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1.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500637

RESUMO

The most common cause of iron deficiency is an improperly balanced diet, in which the body's need for iron cannot be met by absorption of this element from food. Targeted iron supplementation and food fortification may be the main treatments for iron deficiency in the population. However, many iron-rich supplements and foods have low bioavailability of this element. In our study, we used yeast enriched with iron ions to produce flatbread. The yeast cells accumulated iron ions from the medium supplemented with Fe(NO3)3·9H2O, additionally one of the cultures was treated with pulsed electric field in order to increase the accumulation. The potential bioavailability of iron from flatbread containing 385.8 ± 4.12 mg of iron in 100 g dry mass was 10.83 ± 0.94%. All the flatbreads had a moderate glycemic index. There were no significant differences in antioxidant activity against DPPH• between flatbread with iron-enriched and non-iron-enriched yeast. Sensory evaluation showed that this product is acceptable to consumers since no metallic aftertaste was detected. Iron enriched flatbread can potentially be an alternative to dietary supplements in iron deficiency states.


Assuntos
Pão/microbiologia , Suplementos Nutricionais/microbiologia , Alimentos Fortificados/microbiologia , Ferro/metabolismo , Saccharomyces cerevisiae/metabolismo , Anemia Ferropriva/metabolismo , Anemia Ferropriva/prevenção & controle , Antioxidantes/metabolismo , Disponibilidade Biológica , Índice Glicêmico/fisiologia , Humanos
2.
Am J Hematol ; 96(10): 1253-1263, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34343368

RESUMO

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.


Assuntos
Anemia Ferropriva/terapia , Compostos Férricos/uso terapêutico , Compostos Ferrosos/uso terapêutico , Compostos de Ferro/uso terapêutico , Ferro na Dieta/uso terapêutico , Administração Oral , Anemia Ferropriva/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Compostos Férricos/administração & dosagem , Compostos Ferrosos/administração & dosagem , Humanos , Ferro/metabolismo , Compostos de Ferro/administração & dosagem , Ferro na Dieta/administração & dosagem , Masculino , Camundongos
3.
Cells ; 10(8)2021 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-34440936

RESUMO

Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific criteria for the diagnosis of functional nutritional deficiency related to anemia are necessary. We examined the nationally representative sample of Polish seniors. Complete blood count, serum iron, ferritin, vitamin B12, folate, and renal parameters were assessed in 3452 (1632 women, 1820 men) participants aged above 64. Cut-off points for nutritional deficiencies were determined based on the WHO criteria (method-A), lower 2.5 percentile of the studied population (method-B), and receiver operating characteristic (ROC) analysis (method-C). Method-A leads to an overestimation of the prevalence of vitamin B12 and folate deficiency, while method-B to their underestimation with over 50% of unexplained anemia. Based on method-C, anemia was classified as nutritional in 55.9%. In 22.3% of cases, reasons for anemia remained unexplained, the other 21.8% were related to CKD or AI. Mild cases were less common in IDA, and more common in non-deficiency anemia. Serum folate had an insignificant impact on anemia. It is necessary to adopt the age-specific criteria for nutrient deficiency in an old population.


Assuntos
Anemia/etiologia , Anemia/metabolismo , Anemia Ferropriva/complicações , Anemia Ferropriva/metabolismo , Feminino , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/metabolismo , Humanos , Inflamação/complicações , Inflamação/metabolismo , Masculino , Polônia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/metabolismo
4.
Sci Rep ; 11(1): 13699, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211054

RESUMO

Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.


Assuntos
Anemia Ferropriva/complicações , Neoplasias Colorretais/complicações , Compostos Férricos/uso terapêutico , Compostos Ferrosos/uso terapêutico , Maltose/análogos & derivados , Administração Intravenosa , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/metabolismo , Anemia Ferropriva/terapia , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Feminino , Compostos Férricos/administração & dosagem , Compostos Ferrosos/administração & dosagem , Humanos , Ferro/metabolismo , Masculino , Maltose/administração & dosagem , Maltose/uso terapêutico , Pessoa de Meia-Idade
5.
Blood Coagul Fibrinolysis ; 32(7): 451-457, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34148983

RESUMO

Oxidative stress is a potential mechanism involved in the pathogenesis of iron deficiency anaemia (IDA). Although a tendency for hypercoagulability has been reported in IDA, its underlying mechanism is yet to be elucidated. This study investigated the probable relationship between oxidative stress and hypercoagulability in children with IDA. This study included 57 children diagnosed with IDA (IDA group) between October 2016 and October 2017 in addition to 48 healthy children (control group). The maximum clot firmness (MCF) index, and clot formation time (CFT) index, which are indicators of hypercoagulability in rotational thromboelastometry assays [intrinsic TEM (INTEM) and extrinsic TEM (EXTEM)] derived from our previous study, were recorded. Total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI) were analysed from serum samples of the individuals. In IDA group, OSI and TOS levels were higher and TAC level was lower compared to the control group (P < 0.001, for all). The EXTEM and INTEM MCF in the IDA group was higher than in the control group, while the INTEM CFT was lower than in the control group (P < 0.001, P < 0.001, P < 0.05, published data).TOS and OSI had a negative correlation with INTEM CFT (r:-0.361, P < 0.001 and r:-0.333, P = 0.001) and a positive correlation with INTEM MCF (r:+0.420, P < 0.001 and r:+0.367, P < 0.001) and EXTEM MCF (r:+0.476, P < 0.001 and r:+0.403, P < 0.001). However, TAC demonstrated no correlation with CFT and MCF index. The oxidant-antioxidant balance is disrupted in favour of oxidative stress in children with IDA. In addition, TOS and OSI, which are parameters of oxidative stress, are correlated with CFT and MCF indices. Oxidative stress appears to be an important factor for the development of tendency to hypercoagulability in IDA.


Assuntos
Anemia Ferropriva/complicações , Trombofilia/complicações , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/metabolismo , Coagulação Sanguínea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estresse Oxidativo , Trombofilia/sangue , Trombofilia/metabolismo
6.
Biochem Pharmacol ; 190: 114661, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157296

RESUMO

Iron deficiency and iron overload are the most prevalent and opposite forms of dysregulated iron metabolism that affect approximately 30 percent of the world population, in particularly, elderly and patients with chronic diseases. Both iron deficiency and overload are frequently observed in a wide range of cardiovascular diseases, contributing to the onset and progression of these diseases. One of the devastating seqeulae for iron overload is the induction of ferroptosis, a newly defined form of regulated cell death which heavily impacts cardiac function through ferroptotic cell death in cardiomyocytes. In this review, we will aim to evaluate iron deficiency and iron overload in cardiovascular diseases. We will summarize current therapeutic strategies to tackle iron deficiency and iron overload, major pitfalls of current studies, and future perspectives.


Assuntos
Anemia Ferropriva/metabolismo , Doenças Cardiovasculares/etiologia , Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Anemia Ferropriva/complicações , Doenças Cardiovasculares/metabolismo , Humanos , Sobrecarga de Ferro/complicações
7.
J Clin Invest ; 131(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060484

RESUMO

Iron plays an important role in mammalian physiological processes. It is a critical component for the function of many proteins, including enzymes that require heme and iron-sulfur clusters. However, excess iron is also detrimental because of its ability to catalyze the formation of reactive oxygen species. As a result, cellular and systemic iron levels are tightly regulated to prevent oxidative damage. Iron deficiency can lead to a number of pathological conditions, the most prominent being anemia. Iron deficiency should be corrected to improve adult patients' symptoms and to facilitate normal growth during fetal development and childhood. However, inappropriate use of intravenous iron in chronic conditions, such as cancer and heart failure, in the absence of clear iron deficiency can lead to unwanted side effects. Thus, this form of therapy should be reserved for certain patients who cannot tolerate oral iron and need rapid iron replenishment. Here, we will review cellular and systemic iron homeostasis and will discuss complications of iron deficiency.


Assuntos
Anemia Ferropriva , Insuficiência Cardíaca , Ferro , Neoplasias , Adulto , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/metabolismo , Animais , Criança , Doença Crônica , Desenvolvimento Fetal/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Ferro/metabolismo , Ferro/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Nutrients ; 13(3)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673530

RESUMO

Anemia is a frequent finding in children with celiac disease but the detailed pathophysiological mechanisms in the intestine remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been inconsistent. We investigated this issue by comparing immunohistochemical stainings of duodenal cytochrome B (DCYTB), divalent metal transporter 1 (DMT1), ferroportin, hephaestin and transferrin receptor 1 (TfR1) in duodenal biopsies between 27 children with celiac disease and duodenal atrophy, 10 celiac autoantibody-positive children with potential celiac disease and six autoantibody-negative control children. Twenty out of these 43 subjects had anemia. The expressions of the iron proteins were investigated with regard to saturation and the percentage of the stained area or stained membrane length of the enterocytes. The results showed the stained area of ferroportin to be increased and the saturation of hephaestin to be decreased in celiac disease patients compared with controls. There were no differences in the transporter protein expressions between anemic and non-anemic patients. The present results suggest an iron status-independent alteration of ferroportin and hephaestin proteins in children with histologically confirmed celiac disease.


Assuntos
Antígenos CD/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Doença Celíaca/metabolismo , Grupo dos Citocromos b/metabolismo , Proteínas de Membrana/metabolismo , Oxirredutases/metabolismo , Receptores da Transferrina/metabolismo , Fatores de Transcrição/metabolismo , Adolescente , Anemia Ferropriva/complicações , Anemia Ferropriva/metabolismo , Antígenos CD/genética , Proteínas de Transporte de Cátions/genética , Doença Celíaca/complicações , Criança , Pré-Escolar , Grupo dos Citocromos b/genética , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Proteínas de Membrana/genética , Oxirredutases/genética , Receptores da Transferrina/genética , Fatores de Transcrição/genética
9.
Sci Rep ; 11(1): 6309, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737646

RESUMO

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.


Assuntos
Anemia Ferropriva/sangue , Anemia/sangue , Hemoglobinas/genética , Ferro/metabolismo , Adulto , Anemia/genética , Anemia/metabolismo , Anemia/patologia , Anemia Ferropriva/genética , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Área Sob a Curva , Contagem de Células Sanguíneas , Parto Obstétrico , Feminino , Hemoglobinas/isolamento & purificação , Hemoglobinas/metabolismo , Humanos , Gravidez , Fatores de Risco
10.
Acta Physiol (Oxf) ; 232(2): e13650, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33749990

RESUMO

AIMS: Recent reports suggest that iron deficiency impacts both intestinal calcium and phosphate absorption, although the exact transport pathways and intestinal segment responsible have not been determined. Therefore, we aimed to systematically investigate the impact of iron deficiency on the cellular mechanisms of transcellular and paracellular calcium and phosphate transport in different regions of the rat small intestine. METHODS: Adult, male Sprague-Dawley rats were maintained on a control or iron-deficient diet for 2 weeks and changes in intestinal calcium and phosphate uptake were determined using the in situ intestinal loop technique. The circulating levels of the hormonal regulators of calcium and phosphate were determined by ELISA, while the expression of transcellular calcium and phosphate transporters, and intestinal claudins were determined using qPCR and western blotting. RESULTS: Diet-induced iron deficiency significantly increased calcium absorption in the duodenum but had no impact in the jejunum and ileum. In contrast, phosphate absorption was significantly inhibited in the duodenum and to a lesser extent the jejunum, but remained unchanged in the ileum. The changes in duodenal calcium and phosphate absorption in the iron-deficient animals were associated with increased claudin 2 and 3 mRNA and protein levels, while levels of parathyroid hormone, fibroblast growth factor-23 and 1,25-dihydroxy vitamin D3 were unchanged. CONCLUSION: We propose that iron deficiency alters calcium and phosphate transport in the duodenum. This occurs via changes to the paracellular pathway, whereby upregulation of claudin 2 increases calcium absorption and upregulation of claudin 3 inhibits phosphate absorption.


Assuntos
Anemia Ferropriva , Cálcio , Anemia Ferropriva/metabolismo , Animais , Cálcio/metabolismo , Dieta , Duodeno/metabolismo , Absorção Intestinal , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Fosfatos/metabolismo , Ratos , Ratos Sprague-Dawley
11.
J Nutr ; 151(5): 1073-1083, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33693820

RESUMO

BACKGROUND: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental responses to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. OBJECTIVES: To identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. METHODS: We used a real-time PCR-based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n = 3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron-adequate mice at E12.5 (n = 8 dams/diet). RESULTS: In female placentas, 6 genes, including transferrin receptor (Tfrc) and solute carrier family 11 member 2, were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. A proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron-responsive element (IRE)-containing mRNA were altered in abundance; ferritin and ferroportin 1 decreased, while TFRC increased in ID placentas. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. CONCLUSIONS: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.


Assuntos
Anemia Ferropriva/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Proteoma/metabolismo , Transcriptoma/fisiologia , Animais , Feminino , Regulação da Expressão Gênica , Ferro/metabolismo , Ferro/farmacologia , Camundongos , Ferroproteínas não Heme/genética , Ferroproteínas não Heme/metabolismo , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Front Immunol ; 12: 635899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777027

RESUMO

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.


Assuntos
Anemia Ferropriva/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/metabolismo , Ferro/metabolismo , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/imunologia , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/prevenção & controle , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Ferro/imunologia , Compostos de Ferro/uso terapêutico , Estresse Oxidativo , Evasão Tumoral , Microambiente Tumoral
13.
Mol Nutr Food Res ; 65(8): e2001018, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33599094

RESUMO

SCOPE: Iron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post-treatment with iron dextran and B vitamins (pID+Fe). METHODS AND RESULTS: Metabolomic profiling of urine and plasma is conducted with 1 H nuclear magnetic resonance (NMR) spectroscopy. Gut microbiota are characterized from rectal swabs by amplicon sequencing of the 16S rRNA gene. Urinary metabolic profiles of pID monkeys significantly differed from pID+Fe and continuously iron-sufficient controls (IS) with higher maltose and lower amounts of microbial-derived metabolites. Persistent differences in energy metabolism are apparent from the plasma metabolic phenotypes with greater reliance on anaerobic glycolysis in pID monkeys. Microbial profiling indicated higher abundances of Methanobrevibacter, Lachnobacterium, and Ruminococcus in pID monkeys and any history of ID resulted in a lower Prevotella abundance compared to the IS controls. CONCLUSIONS: Lingering metabolic and microbial effects are found after natural recovery from ID. These long-term biochemical derangements are not present in the pID+Fe animals emphasizing the importance of the early detection and treatment of early-life ID to ameliorate its chronic metabolic effects.


Assuntos
Anemia Ferropriva/metabolismo , Anemia Ferropriva/microbiologia , Microbioma Gastrointestinal/fisiologia , Complexo Ferro-Dextran/farmacologia , Anemia Ferropriva/tratamento farmacológico , Animais , Animais Recém-Nascidos , Análise Química do Sangue , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Macaca mulatta , Metaboloma , RNA Ribossômico 16S , Urina/química
14.
Br J Haematol ; 193(5): 882-893, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33316086

RESUMO

The discovery of hepcidin has provided a solid foundation for understanding the mechanisms of systemic iron homeostasis and the aetiologies of iron disorders. Hepcidin assures the balance of circulating and stored iron levels for multiple physiological processes including oxygen transport and erythropoiesis, while limiting the toxicity of excess iron. The liver is the major site where regulatory signals from iron, erythropoietic drive and inflammation are integrated to control hepcidin production. Pathologically, hepcidin dysregulation by genetic inactivation, ineffective erythropoiesis, or inflammation leads to diseases of iron deficiency or overload such as iron-refractory iron-deficiency anaemia, anaemia of inflammation, iron-loading anaemias and hereditary haemochromatosis. In the present review, we discuss recent insights into the molecular mechanisms governing hepcidin regulation, how these pathways are disrupted in iron disorders, and how this knowledge is being used to develop novel diagnostic and therapeutic strategies.


Assuntos
Anemia Ferropriva , Eritropoese , Hemocromatose , Hepcidinas , Fígado , Anemia Ferropriva/genética , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Anemia Ferropriva/fisiopatologia , Animais , Hemocromatose/genética , Hemocromatose/metabolismo , Hemocromatose/patologia , Hemocromatose/fisiopatologia , Hepcidinas/sangue , Hepcidinas/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia
15.
Hematol Oncol Stem Cell Ther ; 14(1): 41-50, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32446932

RESUMO

OBJECTIVE/BACKGROUND: Mutations in transmembrane protease serine 6 (TMPRSS6) gene induce high hepcidin level, which causes iron-refractory iron deficiency anemia (IRIDA) by preventing duodenal iron absorption. This study aims to identify the common genetic variations of the TMPRSS6 gene that affect iron levels among Saudi female patients with iron deficiency anemia (IDA). METHODS: All study participants were Saudi females (12-49 years old): 32 patients with IDA, 32 patients with IRIDA, and 34 healthy individuals comprising the control group. Hematological investigations, iron profile, serum hepcidin level, and TMPRSS6 gene transcription were determined. The TMPRSS6 gene was amplified, sequenced, and analyzed among all study participants. RESULTS: The mean hepcidin and TMPRSS6 RNA transcription levels in IDA and IRIDA groups were significantly lower than those in the control group. TMPRSS6 gene sequence analysis detected 41 variants: two in the 5' untranslated region (5'UTR), 17 in introns, and 22 in exons. Thirty-three variants were previously reported in the Single Nucleotide Polymorphism Database, and eight variants were novel; one novel variant was in 5'UTR (g.-2 T > G); five novel variants were detected in exons (p.W73X, p.D479N, p.E523K, p.L674L, and p.I799I). At the time of the sequence analysis of our samples, two variants-p.D479N and p.674L-were novel. However, these variants are present at a very low allele frequency in other populations (L674L, 0.00007761 and D479N, 0.000003980). CONCLUSION: This is the first study to investigate the genetic variants of TMPRSS6 gene in Saudi female patients with IDA. The generated data will serve as a reference for future studies on IDA in the Arab population.


Assuntos
Alelos , Anemia Ferropriva/genética , Frequência do Gene , Proteínas de Membrana/genética , Mutação de Sentido Incorreto , Mutação Puntual , Serina Endopeptidases/genética , Regiões 5' não Traduzidas , Adolescente , Adulto , Substituição de Aminoácidos , Anemia Ferropriva/metabolismo , Criança , Duodeno/metabolismo , Feminino , Humanos , Absorção Intestinal/genética , Ferro/metabolismo , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Arábia Saudita , Serina Endopeptidases/metabolismo
16.
Hematology Am Soc Hematol Educ Program ; 2020(1): 471-477, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275751

RESUMO

Iron-deficiency anemia (IDA) affects many infants in low- and middle-income countries (LMICs) and may impair cognitive development and adaptive immunity. Effective interventions to improve iron intakes for infants in LMICs are urgently needed. However, absorption of oral iron fortificants and supplements is low, usually <10%, and most of the iron passes into the colon unabsorbed. In randomized controlled trials, provision of iron to infants in LMICs adversely affects their gut microbiome and increases pathogenic Escherichia coli, gut inflammation, and diarrhea. To minimize these detrimental effects of iron, it is important to provide the lowest effective dosage and maximize fractional iron absorption. Prebiotic galacto-oligosaccharides and apo-lactoferrin may prove useful in iron formulations in LMICs because they increase absorption of fortificant iron and at the same time may mitigate the adverse effects of unabsorbed iron on the infant gut. Providing well-absorbed iron early in infancy may improve immune function. Recent data from a Kenyan birth cohort suggest IDA at the time of infant vaccination impairs the response to diphtheria, pertussis, and pneumococcus vaccines. A randomized trial follow-up study reported that providing iron to Kenyan infants at the time of measles vaccination increased antimeasles immunoglobulin G (IgG), seroconversion, and IgG avidity. Because IDA is so common among infants in LMICs and because the vaccine-preventable disease burden is so high, even if IDA only modestly reduces immunogenicity of vaccines, its prevention could have major benefits.


Assuntos
Anemia Ferropriva , Alimentos Fortificados , Microbioma Gastrointestinal , Ferro/uso terapêutico , Estado Nutricional , Anemia Ferropriva/epidemiologia , Anemia Ferropriva/metabolismo , Anemia Ferropriva/microbiologia , Anemia Ferropriva/terapia , Humanos , Lactente , Quênia/epidemiologia , Lactoferrina , Masculino , Prebióticos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Molecules ; 25(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153225

RESUMO

Patients with iron deficiency anaemia are treated with oral iron supplementation, which is known to cause gastrointestinal side effects by likely interacting with the gut microbiome. To better study this impact on the microbiome, we investigated oral iron-driven changes in volatile organic compounds (VOCs) in the faecal metabolome. Stool samples from patients with iron deficiency anaemia were collected pre- and post-treatment (n = 45 and 32, respectively). Faecal headspace gas analysis was performed by gas chromatography-mass spectrometry and the changes in VOCs determined. We found that the abundance of short-chain fatty acids and esters fell, while aldehydes increased, after treatment. These changes in pre- vs. post-iron VOCs resemble those reported when the gut is inflamed. Our study shows that iron changes the intestinal metabolome, we suggest by altering the structure of the gut microbial community.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/metabolismo , Mucosa Intestinal/metabolismo , Ferro/administração & dosagem , Metaboloma , Compostos Orgânicos Voláteis/metabolismo , Administração Oral , Idoso , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino
18.
Nutr Hosp ; 37(5): 1087-1090, 2020 Oct 21.
Artigo em Espanhol | MEDLINE | ID: mdl-32960642

RESUMO

Introduction: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.


Assuntos
Anemia Ferropriva/etiologia , Cirurgia Bariátrica , Compostos de Ferro/uso terapêutico , Adulto , Anemia Ferropriva/metabolismo , Anemia Ferropriva/terapia , Suplementos Nutricionais , Resistência a Medicamentos , Nutrição Enteral , Feminino , Humanos , Infusões Intravenosas , Ferro/sangue , Compostos de Ferro/administração & dosagem , Síndromes de Malabsorção/etiologia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/terapia , Gravidez
19.
Int J Mol Sci ; 21(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32972031

RESUMO

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.


Assuntos
Anemia Ferropriva , Infecções Bacterianas , Hepcidinas/metabolismo , Ferro/metabolismo , África , Anemia Ferropriva/complicações , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/metabolismo , Infecções Bacterianas/patologia , Criança , Feminino , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de Doença
20.
Diabetes Metab Syndr ; 14(6): 1837-1840, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32961516

RESUMO

BACKGROUND AND AIMS: Iron deficiency anaemia, although well reported in diabetic nephropathy, has not been well studied in type 2 diabetes patients in the absence of nephropathy. We studied the prevalence of anaemia and iron deficiency in type 2 diabetes patients without nephropathy. MATERIAL AND METHODS: A total of 89 patients were selected for this study. 24 h urine protein less than 500 mg was used as the criteria to rule out diabetic nephropathy. Complete hemogram, iron profile and high sensitivity C reactive protein (hs CRP) levels were performed in each patient.Functional iron deficiency (FID) was defined as serum ferritin more than 100 µg/l with serum transferrin less than 20% and total iron deficiency state was defined as serum ferritin less than 100 µg/l. RESULTS: Fifteen patients (16.8%)had anaemia out of which 13 had total iron deficiency and one each had functional iron deficiency and normal iron status respectively. Assessment of the iron status overall showed that 49 patients had TID (55.05%), 16 had FID (17.9%)and 24 (27.05%) had normal iron status. The hs-CRP was significantly higher in those with iron deficiency. CONCLUSIONS: The present study found a high prevalence of iron deficiency anaemia in type 2 diabetic patients even in the absence of nephropathy. Most of the diabetic subjects also displayed an iron deficiency state the cause of which needs further investigation.


Assuntos
Anemia Ferropriva/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/patologia , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Biomarcadores/análise , Glicemia/análise , Feminino , Ferritinas/metabolismo , Seguimentos , Hemoglobinas/análise , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico
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