RESUMO
Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive1,2. Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.
Assuntos
Adaptação Fisiológica , Hipóxia Celular , Condrócitos , Hemoglobinas , Humanos , Cartilagem Articular/citologia , Cartilagem Articular/metabolismo , Morte Celular , Hipóxia Celular/fisiologia , Condrócitos/metabolismo , Citoplasma/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Eritrócitos/metabolismo , Glicólise , Hemoglobinas/deficiência , Hemoglobinas/genética , Hemoglobinas/metabolismo , Oxigênio/metabolismoRESUMO
PURPOSE: Few studies have so far focused on the preoperative presence of venous thromboembolism (VTE) in lung cancer patients undergoing surgery. In this study, we investigated the prevalence and risk factors for preoperative deep venous thrombosis (DVT) in patients scheduled to undergo lung cancer surgery. METHODS: Between June 2013 and December 2018, 948 consecutive patients underwent lung cancer surgery in Kindai University Hospital. Four patients did not undergo screening for DVT; thus, 944 patients were enrolled in this study. Preoperatively, venous ultrasonography of the lower extremities was performed in patients deemed at risk for DVT, and the prevalence and risk factors for preoperative DVT were examined. RESULTS: Ninety-one patients (9.6%) were diagnosed with preoperative DVT, and postoperative symptomatic pulmonary thromboembolism occurred in one patient (0.11%). A multivariable logistic regression analysis demonstrated that female sex, age ≥ 72 years, history of VTE, a Wells score ≥ 2 points, chronic obstructive pulmonary disease (COPD), and lower hemoglobin levels were significantly associated with preoperative DVT. CONCLUSION: Female sex, age ≥ 72 years, history of VTE, Wells score ≥ 2 points, COPD, and lower hemoglobin levels were identified to be independent risk factors for preoperative DVT. Monitoring for these risk factors and management considering them should help improve the outcomes after lung cancer surgery.
Assuntos
Neoplasias Pulmonares/cirurgia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Fatores Etários , Idoso , Feminino , Hemoglobinas/deficiência , Humanos , Neoplasias Pulmonares/complicações , Masculino , Complicações Pós-Operatórias , Período Pré-Operatório , Prevalência , Doença Pulmonar Obstrutiva Crônica , Embolia Pulmonar , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento , Ultrassonografia , Trombose Venosa/diagnóstico por imagemRESUMO
Anemia is known to be associated with depression both in community and clinical populations. However, it is still unknown if this association depends or not on antidepressant intake. We investigated the respective association of depression and antidepressant intake with low hemoglobin level in a large community-based cohort. In 8640 volunteers aged 50 to 75 recruited between June 2008 and June 2012 in Paris (France), we assessed hemoglobin levels (g/dl), depressive symptoms and antidepressant intake. We examined the association of both depression and antidepressant intake with hemoglobin level, adjusting for numerous socio-demographic and health variables. We also assessed the association with specific antidepressant classes. Depression and antidepressant intake were independently associated with lower hemoglobin level (ß = -0.074; p = .05 and ß = -0.100; p = .02 respectively in the fully-adjusted model). Regarding antidepressant classes, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) intake were associated with lower hemoglobin level (ß = -0.11; p = .01). To conclude, both depression and antidepressant intake were associated with lower hemoglobin level. In particular, as SSRI or SNRIs intake was also related to lower hemoglobin level, these classes should be used with caution in depressed individuals at risk for anemia.
Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Hemoglobinas/deficiência , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Idoso , Anemia/complicações , Antidepressivos/classificação , Estudos Transversais , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long-term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Cumulative exposure to eculizumab was 28 518 patient-years (PY) (PNH, 21 016 PY; aHUS, 7502 PY). Seventy-six cases of meningococcal infection were reported (0·25/100 PY), including eight fatal PNH cases (0·03/100 PY). Susceptibility to meningococcal infections remained the key risk in patients receiving eculizumab. The meningococcal infection rate decreased over time; related mortality remained steady. The most commonly reported serious nonmeningococcal infections were pneumonia (11·8%); bacteraemia, sepsis and septic shock (11·1%); urinary tract infection (4·1%); staphylococcal infection (2·6%); and viral infection (2·5%). There were 434 reported cases of eculizumab exposure in pregnant women; of 260 cases with known outcomes, 70% resulted in live births. Reporting rates for solid tumours (≈0·6/100 PY) and haematological malignancies (≈0·74/100 PY) remained stable over time. No new safety signals affecting the eculizumab benefit-risk profile were identified. Continued awareness and implementation of risk mitigation protocols are essential to minimise risk of meningococcal and other Neisseria infections in patients receiving eculizumab.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/efeitos adversos , Hemoglobinúria Paroxística/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Pré-Escolar , Inativadores do Complemento/uso terapêutico , Bases de Dados Factuais , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Hemoglobinas/deficiência , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Meningocócicas/induzido quimicamente , Pessoa de Meia-Idade , Infecções Oportunistas/induzido quimicamente , Farmacovigilância , Gravidez , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Adulto JovemRESUMO
Intravascular sickling and lysis of red blood cells, a hallmark feature of sickle cell disease (SCD), releases hemoglobin (Hb) into the circulation. Increased cell-free Hb has been linked to vasculopathy and in vitro lipid oxidation. Scavenger plasma proteins haptoglobin (Hp) and hemopexin (Hpx) can attenuate cell-free Hb and total plasma heme lipid-oxidative capacity but are depleted in SCD. Here, we isolated lipids from BERK-SS mice, guinea pigs (GP) infused with heme-albumin, and patients with SCD undergoing regular exchange transfusion therapy and evaluated the level of lipid oxidation. Malondialdehyde formation, an end product of lipid peroxidation, was increased in BERK-SS mice, purified lipid fractions of the heme-albumin infused GP, and patients with SCD compared with controls. In humans, the extent of lipid oxidation was associated with the absence of Hp as well as decreased Hpx in plasma samples. Postmortem pulmonary tissue obtained from patients with SCD demonstrated oxidized LDL deposition in the pulmonary artery. The relationship between no Hp and low Hpx levels with greater LDL and HDL oxidation demonstrates the loss of protection against cell-free Hb and total plasma heme-mediated lipid oxidation and tissue injury in SCD. Strategies to protect against plasma lipid oxidation by cell-free Hb and total plasma heme (e.g., therapeutic Hp and Hpx replacement) may diminish the deleterious effects of cell-free Hb and total plasma heme toward the vascular system in SCD.
Assuntos
Anemia Falciforme/fisiopatologia , Haptoglobinas/metabolismo , Hemoglobinas/deficiência , Hemopexina/deficiência , Lipídeos/química , Lipoproteínas/química , Adulto , Animais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Cobaias , Heme/química , Humanos , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Oxirredução , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed whether 30 AG-positive RAS/BD (AG+RAS/BD) patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than 33 AG-negative RAS/BD (AGÖ¾RAS/BD) patients or 126 age- and sex-matched healthy control subjects. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations were measured and compared among 30 AG+RAS/BD patients, 33 AGÖ¾RAS/BD patients, and 126 healthy control subjects. RESULTS: We found that 43.3%, 33.3%, 13.3%, 6.7%, and 20.0% of 30 AG+RAS/BD patients and 18.2%, 36.4%, 0%, 6.1%, and 9.1% of 33 AGÖ¾RAS/BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively. Moreover, 30 AG+RAS/BD patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects (all P-values < 0.05), and had a higher frequency of hemoglobin deficiency (P = 0.058, marginal significance) and a significantly higher frequency of vitamin B12 deficiency (P = 0.046) than 33 AGÖ¾RAS/BD patients. In addition, the 33 AGÖ¾RAS/BD patients had significantly higher frequencies of hemoglobin and iron deficiencies than healthy control subjects (both P-values < 0.001). CONCLUSION: We conclude that AG+RAS/BD patients do have significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects and have significantly higher frequencies of hemoglobin and vitamin B12 deficiencies than AGÖ¾RAS/BD patients.
Assuntos
Síndrome de Behçet/complicações , Deficiência de Ácido Fólico/complicações , Hemoglobinas/deficiência , Hiper-Homocisteinemia/complicações , Deficiências de Ferro , Deficiência de Vitamina B 12/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Síndrome de Behçet/sangue , Estudos de Casos e Controles , Feminino , Ácido Fólico/sangue , Glossite , Hemoglobinas/análise , Homocisteína/sangue , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Estomatite Aftosa , Taiwan , Vitamina B 12/sangue , Adulto JovemRESUMO
Chronic infection with the hepatitis C virus (HCV) affects 170 million people worldwide and is an important cause of liver-related morbidity and mortality. The standard of care therapy combines pegylated interferon (pegIFN) alpha and ribavirin (RBV), and is associated with a range of treatment-limiting adverse effects. One of the most important of these is RBV-induced haemolytic anaemia, which affects most patients and is severe enough to require dose modification in up to 15% of patients. Here we show that genetic variants leading to inosine triphosphatase deficiency, a condition not thought to be clinically important, protect against haemolytic anaemia in hepatitis-C-infected patients receiving RBV.
Assuntos
Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/genética , Variação Genética/genética , Hepatite C Crônica/tratamento farmacológico , Pirofosfatases/genética , Alelos , Anemia Hemolítica/complicações , Antivirais , Cromossomos Humanos Par 20 , Europa (Continente)/etnologia , Estudo de Associação Genômica Ampla , Hemoglobinas/deficiência , Hemoglobinas/metabolismo , Hepatite C Crônica/complicações , Humanos , Polimorfismo de Nucleotídeo Único/genética , Pirofosfatases/deficiência , Pirofosfatases/metabolismo , Grupos Raciais/genética , Ribavirina/uso terapêutico , Estados Unidos , Inosina TrifosfataseRESUMO
Recent findings made by our group indicate that the iron content in Phaseolus vulgaris leaves is at least four times greater than in grains therefore, we evaluated the effect of supplementation with bean leaf (iron content of 275 mg/kg on a dry basis) in iron-deficient rats. Anemia was induced by feeding rats with an iron-deficient diet (IDD) for 11 days and iron-recovery diets were subsequently tested for 14 days using a normal diet, a 10 % bean leaf-supplemented IDD (BLSD) or a ferrous sulfate-supplemented IDD. Decreased levels of leukocytes (64 %), erythrocytes (30 %), lymphocytes (62 %), granulocytes (72 %), hematocrit (34 %), hemoglobin (35 %), and ferritin (34 %) were observed in the iron-deficient rats compared to the control rats. BLSD supplementation showed the highest recovery values relative to those recorded for control rats: leukocytes (40 %), erythrocytes (24 %), lymphocytes (33 %), granulocytes (88 %), hematocrit (17 %), and hemoglobin (18 %), suggesting that common bean leaves could be a good source of bioavailable iron with possible immunomodulatory effects.
Assuntos
Ferro da Dieta/análise , Phaseolus/química , Folhas de Planta/química , Anemia Ferropriva/sangue , Anemia Ferropriva/prevenção & controle , Animais , Biomarcadores/sangue , Suplementos Nutricionais , Modelos Animais de Doenças , Eritrócitos/metabolismo , Feminino , Ferritinas/sangue , Ferritinas/deficiência , Compostos Ferrosos/administração & dosagem , Granulócitos/metabolismo , Hematócrito , Hemoglobinas/deficiência , Hemoglobinas/metabolismo , Ferro da Dieta/administração & dosagem , Leucócitos/metabolismo , Linfócitos/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: A portion of patients with recurrent aphthous stomatitis (RAS) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high blood homocysteine level with RAS. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 273 RAS patients were measured and compared with the corresponding levels in 273 age- and sex-matched healthy control subjects. RESULTS: We found that 57 (20.9%), 55 (20.1%), 13 (4.8%), and 7 (2.6%) RAS patients had deficiencies of hemoglobin (Men < 13 g/dl, Women < 12 g/dl), iron (<60 µg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 21 (7.7%) RAS patients had abnormally high blood homocysteine level. RAS patients had a significantly higher frequency of hemoglobin, iron, vitamin B12, or folic acid deficiency and of abnormally elevated blood homocysteine level than healthy control subjects (all P-values = 0.000 except for folic acid P = 0.022). If 273 RAS patients were further divided into 32 patients with major-typed RAS (MjRAS) and 241 patients with minor-typed RAS (MiRAS), we found that male MjRAS patients had a significantly lower mean hemoglobin concentration than MiRAS patients (P = 0.021), but MjRAS patients had a significantly higher mean homocysteine level than MiRAS patients (P = 0.000). CONCLUSION: We conclude that there is a significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and abnormally high blood homocysteine level with RAS.
Assuntos
Anemia Ferropriva/sangue , Deficiência de Ácido Fólico/sangue , Hemoglobinas/deficiência , Homocisteína/sangue , Estomatite Aftosa/sangue , Deficiência de Vitamina B 12/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND/PURPOSE: A portion of patients with oral lichen planus (OLP) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin (Hb), iron, vitamin B12, and folic acid and high blood homocysteine level with OLP. METHODS: The blood Hb, iron, vitamin B12, folic acid, and homocysteine concentrations in 352 OLP patients were measured and compared with the corresponding levels in 352 age- and sex-matched healthy control participants. RESULTS: We found that 77 (21.9%) OLP patients, 48 (13.6%) OLP patients, 25 (7.1%) OLP patients, and one (0.3%) OLP patient had deficiencies of Hb (men < 13 g/dL, women < 12 g/dL), iron (< 60 µg/dL), vitamin B12 (< 200 pg/mL), and folic acid (< 4 ng/mL), respectively. Moreover, 52 (14.8%) OLP patients had abnormally high blood homocysteine level. OLP patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally elevated blood homocysteine level than healthy control participants (all p < 0.001). Upon further dividing OLP patients into those with major erosive OLP (MjEOLP; n = 67), minor erosive OLP (n = 202), and nonerosive OLP (NEOLP; n = 83), we found that MjEOLP patients had a significantly higher mean homocysteine level than NEOLP patients (p = 0.035). CONCLUSION: We conclude that there is a significant association of deficiencies of Hb, iron, folic acid, and vitamin B12 and abnormally high blood homocysteine level with OLP. There may be a close relation of high blood homocysteine level to severity of OLP.
Assuntos
Deficiência de Ácido Fólico/epidemiologia , Hemoglobinas/análise , Homocisteína/sangue , Ferro/sangue , Líquen Plano Bucal/epidemiologia , Deficiência de Vitamina B 12/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Ácido Fólico/sangue , Hemoglobinas/deficiência , Humanos , Deficiências de Ferro , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Taiwan , Vitamina B 12/sangue , Adulto JovemRESUMO
BACKGROUND: Chronic kidney disease is a common comorbidity in elderly patients with heart failure. Evidence supports the use of angiotensin inhibitors for patients with heart failure. However, there is little evidence with which to assess the risk and benefits of this treatment in elderly patients with renal dysfunction. OBJECTIVE: To determine the efficacy and safety of angiotensin inhibitor reduction in patients with heart failure, chronic kidney disease and anaemia. STUDY DESIGN: Open randomized controlled clinical trial. SETTING: Complexo Hospitalario Universitario A Coruña (Spain). PATIENTS: Patients ≥ 50 years old, with heart failure, haemoglobin (Hb) < 12 mg/dl and creatinine clearance <60 ml/min/1.73 m(2) admitted to hospital, in treatment with angiotensin inhibitors. Informed consent and Ethical Review Board approval were obtained. INTERVENTION: A 50% reduction of angiotensin inhibitor dose of the basal treatment on admission (n = 30) in the intervention group. Control group (n = 16) with the standard basal dose. MAIN OUTCOME MEASURE: Primary outcome was difference in Hb (gr/dl), creatinine clearance (ml/min/1.73 m(2) ) and protein C (mg/dl) between admission and 1-3 months after discharge. Secondary outcome was survival at 6-12 months after discharge. RESULTS: Patients in the intervention group experienced an improvement in Hb (10.62-11.47 g/dl), creatinine clearance (32.5 ml/min/1.73 m(2) to 42.9 ml/min/1.73 m(2) ), and a decrease in creatinine levels (1.98-1.68 mg/dl) and protein C (3.23 mg/dl to 1.37 mg/dl). There were no significant differences in these variables in the control group. Survival at 6 and 12 months in the intervention and control group was 86.7% vs. 75% and 69.3% vs. 50%, respectively. CONCLUSION: The reduction of the dose of angiotensin inhibitors in the intervention group resulted in an improvement in anaemia and kidney function, decreased protein C and an increased survival rate. TRIAL REGISTRATION: EudraCT: 2008-008480-10.
Assuntos
Anemia/complicações , Antagonistas de Receptores de Angiotensina/administração & dosagem , Creatinina/urina , Insuficiência Cardíaca/complicações , Hemoglobinas/deficiência , Insuficiência Renal Crônica/complicações , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , EspanhaRESUMO
BACKGROUND/PURPOSE: Autoimmune thyroiditis can be diagnosed by measuring patients' serum levels of thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA). This study evaluated whether there were hematinic deficiencies, high blood homocysteine levels, and serum gastric parietal cell antibody (GPCA) positivity in patients with TGA or TMA. METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, homocysteine and TSH concentrations and the serum GPCA level in 190 TGA- or TMA-positive patients were measured and compared with the corresponding levels in 190 age- and sex-matched healthy control subjects. RESULTS: We found that 31 (16.3%), 27 (14.2%), 12 (6.3%), and 2 (1.1%) TGA- or TMA-positive patients had deficiencies of Hb (Men<13g/dL, Women<12g/dL), iron (< 60µg/dL), vitamin B12 (< 200pg/mL), and folic acid (< 4ng/mL), respectively. Moreover, 25 (13.2%) and 48 (25.3%) TGA- or TMA-positive patients had abnormally high blood homocysteine level and serum GPCA positivity, respectively. TGA- or TMA-positive patients had a significantly higher frequency of Hb (p<0.001), iron (p<0.001), or vitamin B12 deficiency (p=0.001), of abnormally elevated blood homocysteine level (p=0.001), or of serum GPCA positivity (p<0.001) than healthy control subjects. Of 190 TGA- or TMA-positive patients, 8 (4.2%) had lower serum TSH level (< 0.1µIU/mL, suggestive of hyperthyroidism), 163 (85.8%) had serum TSH level within normal range (0.1-4.5µIU/mL), and 19 (10%) had higher serum TSH level (>4.5µIU/mL, suggestive of hypothyroidis). CONCLUSION: There are significant deficiencies of hemoglobin, iron, and vitamin B12, abnormally high blood homocysteine levels, and serum GPCA positivity in TGA- or TMA-positive patients. In addition, the majority (85.8%) of TGA- or TMA-positive patients had euthyroid and only a small portion (14.2%) of TGA- or TMA-positive patients had either hypothyroidism or hyperthyroidism.
Assuntos
Deficiência de Ácido Fólico/etiologia , Hemoglobinas/deficiência , Homocisteína/sangue , Deficiências de Ferro , Tireoidite Autoimune/complicações , Deficiência de Vitamina B 12/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/diagnóstico , Hemoglobinas/metabolismo , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Hipertireoidismo/etiologia , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/etiologia , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Células Parietais Gástricas/imunologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnósticoRESUMO
Hemoglobin deficit (hbd) mice carry a spontaneous mutation that impairs erythroid iron assimilation but does not cause other defects. Normal delivery of iron to developing erythroid precursors is highly dependent on the transferrin cycle. Through genetic mapping and complementation experiments, we show that the hbd mutation is an in-frame deletion of a conserved exon of the mouse gene Sec15l1, encoding one of two Sec15 proteins implicated in the mammalian exocyst complex. Sec15l1 is linked to the transferrin cycle through its interaction with Rab11, a GTPase involved in vesicular trafficking. We propose that inactivation of Sec15l1 alters recycling of transferrin cycle endosomes and increases the release of transferrin receptor exocytic vesicles. This in turn decreases erythroid iron uptake. Determining the molecular basis of the hbd phenotype provides new insight into the intricate mechanisms necessary for normal erythroid iron uptake and the function of a mammalian exocyst protein.
Assuntos
Anemia/genética , Proteínas de Ligação ao GTP/genética , Hemoglobinas/deficiência , Proteínas de Membrana/genética , Mutação/genética , Animais , Transplante de Medula Óssea , Endossomos/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Teste de Complementação Genética , Hemoglobinas/genética , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Dados de Sequência Molecular , Mutagênese Insercional , Receptores da Transferrina/metabolismo , Retroviridae/genética , Deleção de Sequência , Transferrina/metabolismo , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Increased zinc protoporphyrin (ZPP) levels can indicate iron deficiency and may be predictive for low hemoglobin (Hb) deferral in blood donors. Prediction models for Hb deferral in whole blood donors have already been developed. In this study, we examined if addition of ZPP to these prediction models improves risk estimation of Hb deferral. STUDY DESIGN AND METHODS: This study included 4598 Dutch whole blood donors. Information on ZPP levels measured at the previous visit was added to the existing prediction models to estimate the risk of Hb deferral. Models were compared using the following measures: concordance (c)-statistic, continuous net reclassification improvement (NRI), and clinical net benefit (NB). RESULTS: Seventy-six male donors (2.9%) and 69 female donors (3.5%) were deferred because of a low Hb level. Previous ZPP level was associated with risk of Hb deferral (odds ratio for interquartile range of previous ZPP level, men 2.0 [95% confidence interval {CI}, 1.7-2.3]; women 2.2 [95% CI, 1.9-2.4]) in a multivariable risk model. Addition of ZPP into the models resulted in an increase of the c-statistic from 0.93 to 0.94 for men and from 0.80 to 0.85 for women. The added value of ZPP was confirmed by measures of clinical usefulness. NRI for men was 0.42, and for women, 0.56. At relevant threshold probabilities between 10 and 15%, NB was higher for models considering ZPP. CONCLUSION: This study shows that ZPP measurements obtained at the previous visit may have added value in the risk prediction of Hb deferral in whole blood donors.
Assuntos
Doadores de Sangue , Técnicas de Apoio para a Decisão , Seleção do Doador/métodos , Hemoglobinas/deficiência , Protoporfirinas/sangue , Adulto , Biomarcadores/sangue , Estudos de Coortes , Feminino , Hemoglobinas/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Medição de RiscoRESUMO
BACKGROUND: Atrophic glossitis (AG) is considered to be a marker of nutritional deficiency. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin, iron, vitamin B12 or folic acid, high blood homocysteine level, and serum gastric parietal cell antibody (GPCA) positivity with AG. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level in 176 AG patients were measured and compared with the corresponding levels in 176 age- and sex-matched healthy control subjects. RESULTS: We found that 39 (22.2%), 47 (26.7%), 13 (7.4%), and 3 (1.7%) AG patients had deficiencies of Hb (men < 13 g/dl, women < 12 g/dl), iron (<60 µg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 38 (21.6%) AG patients had abnormally high blood homocysteine level, and 47 (26.7%) AG patients had serum GPCA positivity. AG patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, or of serum GPCA positivity than healthy control subjects (all P-values = 0.000). However, no significant difference in frequency of folic acid deficiency was found between AG patients and healthy control subjects. CONCLUSION: We conclude that there is a significant association of deficiency of hemoglobin, iron and vitamin B12, abnormally high blood homocysteine level, and serum GPCA positivity with AG.
Assuntos
Anticorpos/sangue , Glossite/sangue , Hemoglobinas/deficiência , Hiper-Homocisteinemia/sangue , Deficiências de Ferro , Células Parietais Gástricas/imunologia , Deficiência de Vitamina B 12/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Síndrome da Ardência Bucal/complicações , Candidíase Bucal/complicações , Estudos de Casos e Controles , Feminino , Deficiência de Ácido Fólico/sangue , Humanos , Hipestesia/complicações , Masculino , Pessoa de Meia-Idade , Distúrbios do Paladar/complicações , Língua/irrigação sanguínea , Doenças da Língua/complicações , Doenças da Língua/microbiologia , Varizes/complicações , Xerostomia/complicaçõesRESUMO
OBJECTIVE: Assess the efficacy of a 10-week consumption of guava juice on the iron status of children with mild iron deficiency anemia. METHODS: Ninety-five boarding school children aged 6-9 years identified as anemic were randomly allocated to receive 300 mL of natural guava juice containing â¼200 mg of ascorbic acid (AA) or placebo (guava-flavored juice free of AA) with the main meal (5 d/wk). Information about dietary intake was collected at weeks 3, 5, and 7 at school and household levels. Changes in hemoglobin (Hb) and plasma ferritin (PF) among the subsample iron deficient at baseline (n = 33) were the main outcomes. RESULTS: Iron and phytic acid intakes at school and at home did not differ between groups. Baseline Hb and PF were 11.9 ± 0.5 g/dL and 8.2 ± 3.6 ng/mL for the guava, and 11.4 ± 1.1 g/dL and 7.4 ± 4.6 ng/mL for the placebo group (Hb: p = 0.08; PF: p = 0.31); at week 10 of the study, corresponding values were 13.1 ± 0.9 g/dL and 17.9 ± 10.3 ng/mL (n = 16), and 12.3 ± 1.3 g/dL and 15.4 ± 5.8 ng/mL (n = 12) (Hb: p = 0.05; PF: p = 0.21). With analysis of variance (ANOVA) for repeated measures, the guava group had 0.64 g/dL higher Hb (CI(95), 0.18-1.11; p = 0.01) and 2.47 ng/mL higher PF (CI(95), -1.04 to 5.98; p = 0.12) compared with the placebo group. CONCLUSION: Guava juice providing 200 mg AA at one meal on each school day had a marginal effect on Hb and PF concentrations in children consuming high-phytate diets fortified with iron.
Assuntos
Anemia Ferropriva/dietoterapia , Anemia Ferropriva/epidemiologia , Ácido Ascórbico/administração & dosagem , Bebidas , Psidium , Criança , Dieta , Ingestão de Energia , Feminino , Ferritinas/sangue , Ferritinas/deficiência , Hemoglobinas/análise , Hemoglobinas/deficiência , Humanos , Entrevistas como Assunto , Ferro da Dieta/administração & dosagem , Masculino , México/epidemiologia , Estado Nutricional , Ácido Fítico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Anemia remains a significant public health problem in refugee settings. Home fortification with micronutrient powders has been proposed as a feasible option to alleviate micronutrient deficiencies; its efficacy in reducing anemia in children aged 6 to 24 months has been demonstrated in several trials. OBJECTIVE: To evaluate the effectiveness of a large-scale micronutrient powder distribution program in reducing anemia prevalence and promoting growth in refugee children aged 6 to 59 months. METHODS: Four representative cross-sectional surveys were conducted 13 months before and 7, 14, and 26 months after initiation of the supplementation program. Data collected on children aged 6 to 59 months included hemoglobin concentration, anthropometric indicators, morbidity, feeding practices, and information on the micronutrient distribution program. The study had a pre-post design with no control group. RESULTS: The overall prevalence of anemia in children did not change significantly between baseline (43.3%) and endpoint (40.2%). The prevalence of moderate anemia decreased over the same period from 18.9% to 14.4% (p < .05). The levels of severe anemia were negligible (< 1%) in all surveys. The prevalence of stunting decreased significantly from 39.2% at baseline to 23.4% at endpoint (p < .001), a relative decrease of40%. Reported coverage, use, and acceptance of micronutrient supplements remained consistently high throughout the study. CONCLUSIONS: In the absence of a control group, changes in key outcomes should be interpreted with caution. The minor effect on hemoglobin status requires further investigation of underlying causes of anemia in this population. The large positive effect on linear growth may be a significant benefit of supplementation if confirmed by future studies.
Assuntos
Anemia Ferropriva/epidemiologia , Comportamento Alimentar , Alimentos Fortificados , Desnutrição/epidemiologia , Micronutrientes/administração & dosagem , Refugiados , Anemia Ferropriva/prevenção & controle , Antropometria , Butão/epidemiologia , Pré-Escolar , Estudos Transversais , Feminino , Hemoglobinas/análise , Hemoglobinas/deficiência , Humanos , Lactente , Entrevistas como Assunto , Masculino , Inquéritos Nutricionais , Necessidades Nutricionais , Estado Nutricional , Prevalência , Saúde Pública , OligoelementosRESUMO
BACKGROUND: Micronutrient powder has been endorsed as an effective means to improve the micronutrient status of emergency-affected populations. OBJECTIVE: To document the experience and findings of a cross-sectional assessment of the micronutrient powder program implemented as part of the emergency response to Cyclone Sidr. METHODS: Micronutrient powder was distributed to 100,714 children under 5 years of age and 59,439 pregnant or lactating women severely affected by Cyclone Sidr in Bangladesh. A cross-sectional assessment, including hemoglobin and anthropometric measurements, was conducted after the completion of the micronutrient powder program among children under 5 years of age, lactating mothers, and postmenarcheal adolescent girls in the intervention area. Comparison groups for each, drawn from the control area, which had not received micronutrient powder, were assessed at the same time. RESULTS: The prevalence of anemia among children under 5 years of age was approximately 80% in both areas. Among children in the intervention area, those who consumed at least 75% of the micronutrient powder sachets had a lower prevalence of stunting than those who consumed less than 75% of the sachets (40% vs. 52%, p < .05). Among lactating mothers in the intervention area, the prevalence rates of thinness and anemia were lower among those who consumed at least 75% of the sachets than among those who consumed less than 75% of the sachets (thinness, 31% vs. 46%, p < .05; anemia, 50% vs. 61%, p = .07). For adolescent girls in the intervention and control areas, none of whom had received micronutrient powder, the prevalence rates of anemia were 52% and 45%, respectively (p = .05). CONCLUSIONS: Micronutrient powder may reduce anemia among lactating mothers, when the compliance rate is high. Anemia prevalence prior to micronutrient powder distribution had not been investigated and could have been higher among children and lactating mothers in the intervention than in the control area, resulting in the negation of the potential positive impact of micronutrient powder on anemia.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/epidemiologia , Micronutrientes/administração & dosagem , Oligoelementos/administração & dosagem , Adolescente , Adulto , Antropometria , Bangladesh , Pré-Escolar , Estudos Transversais , Tempestades Ciclônicas , Suplementos Nutricionais , Desastres , Feminino , Serviços de Alimentação , Hemoglobinas/deficiência , Humanos , Lactente , Entrevistas como Assunto , Lactação , Masculino , Micronutrientes/deficiência , Mães , Estado Nutricional , Gravidez , Prevalência , Fatores Socioeconômicos , Oligoelementos/deficiência , Adulto JovemRESUMO
BACKGROUND: Micronutrient powder is a potential strategy to improve iron status and reduce anemia in refugee populations. OBJECTIVE: To evaluate the effect of the availability of home fortification with a micronutrient powder containing 2.5 mg of sodium iron ethylenediaminetetraacetate (NaFeEDTA) on iron status and hemoglobin in women and children in the Kakuma Refugee Camp in northwest Kenya. METHODS: Hemoglobin and soluble transferrin receptor were measured in 410 children 6 to 59 months of age and 458 women of childbearing age at baseline (just before micronutrient powder was distributed, along with the regular food ration) and at midline (6 months) and endline (13 months)follow-up visits. RESULTS: At the baseline, midline, and endline visits, respectively, the mean (+/- SE) hemoglobin concentration in women was 121.4 +/- 0.8, 120.8 +/- 0.9, and 120.6 +/- 1.0 g/L (p = .42); the prevalence of anemia (hemoglobin < 120 g/L) was 42.6%, 41.3%, and 41.7% (p = .92); and the mean soluble transferrin receptor concentration was 24.1 +/- 0.5, 20.7 +/- 0.7, and 20.8 +/- 0.7 nmol/L (p = .0006). In children, the mean hemoglobin concentration was 105.7 +/- 0.6, 109.0 30322 1.5, and 105.5 +/- 0.3 g/L (p = .95), respectively; the prevalence of anemia (hemoglobin < 110 g/L) was 55.5%, 52.3%, and 59.8% (p = .26); and the mean soluble transferrin receptor concentration was 36.1 +/- 0.7, 29.5 +/- 1.9, and 28.4 +/- 3.2 nmol/L (p = .02), in models that were adjusted for age using least squares means regression. CONCLUSIONS: In children and in women of childbearing age, the availability of micronutrient powder was associated with a small improvement in iron status but no significant change in hemoglobin in this refugee camp setting.