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1.
Mitochondrial ferritin expression in erythroid cells from patients with alpha-thalassaemia.
Putburee, R, Jetsrisuparb, A, Fucharoen, S, Tripatara, A
Hematology (Amsterdam, Netherlands). 2018;(10):844-848
Abstract
BACKGROUND Patients with thalassaemia who received regular transfusions had increased iron accumulation, leading to iron overload, which was associated with oxidative stress. Mitochondrial ferritin, encoded by the FTMT gene is an iron-storage protein in the mitochondria. The aim of this work was to investigate the expression levels of FTMT in the reticulocytes of patients with alpha-thalassaemia who were regularly transfused and rarely transfused compared with healthy controls and to evaluate the relationships of the levels of FTMT mRNA with malondialdehyde (MDA) and ferritin in these patients. METHODS The levels of FTMT mRNA in the reticulocytes of patients (30 regularly transfused and 30 rarely transfused) and 30 healthy individuals were assessed by quantitative reverse transcription-polymerase chain reaction. The levels of ferritin and MDA were analysed by ELISA and by a thiobarbituric acid reactive substance assay, respectively. RESULTS The levels of FTMT mRNA, ferritin and MDA in both groups of patients were significantly increased compared with those in the healthy controls. In addition, the levels of FTMT mRNA, ferritin and MDA in the regularly transfused patients were significantly higher than those in the rarely transfused patients. Furthermore, the relative expression levels of FTMT in patients correlated with those of MDA and ferritin. CONCLUSION These results suggest that the elevation of expression levels of FTMT in the reticulocytes of patients with alpha-thalassaemia may be associated with iron loading and oxidative stress.
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Investigation and management of a raised serum ferritin.
Cullis, JO, Fitzsimons, EJ, Griffiths, WJ, Tsochatzis, E, Thomas, DW, ,
British journal of haematology. 2018;(3):331-340
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Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.
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Are Current Serum and Plasma Ferritin Cut-offs for Iron Deficiency and Overload Accurate and Reflecting Iron Status? A Systematic Review.
Garcia-Casal, MN, Pasricha, SR, Martinez, RX, Lopez-Perez, L, Peña-Rosas, JP
Archives of medical research. 2018;(6):405-417
Abstract
BACKGROUND Serum or plasma ferritin concentration is recommended by WHO as a biomarker to assess iron status in individuals and populations. METHODS A systematic review was undertaken to summarise the evidence for ferritin reflecting iron status and to assess the cut-off points in different populations. Electronic databases were searched for studies evaluating ferritin concentrations compared against bone marrow aspirates for iron deficiency and to liver biopsies for risk of iron overload. RESULTS From 18822 records, 298 studies were assessed in full-text, including 72 studies on iron deficiency and 36 on iron overload in the quantitative analysis. All studies were observational. For iron deficiency, the mean ferritin concentration in healthy individuals was 15.1 μg/L (9 studies, 390 participants) when bone marrow iron content was 0, and 70.4 μg/L (3 studies, 151 participants) when bone marrow iron was 1+ or higher. In non-healthy populations, mean ferritin concentrations were 82.43 μg/L for iron depletion (38 studies, 1023 participants) and 381.61 μg/L for iron sufficiency (38 studies, 1549 participants) with wide variations depending on the pathology. For iron overload the results point out to a cut-off close to 500 μg/L although the data was very limited. CONCLUSION Ferritin concentration is low in iron deficient individuals and high in iron-loaded individuals, regardless of confounding clinical conditions. Current WHO thresholds for healthy populations appear valid but the data is limited for different age groups or physiological conditions. For iron overload, ferritin concentration would only help in the presumptive diagnosis and guide the need for further assessment.
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Ferritin, metabolic syndrome and its components: A systematic review and meta-analysis.
Suárez-Ortegón, MF, Ensaldo-Carrasco, E, Shi, T, McLachlan, S, Fernández-Real, JM, Wild, SH
Atherosclerosis. 2018;:97-106
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BACKGROUND AND AIMS Mechanisms for the association between iron stores and risk factors for diabetes and cardiovascular disease, such as metabolic syndrome (MetS) and its components, are still not clear. We evaluated the associations between ferritin levels, MetS and its individual components, and potential role of confounding, in a meta-analysis. METHODS We searched articles in MEDLINE and EMBASE until February 14th, 2018. There were two approaches: meta-analysis of 1) cross-sectional and longitudinal studies and 2) only cross-sectional studies. Meta-regressions were conducted to identify sources of heterogeneity in the associations of ferritin with MetS and its individual components. RESULTS Information from 26 studies (5 prospective) was systematically reviewed and 21 studies were meta-analysed. The pooled OR for MetS by increased ferritin was 1.78 (95%CI: 1.60-1.97) in the meta-analysis 1, and 1.70 (95%CI: 1.49-1.95) in the meta-analysis 2. The pooled association was weaker in studies adjusted for hepatic injury markers (meta-regression coefficient (95% CI): -0.34 (-0.60,-0.09) p = 0.008) and body mass index (BMI) (meta-regression coefficient (95% CI): -0.27 (-0.53,-0.01) p = 0.039). Among MetS components, the pooled association with increased ferritin was strongest with high triglycerides [OR (95%CI): 1.96 (1.65-2.32)] and high glucose levels [OR 95%CI: 1.60 (1.40-1.82)]. Higher cut-off points used to define high ferritin concentrations were more strongly associated with high triglycerides [meta-regression coefficient (95% CI): 0.22 (0.03, 0.041), p = 0.023]. CONCLUSIONS High triglycerides and glucose are the components more strongly associated with ferritin. Hepatic injury and BMI appear to influence the ferritin-MetS association, and a threshold effect of high ferritin concentration on the ferritin-high triglycerides association was observed.
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Noncholesterol Sterols as Surrogate Markers in Patients with Severe Alcoholic Hepatitis.
Sahlman, P, Nissinen, M, Simonen, P, Färkkilä, M
Lipids. 2018;(3):323-334
Abstract
Severe alcoholic hepatitis (AH) is a life-threatening condition lacking good serologic markers to tailor treatment and predict recovery. We examined the cholesterol metabolism in severe AH to explore prognostic markers and evaluate the profile of cholesterol precursors, cholestanol and phytosterols, in this context. We assessed serum cholesterol, cholesterol precursors, cholestanol, phytosterols, and biochemical markers in 24 patients with severe AH treated with prednisolone and randomized to ciprofloxacin in the ratio 1:1. Response to prednisolone was assessed with the Lille model. Evaluations were made between responders and nonresponders to corticosteroid treatment and during follow-up for 180 days. The findings were compared with those from patients with primary sclerosing cholangitis (PSC) (n = 156) and healthy individuals (n = 124). Responders to prednisolone had ~56-60% higher (p-value 0.032-0.044) serum ratios to cholesterol of phytosterols, while the lathosterol/campesterol ratio was ~76% (p = 0.031) lower compared to nonresponders. Stigmasterol/cholesterol predicted response to corticosteroid therapy. Surrogate markers of cholesterol synthesis (lathosterol and desmosterol) inversely reflected those of absorption (cholestanol and phytosterols) in PSC and controls (r-range -0.247 to -0.559, p < 0.01 for all), contrary to AH patients, among whom this reciprocal regulation was partially recovered on day 90 (lathosterol: r-range -0.733 to -0.952, p < 0.05 for all). AH patients had ~26% lower lathosterol/cholesterol, but 1.13-3.87-fold higher cholestanol/cholesterol and sitosterol/cholesterol compared to control groups (p < 0.05 for all). Median ferritin concentration at baseline was ~37% lower (p = 0.011) among the responders. Cholesterol precursors and phytosterols have a disease-specific profile in AH. Phytosterols and ferritin may serve as surrogate markers for short-term response.
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Differences in brain-derived neurotrophic factor between neonates born to mothers with normal and low ferritin.
Yusrawati, , Rina, G, Indrawati, LN, Machmud, R
Asia Pacific journal of clinical nutrition. 2018;(2):389-392
Abstract
BACKGROUND AND OBJECTIVES Maternal iron deficiency in late pregnancy, labor, and the postpartum period has an indirect impact to decrease neurotrophin concentration in the fetal hippocampus, namely brain-derived neurotrophic factor (BDNF). It plays an important role in the development of learning, memory, and behavior. The aim of this study was to determine the differences in BDNF between neonates born to mothers with normal and low ferritin. METHODS AND STUDY DESIGN This was an observational study with a cross-sectional design involving 20 term pregnant women with normal ferritin (>=12 ng/mL) and 20 term pregnant women with low ferritin (<12 ng/mL). Samples were taken from Yarsi hospital, BMC hospital, and Hardi clinic located in Padang, from August 2015 to February 2016. Umbilical cord plasma was examined directly after delivery using an enzymelinked immunosorbent assay (ELISA) employed at the Biomedical Laboratory of Andalas University. Mean differences were statistically assessed by independent samples t-test. RESULTS Plasma BDNF concentrations in neonates born to mothers with normal and low ferritin were 3.81±1.37 ng/mL and 2.78±1.19 ng/mL, respectively (p=0.015). CONCLUSIONS Plasma BDNF was lower in neonates born to mothers with low serum ferritin.
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Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial.
Mercer, JS, Erickson-Owens, DA, Deoni, SCL, Dean, DC, Collins, J, Parker, AB, Wang, M, Joelson, S, Mercer, EN, Padbury, JF
The Journal of pediatrics. 2018;:266-272.e2
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OBJECTIVE To evaluate whether placental transfusion influences brain myelination at 4 months of age. STUDY DESIGN A partially blinded, randomized controlled trial was conducted at a level III maternity hospital in the US. Seventy-three healthy term pregnant women and their singleton fetuses were randomized to either delayed umbilical cord clamping (DCC, >5 minutes) or immediate clamping (ICC, <20 seconds). At 4 months of age, blood was drawn for ferritin levels. Neurodevelopmental testing (Mullen Scales of Early Learning) was administered, and brain myelin content was measured with magnetic resonance imaging. Correlations between myelin content and ferritin levels and group-wise DCC vs ICC brain myelin content were completed. RESULTS In the DCC and ICC groups, clamping time was 172 ± 188 seconds vs 28 ± 76 seconds (P < .002), respectively; the 48-hour hematocrit was 57.6% vs 53.1% (P < .01). At 4 months, infants with DCC had significantly greater ferritin levels (96.4 vs 65.3 ng/dL, P = .03). There was a positive relationship between ferritin and myelin content. Infants randomized to the DCC group had greater myelin content in the internal capsule and other early maturing brain regions associated with motor, visual, and sensory processing/function. No differences were seen between groups in the Mullen testing. CONCLUSION At 4 months, infants born at term receiving DCC had greater ferritin levels and increased brain myelin in areas important for early life functional development. Endowment of iron-rich red blood cells obtained through DCC may offer a longitudinal advantage for early white matter development. TRIAL REGISTRATION ClinicalTrials.gov: NCT01620008.
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Effects of iron supplementation and nutrition education on haemoglobin, ferritin and oxidative stress in iron-deficient female adolescents in Palestine: randomized control trial.
Jalambo, M, Karim, N, Naser, I, Sharif, R
Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit. 2018;(6):560-568
Abstract
BACKGROUND Iron deficiency and iron-deficiency anaemia are associated with oxidative stress, but their role is largely unclear. Information is scarce on the effects of iron supplementation on biomarkers of oxidative stress in humans. AIMS This study evaluated the effectiveness of iron supplementation and nutrition education on improving the levels of haemoglobin and ferritin, and decreasing oxidative stress among iron-deficient female adolescents in Gaza, Palestine. METHODS A total 131 iron-deficient female adolescents were recruited and allocated randomly into 3 different groups. The iron supplementation group (A) received 200 mg of ferrous fumarate weekly during the 3-month intervention, the iron supplementation with nutrition education group (B) received iron supplements with nutrition education sessions, and the control group (C) did not receive any intervention. The levels of haemoglobin, ferritin and malonyl dialdehyde were measured at baseline, after 3 months (at which point the intervention was stopped), and then 3 months later. Trial registration number: ACTRN12618000960257. RESULTS Haemoglobin levels increased significantly after supplementation in both groups A and B. At the follow-up stage (3 months after stopping the intervention), iron and haemoglobin levels in group B continued to increase and malonyl dialdehyde decreased. In Group A, haemoglobin, ferritin and malonyl dialdehyde levels decreased after 3 months of stopping the intervention. No changes were seen in Group C. CONCLUSIONS A nutrition programme should be adopted and integrated into comprehensive intervention programmes to target iron-deficiency anaemia among female adolescents in Palestine.
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Iron: a Strong Element in the Pathogenesis of Chronic Hyperglycaemia After Acute Pancreatitis.
Chand, SK, Singh, RG, Pendharkar, SA, Petrov, MS
Biological trace element research. 2018;(1):71-79
Abstract
Evidence shows an association between markers of iron metabolism and glucose metabolism in type 2 diabetes mellitus. Acute pancreatitis is the largest contributor to diabetes of the exocrine pancreas. However, the pathogenesis of new-onset pre-diabetes or diabetes after pancreatitis remains unclear. This study aimed to investigate associations between markers of iron metabolism and glucose metabolism following acute pancreatitis. Fasting blood samples were collected to analyse markers of glucose metabolism (haemoglobin A1c) and iron metabolism (hepcidin, ferritin, and soluble transferrin receptor). Participants were categorised into two groups: normoglycaemia after acute pancreatitis and chronic hyperglycaemia after acute pancreatitis. Binary logistic and linear regression analyses were conducted, and potential confounders were adjusted for in multivariable analyses. A total of 83 individuals following an episode of acute pancreatitis were included, of whom 19 developed chronic hyperglycaemia. Hepcidin was significantly increased in individuals with chronic hyperglycaemia after acute pancreatitis in two adjusted models (p = 0.045 and p = 0.048). Ferritin was significantly decreased in individuals with chronic hyperglycaemia after acute pancreatitis in three adjusted models (p = 0.016, p = 0.009, and p = 0.011). Soluble transferrin receptor was not significantly associated with chronic hyperglycaemia after acute pancreatitis. These findings suggest that iron metabolism is significantly altered in individuals with chronic hyperglycaemia after acute pancreatitis and may provide better insights into the pathogenesis of new-onset diabetes after pancreatitis.
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Early versus delayed cord clamping in small for gestational age infants and iron stores at 3 months of age - a randomized controlled trial.
Chopra, A, Thakur, A, Garg, P, Kler, N, Gujral, K
BMC pediatrics. 2018;(1):234
Abstract
BACKGROUND Delayed cord clamping is the standard of care in infants not requiring resuscitation; however effects of cord clamping strategies have not been evaluated systematically in small for gestational age (SGA) infants. The primary objective was to compare effects of delayed cord clamping (DCC) and early cord clamping (ECC) on serum ferritin at 3 months in SGA infants born at ≥35 weeks. The secondary objectives were to compare hematological parameters, clinical outcomes in neonatal period and growth at 3 months of age. METHODS All eligible infants with fetal growth restriction were randomized to two groups, DCC at 60 s or ECC group in which the cord was clamped immediately after birth. RESULTS Total of 142 infants underwent randomization and subsequently 113 infants underwent definite inclusion. At 3 months, the median (IQR) serum ferritin levels were higher in DCC group, compared to ECC; 86 ng/ml (43.35-134.75) vs 50.5 ng/ml (29.5-83.5), p = 0.01. Fewer infants had iron deficiency in DCC group compared to ECC group; 9 (23.6%) vs 21 (47.7%), p = 0.03 [NNT being 4; 95% CI (2-25)].The proportion of infants with polycythemia was significantly higher in DCC group; 23 (41.81) % vs 12 (20.6%), p = 0.01. There was no difference in proportion of infants with symptomatic polycythemia or those who underwent partial exchange transfusions. Clinical outcomes and mortality were similar. CONCLUSIONS DCC improves iron stores in SGA infants ≥35 weeks at 3 months of age without increasing the risk of symptomatic polycythemia, need for partial exchange transfusions or morbidities associated with polycythemia. TRIAL REGISTRATION Our trial was retrospectively registered on 29th May 2015 through Clinical trials registry India. Registration number: CTRI 2015/05/005828 .