate cutoff to predict anemia at delivery (AUC 80% 95%CI 75-84%; sensitivity 75% and specificity 74%). Iron supplement was beneficial to prevent anemia regardless of Hb value. Altogether, Hb should be routinely tested between 24 and 30 gestational weeks to screen for anemia. A flow chart for anemia screening and treatment during pregnancy is proposed in the manuscript.Trial registration: ClinicalTrials.gov Identifier: NCT02434653.
Asunto(s)
Anemia Ferropénica/sangre , Anemia/sangre , Hemoglobinas/genética , Hierro/metabolismo , Adulto , Anemia/genética , Anemia/metabolismo , Anemia/patología , Anemia Ferropénica/genética , Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Área Bajo la Curva , Recuento de Células Sanguíneas , Parto Obstétrico , Femenino , Hemoglobinas/aislamiento & purificación , Hemoglobinas/metabolismo , Humanos , Embarazo , Factores de RiesgoRESUMEN
Anaemia is common, particularly in women and the commonest underlying cause, iron deficiency, is often overlooked. Anaemia is associated with increased morbidity and mortality in patients undergoing anaesthesia; however, women are defined as being anaemic at a lower haemoglobin level than men. In this narrative review, we present the history of iron deficiency anaemia and how women's health has often been overlooked. Iron deficiency was first described as 'chlorosis' and a cause of 'hysteria' in women and initial treatment was by iron filings in cold wine. We present data of population screening demonstrating how common iron deficiency is, affecting 12-18% of apparently 'fit and healthy' women, with the most common cause being heavy menstrual bleeding; both conditions being often unrecognised. We describe a range of symptoms reported by women, that vary from fatigue to brain fog, hair loss and eating ice. We also describe experiments exploring the physical impact of iron deficiency, showing that reduced exercise performance is related to iron deficiency independent of haemoglobin concentration, as well as the impact of iron supplementation in women improving oxygen consumption and fitness. Overall, we demonstrate the need to single out women and investigate iron deficiency rather than accept the dogma of normality and differential treatment; this is to say, the need to change the current standard of care for women undergoing anaesthesia.
Asunto(s)
Anemia Ferropénica/patología , Anemia Ferropénica/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Metabolismo Energético , Fatiga/etiología , Femenino , Hemoglobinas/análisis , Humanos , Hierro/administración & dosificación , Hierro/metabolismo , Consumo de Oxígeno , Rendimiento Físico FuncionalRESUMEN
Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21 days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0 g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p < 0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p < 0.001) and of stroke (3.7% vs. 1.2%, p = 0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p = 0.230). In patients where the presenting haemoglobin was less than 130 g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.
Asunto(s)
Anemia/patología , Hierro/administración & dosificación , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Anemia/mortalidad , Anemia/cirugía , Anemia Ferropénica/mortalidad , Anemia Ferropénica/patología , Anemia Ferropénica/cirugía , Procedimientos Quirúrgicos Cardíacos , Transfusión de Eritrocitos , Femenino , Hemoglobinas/análisis , Mortalidad Hospitalaria , Humanos , Hierro/efectos adversos , Hierro/sangre , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Terapia de Reemplazo Renal , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Adulto JovenRESUMEN
Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products.
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Anemia Ferropénica/tratamiento farmacológico , Compuestos de Hierro/uso terapéutico , Hierro/uso terapéutico , Nanopartículas/uso terapéutico , Administración Intravenosa , Anemia Ferropénica/patología , Carbohidratos/química , Carbohidratos/uso terapéutico , Humanos , Hierro/metabolismo , Compuestos de Hierro/química , Nanomedicina/tendencias , Nanopartículas/química , Tamaño de la PartículaRESUMEN
Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.
Asunto(s)
Anemia Ferropénica/inducido químicamente , Anestésicos por Inhalación/toxicidad , Disfunción Cognitiva/inducido químicamente , Fibras Nerviosas Mielínicas/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Sevoflurano/toxicidad , Administración por Inhalación , Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Anestésicos por Inhalación/administración & dosificación , Animales , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Femenino , Ratones , Ratones Endogámicos C57BL , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Sevoflurano/administración & dosificaciónRESUMEN
Anaemia in pregnancy is a major health problem and an important cause of adverse foetomaternal outcomes in developing countries. Iron deficiency is the cause of the overwhelming majority of the cases of anaemia in pregnancy. Iron deficiency anaemia (IDA) has been linked with adverse foetal and maternal outcomes. This study investigated the prevalence of IDA and evaluated its effects on foetomaternal outcomes among parturients in Lagos, Nigeria. This was a cross-sectional study that enrolled 220 women aged 15-49 years with singleton gestation at term, between May 1, 2016, and March 31, 2017. Participants were selected by systematic sampling and baseline data were collected through interviews. Venous blood samples were obtained to measure haemoglobin and serum ferritin concentrations, and the associations between IDA (defined as anaemia and iron deficiency) and pregnancy outcomes were examined. A P-value <0.05 was considered as statistically significant. The prevalence of IDA was 12.3%. Routine antenatal iron supplementation (adjusted odds ratio 0.18, 95% confidence interval 0.07-0.46; P = 0.001) and interpregnancy interval of at least 2 years (adjusted odds ratio 0.20, 95% confidence interval 0.05-0.97; P = 0.021) have significant association with IDA. Iron deficiency anaemia was not significantly associated with adverse perinatal outcomes but there were significant associations with increased risk of blood transfusion (P = 0.001) and maternal infectious morbidities such as puerperal pyrexia (P = 0.041) and wound infection (P = 0.020). IDA is still a fairly common condition among parturients in Lagos and it's mostly associated with maternal peripartum morbidities. Adequate pregnancy spacing through the use of effective contraception and routine antenatal iron supplementations in pregnancy is a recommended preventive measure against IDA and its adverse sequelae. Future studies should adopt the use of transferrin saturation (TSAT) in compliment with serum ferritin assay as a more sensitive marker of iron deficiency.
Asunto(s)
Anemia Ferropénica/epidemiología , Hierro/sangre , Complicaciones Hematológicas del Embarazo/epidemiología , Resultado del Embarazo/epidemiología , Adolescente , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Anemia Ferropénica/patología , Femenino , Hemoglobinas/metabolismo , Humanos , Persona de Mediana Edad , Nigeria/epidemiología , Embarazo , Complicaciones Hematológicas del Embarazo/patología , Prevalencia , Adulto JovenRESUMEN
Chronic renal failure involving hemodialysis results in blood loss during filtration. Iron deficiency and iron deficiency anemia can result. A compensatory increase in iron dosage has many side effects including discomfort. Elemental iron is a highly-pure iron source, which reduces the frequency of dosages; the solubility decreases with increased particle size or pore size. In this study, synthesized mesoporous iron particles (MIPs) were used to relieve iron deficiency anemia. Their bioavailability was measured in vitro by a Caco-2 cell model and in vivo in iron-deficient rats. In vitro bioavailability of MIPs was examined by measuring ferritin content in the Caco-2 cell model. Iron uptake of MIPs was significantly higher than commercial iron particles, which were less porous. In vivo bioavailability of MIPs was examined by measuring body weight gain and red blood cell-related parameters, compared with the bioavailability of standard drug ferrous sulfate in iron-deficient anemic rats. Finally, average hemoglobin content and hemoglobin regeneration efficiency were significantly higher in anemic rats supplemented with commercial iron particles, compared to anemic controls. In the 28-day oral toxicity test, MIPs were not significantly toxic to rat physiology or tissue histopathology. Thus, MIPs may allow effective recovery of hemoglobin in iron deficiency anemia.
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Anemia Ferropénica/tratamiento farmacológico , Hierro/química , Nanopartículas/uso terapéutico , Administración Oral , Anemia Ferropénica/patología , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacocinética , Materiales Biocompatibles/uso terapéutico , Peso Corporal/efectos de los fármacos , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Ferritinas/análisis , Ferritinas/metabolismo , Compuestos Ferrosos/farmacología , Compuestos Ferrosos/uso terapéutico , Hemoglobinas/metabolismo , Humanos , Masculino , Nanopartículas/química , Nanopartículas/metabolismo , Tamaño de la Partícula , Porosidad , Ratas , Ratas Wistar , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Iron deficiency anemia (IDA) is prevalent, and intravenous iron, especially if given in a single dose, may result in better adherence compared with oral iron. The present trial (FERWON-IDA) is part of the FERWON program with iron isomaltoside 1000/ferric derisomaltose (IIM), evaluating safety and efficacy of high dose IIM in IDA patients of mixed etiologies. This was a randomized, open-label, comparative, multi-center trial conducted in the USA. The IDA patients were randomized 2:1 to a single dose of 1000 mg IIM, or iron sucrose (IS) administered as 200 mg intravenous injections, up to five times. The co-primary endpoints were adjudicated serious or severe hypersensitivity reactions, and change in hemoglobin from baseline to week eight. A total of 1512 patients were enrolled. The frequency of patients with serious or severe hypersensitivity reactions was 0.3% (95% confidence interval: 0.06;0.88) vs 0.4% (0.05;1.45) in the IIM and IS group, respectively. The co-primary safety objective was met, and no risk difference was observed between groups. The co-primary efficacy endpoint of non-inferiority in hemoglobin change was met, and IIM led to a significantly more rapid hematological response in the first two weeks. The frequency of cardiovascular events was 0.8% and 1.2% in the IIM and IS group, respectively (P = .570). The frequency of hypophosphatemia was low in both groups. Iron isomaltoside administered as 1000 mg resulted in a more rapid and more pronounced hematological response, compared with IS, which required multiple visits. The safety profile was similar with a low frequency of hypersensitivity reactions and cardiovascular events.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Disacáridos/administración & dosificación , Compuestos Férricos/administración & dosificación , Sacarato de Óxido Férrico/administración & dosificación , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/patología , Disacáridos/efectos adversos , Femenino , Compuestos Férricos/efectos adversos , Sacarato de Óxido Férrico/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Preoperative anemia affects 30-40% of patients undergoing major surgery and is an independent risk factor for perioperative blood transfusion, morbidity, and mortality. Absolute or functional iron deficiency is its leading cause. Nonanemic hematinic deficiencies are also prevalent and may hamper preoperative hemoglobin optimization and/or recovery from postoperative anemia. As modifiable risk factors, anemia and hematinic deficiencies should be detected and corrected prior to major surgical procedures. Postoperative anemia is even more common (up to 80-90%) due to surgery-associated blood loss, inflammation-induced blunted erythropoiesis, and/or preexisting anemia. Preoperative oral iron may have a role in mild-to-moderate anemia, provided there is sufficient time (6-8 weeks) and adequate tolerance of oral preparations. Postoperative oral iron is of little value and rife with gastrointestinal adverse events. Intravenous iron should preferentially be used in cases of moderate-to-severe iron deficiency anemia, concomitant use of erythropoiesis-stimulating agents, short time to surgery or nonelective procedures, and for postoperative anemia management. Minor infusion reactions to intravenous iron are rare, the incidence of severe anaphylactic reactions is extremely low, and there is no increase in infections with intravenous iron. Currently available intravenous iron formulations allowing administration of large single doses are preferred.
Asunto(s)
Anemia Ferropénica/prevención & control , Hierro/administración & dosificación , Anemia Ferropénica/epidemiología , Anemia Ferropénica/patología , Artroplastia de Reemplazo , Transfusión de Eritrocitos , Eritropoyetina/uso terapéutico , Enfermedades Gastrointestinales/etiología , Humanos , Hierro/efectos adversos , Atención PerioperativaRESUMEN
Anemia is frequently encountered in patients with inflammatory bowel disease (IBD), decreasing the quality of life and significantly worsening the prognosis of the disease. The pathogenesis of anemia in IBD is multifactorial and results mainly from intestinal blood loss in inflamed mucosa and impaired dietary iron absorption. Multiple studies have proposed the use of the polyphenolic compound curcumin to counteract IBD pathogenesis since it has significant preventive and therapeutic properties as an anti-inflammatory agent and very low toxicity, even at high dosages. However, curcumin has been shown to possess properties consistent with those of an iron-chelator, such as the ability to modulate proteins of iron metabolism and decrease spleen and liver iron content. Thus, this property may further contribute to the development and severity of anemia of inflammation and iron deficiency in IBD. Herein, we evaluate the effects of curcumin on systemic iron balance in the dextran sodium sulfate (DSS) model of colitis in C57Bl/6 and BALB/c mouse strains that were fed an iron-sufficient diet. In these conditions, curcumin supplementation caused mild anemia, lowered iron stores, worsened colitis and significantly decreased overall survival, independent of the mouse strain. These findings suggest that curcumin usage as an anti-inflammatory supplement should be accompanied by monitoring of erythroid parameters to avoid exacerbation of iron deficiency anemia in IBD.
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Anemia Ferropénica/inducido químicamente , Antiinflamatorios no Esteroideos/efectos adversos , Colitis/tratamiento farmacológico , Curcumina/efectos adversos , Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Colitis/inducido químicamente , Colitis/patología , Curcumina/uso terapéutico , Sulfato de Dextran , Femenino , Hierro de la Dieta/metabolismo , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
Iron deficiency anemia (IDA) is a common nutritional disease suffered by 1 billion people. To develop a new drug which avoids the side effects of traditional oral iron supplementation for IDA treatment, we have designed Fe3O4@ Astragalus polysaccharide core-shell nanoparticles (Fe3O4@APS NPs) and demonstrated them to be an efficient therapeutic drug for IDA treatment in vivo. The Fe3O4@APS NPs have been successfully synthesized with good water solubility and stability, especially in imitated digestion. Cytotoxicity assessment in cells and pathological tests in mice justify their good biocompatibility and low toxicity. The IDA treatment in rats shows that they have efficient therapeutic effect, which is contributed to both the iron element supplement from Fe3O4 and the APS-stimulated hematopoietic cell generation. Moreover, the superparamagnetic Fe3O4@APS NPs are capable for use as a magnetic resonance imaging contrast agent. This study presents the possibility of nanocomposites involving purified natural products from Chinese herb medicine for biomedical applications.
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Anemia Ferropénica/terapia , Óxido Ferrosoférrico/química , Polisacáridos/química , Anemia Ferropénica/patología , Anemia Ferropénica/veterinaria , Animales , Planta del Astrágalo/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/química , Estabilidad de Medicamentos , Humanos , Riñón/diagnóstico por imagen , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos ICR , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanopartículas/toxicidad , Ratas , Ratas Wistar , SolubilidadRESUMEN
Iron deficiency is present in ~50% of heart failure (HF) patients. Large multicenter trials have shown that treatment of iron deficiency with i.v. iron benefits HF patients, but the underlying mechanisms are not known. To investigate the actions of iron deficiency on the heart, mice were fed an iron-depleted diet, and some received i.v. ferric carboxymaltose (FCM), an iron supplementation used clinically. Iron-deficient animals became anemic and had reduced ventricular ejection fraction measured by magnetic resonance imaging. Ca2+ signaling, a pathway linked to the contractile deficit in failing hearts, was also significantly affected. Ventricular myocytes isolated from iron-deficient animals produced smaller Ca2+ transients from an elevated diastolic baseline but had unchanged sarcoplasmic reticulum (SR) Ca2+ load, trigger L-type Ca2+ current, or cytoplasmic Ca2+ buffering. Reduced fractional release from the SR was due to downregulated RyR2 channels, detected at protein and message levels. The constancy of diastolic SR Ca2+ load is explained by reduced RyR2 permeability in combination with right-shifted SERCA activity due to dephosphorylation of its regulator phospholamban. Supplementing iron levels with FCM restored normal Ca2+ signaling and ejection fraction. Thus, 2 Ca2+-handling proteins previously implicated in HF become functionally impaired in iron-deficiency anemia, but their activity is rescued by i.v. iron supplementation.
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Anemia Ferropénica/patología , Insuficiencia Cardíaca/etiología , Contracción Miocárdica , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Administración Intravenosa , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Anemia Ferropénica/tratamiento farmacológico , Animales , Calcio/metabolismo , Proteínas de Unión al Calcio/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Compuestos Férricos/administración & dosificación , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/prevención & control , Humanos , Hierro/sangre , Imagen por Resonancia Magnética , Masculino , Maltosa/administración & dosificación , Maltosa/análogos & derivados , Ratones , Miocardio/citología , Miocardio/patología , Miocitos Cardíacos , Cultivo Primario de Células , Retículo Sarcoplasmático/patología , Volumen SistólicoRESUMEN
INTRODUCTION: Anaemia in women during pregnancy and child bearing age is one of the most common global health problems. Reasons are numerous, but in many cases only minimal attempts are made to elucidate the underlying causes. In this study we aim to identify aetiology of anaemia in women of child bearing age and to determine the relative contributions, effects and interactions of α- and ß-thalassaemia in a region of the world where thalassaemia is endemic. METHODS: A cross sectional study was conducted at the Colombo North Teaching Hospital of Sri Lanka. The patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened to identify women with anaemia during pregnancy and 253 anaemic females were randomly re-called for the study. Data were collected using an interviewer-administered questionnaire and haematological investigations were done to identify aetiologies. RESULTS: Out of the 253 females who were anaemic during pregnancy and were re-called, 8 were excluded due to being currently pregnant. Of the remaining 245 females, 117(47.8%) remained anaemic and another 22(9.0%) had non-anaemic microcytosis. Of anaemic females, 28(24.8%) were iron deficient, 40(35.4%) had low-normal serum ferritin without fulfilling the criteria for iron deficiency,18(15.3%) had ß-haemoglobinopathy trait and 20(17.0%) had α-thalassaemia trait. Of females who had non-anaemic microcytosis, 14(66.0%) had α-thalassaemia trait. In 4 females, both α- and ß-thalassaemia trait coexist. These females had higher levels of haemoglobin (p = 0.06), MCV (p<0.05) and MCH (p<0.01) compared to individuals with only ß-thalassaemia trait. A significantly higher proportion of premature births (p<0.01) and lower mean birth weights (p<0.05) were observed in patients with α-thalassaemia trait. CONCLUSIONS: Nearly one third of anaemic females in child bearing age had thalassaemia trait of which α-thalassemia contributes to a majority. Both α- and ß-thalassaemia trait can co-exist and have ameliorating effects on red cell indices in heterozygous states. α-Thalassaemia trait was significantly associated with premature births and low birth weight. It is of paramount importance to investigate the causes of anaemia in women of child bearing age and during pregnancy in addition to providing universal iron supplementation.
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Anemia/genética , Deficiencias de Hierro , Talasemia alfa/genética , Talasemia beta/genética , Adulto , Anemia/sangre , Anemia/complicaciones , Anemia/dietoterapia , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Anemia Ferropénica/genética , Anemia Ferropénica/patología , Suplementos Dietéticos , Femenino , Ferritinas/sangre , Humanos , Recién Nacido de Bajo Peso , Hierro/sangre , Hierro/uso terapéutico , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/genética , Complicaciones Hematológicas del Embarazo/prevención & control , Nacimiento Prematuro/sangre , Nacimiento Prematuro/patología , Sri Lanka/epidemiología , Encuestas y Cuestionarios , Adulto Joven , Talasemia alfa/sangre , Talasemia alfa/complicaciones , Talasemia alfa/dietoterapia , Talasemia beta/sangre , Talasemia beta/complicaciones , Talasemia beta/dietoterapiaRESUMEN
BACKGROUND: The effect of maternal weights on the risk of iron deficiency anemia (IDA) during pregnancy remains unclear. The study aimed to investigate the association between maternal weight indicators and IDA during pregnancy. METHODS: We conducted a cohort study to examine the association between maternal weight indicators, including prepregnancy body mass index and the rate of gestational weight gain (GWG), and the risk of IDA among Chinese pregnant women. Data about new-onset IDA at different trimesters from a national cross-sectional survey were collected; information regarding baseline variables and rate of GWG from women participating in the survey were retrospectively collected. Tested IDA and reported IDA were documented. Multilevel logistic regression to examine the association between maternal weight indicators and the risk of IDA after adjusting for potential confounders was conducted. RESULTS: This study enrolled 11,782 pregnant women from 24 hospitals from September 19, 2016, to November 20, 2016. Among those, 1515 (12.9%) IDA events were diagnosed through test (test IDA); 3915 (33.3%) were identified through test and patient reporting (composite IDA). After adjusting for confounders and cluster effect of hospitals, underweight pregnant women, compared with normal women, were associated with higher risk of test IDA (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.17-1.57 and composite IDA (aOR: 1.35, 95% CI: 1.21-1.51); on the contrary, overweight and obese women had lower risk of test IDA (aOR: 0.68, 95% CI: 0.54-0.86 overweight; aOR: 0.30, 95% CI: 0.13-0.69 obese) and composite IDA (aOR: 0.77, 95% CI: 0.67-0.90 overweight; aOR: 0.34, 95% CI: 0.21-0.55 obese). The higher rate of GWG was associated with higher risk of IDA (test aOR: 1.86 95% CI: 1.26-2.76; composite aOR: 1.54, 95% CI: 1.16-2.03). CONCLUSIONS: Pregnant women who are underweight before pregnancy and who have faster GWG are more likely to develop IDA. Enforced weight control during pregnancy and use of iron supplements, particularly among underweight women, may be warranted.
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Anemia Ferropénica/metabolismo , Anemia Ferropénica/patología , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Estudios Transversales , Femenino , Ganancia de Peso Gestacional/fisiología , Humanos , Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: While iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis. METHODS: Maintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression. RESULTS: Among 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps. CONCLUSIONS: ID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis.
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Anemia Ferropénica/patología , Hemoglobinas/análisis , Fallo Renal Crónico/patología , Anciano , Anemia Ferropénica/etiología , Artralgia/etiología , Fatiga/etiología , Femenino , Ferritinas/sangre , Cefalea/etiología , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Diálisis Renal , Factores de Riesgo , Índice de Severidad de la Enfermedad , Transferrina/análisisRESUMEN
BACKGROUND: Previous studies have shown beneficial effects of dietary approaches for iron deficiency anemia (IDA) control. This study was design to investigate the effect of dietary intervention treatment on children with iron deficiency anemia. METHODS: We performed a systematic review of published dietary interventions effect on IDA treatment through meta-analysis. CBM, CNKI, Wanfang database, EMBASE, VIP, PubMed and Web of science database were searched to identify studies published between January, 1980 and December, 2016. Statistical analysis was performed by Revmen5.2 software. RESULTS: Initially we retrieved for 373 studies, and then 6 studies with a total of 676 individuals were included in the analysis according to the inclusion and exclusion criteria for meta-analysis. The overall pooled estimate of odds ratio [(OR), 95% confidence intervals (95% CI)] in the dietary intervention on children with iron deficiency anemia was 6.54 (95% CI: 3.48-12.31, Z = 5.82, p<0.001) and funnel plot is symmetric. CONCLUSIONS: Our meta-analysis suggested that dietary interventions are effective in improving the iron deficiency in children with iron deficiency anemia (IDA) and should be considered in the overall strategy of IDA management.
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Anemia Ferropénica/dietoterapia , Anemia Ferropénica/epidemiología , Dieta/métodos , Suplementos Dietéticos , Adolescente , Anemia Ferropénica/patología , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Lactante , MasculinoRESUMEN
INTRODUCTION: Bisphenol A (BPA) is suspected to cause hormonal imbalance in humans. Dietary factors are known to bring changes in hormonal profile. In order to study chemico-biological interaction of iron deficiency on toxicity outcome of BPA exposure, we studied the modulatory effects of iron deficiency on the hormone levels in rats chronically-exposed to BPA. METHODS: Weanling rats maintained on normal and iron-deficient diets were exposed to low level of BPA at 0, 1, 5 and 10 ppm for six months through drinking water. The serum levels of thyroidstimulating hormone (TSH), testosterone, progesterone and estradiol were measured in the animals by enzyme-linked immunosorbent assay kit. Histopathology was performed to check the pathological changes in gonads. RESULTS: No significant change was observed in TSH, progesterone and estradiol levels at 1 and 5 ppm BPA. However, at 10 ppm BPA a significant increase in TSH level was observed in the animals maintained on an iron-deficient diet of either sex. BPA caused a significant change in testosterone level even at 5 and 10 ppm doses in animals of either sex. However, in male rats 1 ppm dose also showed a significant effect in the animals maintained on iron deficient diet. Changes in the histoarchitecture of the testes at high dose of BPA (10 ppm) were more remarkable in anemic rats. CONCLUSION: These results suggest that iron deficiency has no generalized effect on hormonal levels in BPA-treated animals and trends indicate a more remarkable effect in male animals at hormonal and tissue levels.
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Anemia Ferropénica/sangre , Compuestos de Bencidrilo/toxicidad , Disruptores Endocrinos/toxicidad , Hormonas/sangre , Fenoles/toxicidad , Testículo/efectos de los fármacos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/patología , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Femenino , Masculino , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología , Progesterona/sangre , Ratas Wistar , Factores Sexuales , Testículo/metabolismo , Testículo/patología , Testosterona/sangre , Tirotropina/sangre , Factores de Tiempo , DesteteRESUMEN
Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated.