Plasma Ferritin Research Articles

Iron storage disease (hemochromatosis) and hepcidin response to iron load in two species of pteropodid fruit bats relative to the common vampire bat.

Hepcidin is the key regulator of iron homeostasis in the body. Iron storage disease (hemochromatosis) is a frequent cause of liver disease and mortality in captive Egyptian fruit bats (Rousettus aegyptiacus), but reasons underlying this condition are unknown. Hereditary hemochromatosis in humans is due to deficiency of hepcidin or resistance to the action of hepcidin. Here, we investigated the role of hepcidin in iron metabolism in one species of pteropodid bat that is prone to iron storage disease [Egyptian fruit bat (with and without hemochromatosis)], one species of pteropodid bat where iron storage disease is rare [straw-colored fruit bat (Eidolon helvum)], and one species of bat with a natural diet very high in iron, in which iron storage disease is not reported [common vampire bat (Desmodus rotundus)]. Iron challenge via intramuscular injection of iron dextran resulted in significantly increased liver iron content and histologic iron scores in all three species, and increased plasma iron in Egyptian fruit bats and straw-colored fruit bats. Hepcidin mRNA expression increased in response to iron administration in healthy Egyptian fruit bats and common vampire bats, but not in straw-colored fruit bats or Egyptian fruit bats with hemochromatosis. Hepcidin gene expression significantly correlated with liver iron content in Egyptian fruit bats and common vampire bats, and with transferrin saturation and plasma ferritin concentration in Egyptian fruit bats. Induction of hepcidin gene expression in response to iron challenge is absent in straw-colored fruit bats and in Egyptian fruit bats with hemochromatosis and, relative to common vampire bats and healthy humans, is low in Egyptain fruit bats without hemochromatosis. Limited hepcidin response to iron challenge may contribute to the increased susceptibility of Egyptian fruit bats to iron storage disease.

The preventive effect of<em> Mangifera foetida</em> L. leaf extract administered simultaneously to excess iron on markers of iron overload in Spraque-Dawley rats

Background: Recently, there is no agent available for the prevention of iron overload (IO) in thalassemia patients. Previous studies showed that Mangifera foetida L. leaf extracts reduced the levels of iron in IO in vitro and in vivo models. The present study aimed to determine the efficacy of Mangifera foetida L. leaf extract in the prevention of IO induced in rats.Methods: Thirty male Sprague-Dawley rats were divided into 5 groups: control (untreated), IO, 3 treatment groups with leaf extract equivalent to 50, 100, and 200 mg of mangiferin per kg BW. Fe-dextran (15 mg) was administered intraperitoneally twice a week for 4 weeks to all groups except control (IO, DSM50, DSM100, and DSM200). Urine and blood samples were taken before and after treatments. After 4 weeks of treatment, rats were terminated, and samples of spleen, liver, and heart were taken. Ferritin and mangiferin levels and SOD activities were determined in plasma. Iron levels were measured in plasma, urine, and spleen.Results: Experimental IO increased plasma Fe content 4.23 times and plasma ferritin levels 6.9 times vs normal. Mangifera foetida L. leaf extract DSM50 resulted in the highest blood levels of 212 ng mangiferin per mL and moderately, although not significant, prevented increased plasma ferritin levels and IO in organs and protected against oxidative stress.Conclusion: Aqueous Mangifera foetida L. leaf extract may be useful to prevent IO and oxidative stress in thalassemia patients.

Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study.

It is unknown why increased plasma ferritin concentration predicts all-cause mortality. As low-grade inflammation and increased plasma ferritin concentration are associated with all-cause mortality, we hypothesized that increased plasma ferritin concentration is genetically associated with low-grade inflammation. We investigated whether increased plasma ferritin concentration is associated with low-grade inflammation [i.e., increased concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in 62537 individuals from the Danish general population. We also applied a Mendelian randomization approach, using the hemochromatosis genotype C282Y/C282Y as an instrument for increased plasma ferritin concentration, to assess causality. For a doubling in plasma ferritin concentration, the odds ratio (95% CI) for CRP ≥2 vs <2 mg/L was 1.12 (1.09-1.16), with a corresponding genetic estimate for C282Y/C282Y of 1.03 (1.01-1.06). For a doubling in plasma ferritin concentration, odds ratio (95% CI) for complement C3 >1.04 vs ≤1.04 g/L was 1.28 (1.21-1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06 (1.03-1.12). Mediation analyses showed that 74% (95% CI, 24-123) of the association of C282Y/C282Y with risk of increased CRP and 56% (17%-96%) of the association of C282Y/C282Y with risk of increased complement C3 were mediated through plasma ferritin concentration. Increased plasma ferritin concentration as a marker of increased iron concentration is associated observationally and genetically with low-grade inflammation, possibly indicating a causal relationship from increased ferritin to inflammation. However, as HFE may also play an immunological role indicating pleiotropy and as incomplete penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the study design could bias the genetic estimates.

Iron status among under-five children with first febrile convulsion and subsequent febrile convulsion

Objective: The objective of this study is to estimate the iron status using hemoglobin (Hb), red cell indices, serum iron, plasma ferritin, total iron binding capacity (TIBC), and transferrin saturation (TSAT) in children with first febrile convulsion (FFC) and subsequent FC (SFC). Methods: The study was conducted in a tertiary care teaching hospital among children aged 6 months–5 years with first and subsequent episodes of the simple FC taking cases and controls in a ratio of 2:2:1. Consecutive cases and concurrent controls were selected for the study. Controls were children of the same age group with short febrile illness but without any seizures. After informed consent from parents, detailed history was taken; clinical examination and blood investigations were done to estimate iron status in both cases and controls. Laboratory tests included Hb, hematocrit( Hct), red cell indices, peripheral smear, red cell distribution width (RDW), serum iron concentration, plasma ferritin, TIBC, and TSAT. The data were then analyzed statistically using SPSS software. Results: 44 cases with FFC, 44 with SFC, and 22 controls were included in the study. The mean Hb, Hct, red cell indices, and RDW between the three groups did not show any significant difference. The mean serum ferritin was significantly lower in the SFC group compared to the control group (p=0.005). The mean serum TIBC was significantly higher in the SFC group compared to the control group (p=0.004) and also the SFC group compared to the FFC group (p=0.022). Conclusions: Poor iron status in subsequent febrile seizures indicates that iron deficiency is associated with subsequent seizures. Hence, screening for iron status rather than Hb level estimation should be considered for children presenting with or at high risk for febrile seizures.

Deficiencia de vitamina D y de hierro en niños y adolescentes con parálisis cerebral

IntroductionChildren and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. ObjectiveTo describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. Patients and methodWe performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. ResultsPatients’ mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). ConclusionsThe patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies.

The Correlation of Cardiac and Hepatic Hemosiderosis as Measured by T2*MRI Technique with Ferritin Levels and Hemochromatosis Gene Mutations in Iranian Patients with Beta Thalassemia Major.

Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major (BTM) compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels. We studied 60 patients with BTM with a mean age of 17.5±9.1 years from the Northwest of Iran. HFE gene mutations were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. Cardiac and hepatic hemosiderosis was assessed using T2*magnetic resonance imaging (MRI). Ferritin levels were measured using the enzyme immunoassay method. Ferritin levels showed a strong inverse correlation with hepatic T2*MRI values (r = -0.631, p = 0.001) but a poor correlation with cardiac T2*MRI values (r = -0.297, p = 0.044). The correlation between cardiac T2*MRI values and hepatic T2*MRI values was poor and insignificant (r = 0.287, p = 0.058). Genotype and allele distribution of HFE H63D and C282Y mutation did not differ significantly between patients with and without hepatic or cardiac hemosiderosis (p > 0.050). However, carriers of HFE 63D allele had significantly higher ferritin levels compared with non-carriers (1 903±993 vs. 992±683, p < 0.001). Cardiac T2*MRI values showed a poor correlation with hepatic T2*MRI values and ferritin levels. Accurate assessment of cardiac iron overload in patients with BTM can only be done using the T2*MRI technique. Additionally, HFE H63D is a significant determinant factor for elevated ferritin levels in BTM patients.

A sandwich enzyme-linked immunosorbent assay for the quantitation of human plasma ferritin

There is a lack of published enzyme linked immunosorbent assay (ELISA) protocols which use commercially available reagents for the measurement of ferritin in human plasma for research purposes. ELISA kits are often expensive and do not always provide detailed information about reagents included. A commercially available antibody pair was used to develop an in-house ELISA to measure ferritin in small (25?µl) volumes of human plasma. ELISA results were compared to ferritin levels measured using a commercial immune-assay system. The sensitivity, intra and inter assay variation of the ELISA assay were also determined. ELISA measurements of plasma ferritin ranged between 3.2–232?ng/mL and were comparable to those measured by a commercial immunoassay system (Pearson correlation r?=?0.93 P?<?0.0001). Ferritin levels as low as 0.5?ng/mL were detectable and samples with both low and normal ferritin levels showed low inter and intra-assay variation. This ELISA protocol allows the accurate, reliable and cost-effective quantitative determination of plasma ferritin levels from small volumes of human plasma.•No published protocols detail how to measure ferritin by ELISA using commercially available antibodies.•ELISA kits are expensive and information on antibodies included are often lacking.•We have identified a commercially available antibody pair to measure plasma ferritin using a cost-effective ELISA.

Plasma Ferritin Levels, Oxidative Stress and Nephropathy in Diabetes

Background: Elevated plasma levels of ferritin and oxidative stress have been associated with diabetic nephropathy; the onset of which is insidious. The early stages of glomerular hyper filtration often go unnoticed in the majority of subjects. This limit the precision of creatinine based glomerular filtration rate estimates. Objective: We sought to document the role of plasma ferritin and oxidative stress markers in the early detection of nephropathy in diabetes mellitus (DM). Subjects and Methods: This was a cross sectional analytical study conducted on 360 participants, comprising of 220 with DM and 140 age matched apparently healthy control individuals. Fasting blood samples were collected for the estimations of glucose, plasma ferritin, urea, creatinine and oxidative stress markers (malondialdehyde, superoxide dismutase, reduced glutathione and catalase). Results: The mean ferritin levels in DM (83.77 ± 4.18 ng/ml) was significantly higher than the controls (55.60 ± 10.41ng/ml) (p = 0.004) . A significant correlation of ferritin and malondiadehyde (r = 0.422, p = 0.050) was observed in DM. Inverse associations of creatinine and superoxide dismutase (r = -0.298, p = 0.011), as well creatinine and catalase (r = -0.270, p = 0.022) were observed in DM. Possible predictors of nephropathy include ferritin, superoxide dismutase, catalase and reduced glutathione. Conclusion: Elevated plasma ferritin levels in addition to some antioxidant enzymes, notably superoxide dismutase and catalase, contribute to the pathogenesis of nephropathy in DM.

Red meat consumption and risk of cardiovascular diseases—is increased iron load a possible link?

High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load. The object of the study was to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study. We evaluated relations between red meat consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC-Heidelberg Study using a case-cohort sample including a random subcohort (n = 2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n = 513), and CVD mortality (n = 381). Following a 4-step mediation analysis, associations between red meat consumption and iron load, red meat consumption and CVD risk, and iron load and CVD risk were assessed by multivariable regression models before finally testing to which degree associations between red meat consumption and CVD risk were attenuated by adjustment for iron status. Red meat consumption was significantly positively associated with ferritin concentrations and MI risk [HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33)], but no significant associations with stroke risk and CVD mortality were observed. While direct associations between ferritin concentrations and MI risk as well as CVD mortality were significant in age- and sex-adjusted Cox regression models, these associations were substantially attenuated and no longer significant after multivariable adjustment for classical CVD risk factors. Strikingly, ferritin concentrations were positively associated with a majority of classical CVD risk factors (age, male sex, alcohol intake, obesity, inflammation, and lower education). Increased ferritin concentrations may be a marker of an overall unfavorable risk factor profile rather than a mediator of greater CVD risk due to meat consumption.

Iron metabolism parameters in patients with chronic heart failure and reduced left ventricular ejection fraction depending on basic demographic, clinical and instrumental characteristics

The aim – to study the iron metabolism parameters in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (rLVEF) depending on main clinical characteristics of patients obtained during the instrumental study. Material and methods. During period from January 2016 till February 2018, 134 stable patients with CHF (113 (84.3 %) of men and 21 (15.7 %) of women), 18–75 years old, NYHA class II–IV, with left ventricular ejection fraction &lt; 40 % were screened. Patients were included at a clinical compensation phase. Quality of life was assessed by the Minnesota living with heart failure questionnaire (MLHFQ), physical activity was estimated by the Duke University index, functional status – by assessing the 6-minute walking test (6MWT) and a standardized lower limb extension test.Results and discussion. Iron deficiency was found in 83 (62 %) of 134 patients with CHF and rLVEF. There were no significant differences of iron metabolism in regard to CHF etiology and most co-morbidities. The presence of anemia was associated with lower ferritin, transferrin saturation (TSAT) and serum iron levels, and the presence of renal dysfunction – with the latter two. Patients in NYHA III–IV class had significantly lower TSAT and serum iron levels. The ferritin level was significantly higher only in group of patients with better muscular endurance, while TSAT and serum iron levels were also significantly higher in patients with greater 6-minutes walking distance, better hip muscles endurance, greater physical activity index and fewer scores by the Minnesota quality of life scale. Ferritin has shown a significant correlation with serum iron levels and hemoglobin. TSAT level correlated with a serum iron level, hemoglobin, limb muscles endurance, 6-minute walking test result, physical activity index and MLHFQ score.Conclusions. Iron deficiency has been revealed in 62 % of patients with CHF and rLVEF. The plasma ferritin level is lower in patients with anemia and with worse muscle endurance. TSAT and serum iron levels are lower in patients with NYHA III–IV class, anemia, renal dysfunction, worse physical tolerance indicators and poorer quality of life. Both ferritin and TSAT demonstrate a relation to hemoglobin and iron plasma level, additionally TSAT – with physical activity index, 6-minutes walking test distance (6MWT), quadriceps femoris muscle endurance and MLHFQ quality of life.

Micronutrient status in middle childhood and age at menarche: results from the Bogotá School Children Cohort.

Childhood intake of animal foods is associated with age at first menstrual period (menarche). It is unknown whether the micronutrients present in these foods could explain this association. Our objective was to investigate the associations of micronutrient status biomarkers in middle childhood with age at menarche. We quantified circulating Hb, ferritin, mean corpuscular volume, Zn, vitamin B12, erythrocyte folate and retinol in 1464 pre-menarcheal girls aged 5-12 years in Bogotá, Colombia, and followed them for a median 5·7 years for the occurrence and date of menarche. We estimated median age at menarche and hazard ratios (HR) with 95 % CI by levels of each biomarker with use of Kaplan-Meier survival probabilities and Cox regression, respectively. Median age at menarche was 12·4 years. Middle childhood Hb was inversely related to age at menarche whereas plasma ferritin was positively associated with this outcome in a linear manner. HR of menarche for every 1 sd of Hb (11 g/l) and ferritin (23·2 µg/l) were 1·11 (95 % CI 1·04, 1·18; P=0·001) and 0·94 (95 % CI 0·88, 0·99; P=0·02), respectively, after adjustment for baseline age, C-reactive protein concentration, maternal age at menarche and parity and socioeconomic status. The association with ferritin was stronger in girls aged 9-10 years at baseline. Additional adjustment for baseline height- and BMI-for-age did not change the results. We conclude that higher Fe status in middle childhood is related to later age at menarche whereas Hb concentrations are inversely associated with age at onset of menses.

Assessment of iron status in settings of inflammation: challenges and potential approaches

The determination of iron status is challenging when concomitant infection and inflammation are present because of confounding effects of the acute-phase response on the interpretation of most iron indicators. This review summarizes the effects of inflammation on indicators of iron status and assesses the impact of a regression analysis to adjust for inflammation on estimates of iron deficiency (ID) in low– and high–infection-burden settings. We overviewed cross-sectional data from 16 surveys for preschool children (PSC) (n = 29,765) and from 10 surveys for nonpregnant women of reproductive age (WRA) (n = 25,731) from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Effects of C-reactive protein (CRP) and α1-acid glycoprotein (AGP) concentrations on estimates of ID according to serum ferritin (SF) (used generically to include plasma ferritin), soluble transferrin receptor (sTfR), and total body iron (TBI) were summarized in relation to infection burden (in the United States compared with other countries) and population group (PSC compared with WRA). Effects of the concentrations of CRP and AGP on SF, sTfR, and TBI were generally linear, especially in PSC. Overall, regression correction changed the estimated prevalence of ID in PSC by a median of +25 percentage points (pps) when SF concentrations were used, by −15 pps when sTfR concentrations were used, and by +14 pps when TBI was used; the estimated prevalence of ID in WRA changed by a median of +8 pps when SF concentrations were used, by −10 pps when sTfR concentrations were used, and by +3 pps when TBI was used. In the United States, inflammation correction was done only for CRP concentrations because AGP concentrations were not measured; regression correction for CRP concentrations increased the estimated prevalence of ID when SF concentrations were used by 3 pps in PSC and by 7 pps in WRA. The correction of iron-status indicators for inflammation with the use of regression correction appears to substantially change estimates of ID prevalence in low– and high–infection-burden countries. More research is needed to determine the validity of inflammation-corrected estimates, their dependence on the etiology of inflammation, and their applicability to individual iron-status assessment in clinical settings.

Diagnostic Value of NT-pro BNP Biomarker and Echocardiography in Cardiac Involvements in Beta-thalassemia Patients

Background N-terminal pro–B-type natriuretic peptide (NT-proBNP) is a marker to evaluate the cardiac involvement in thalassemia. We aimed to evaluate conventional and tissue Doppler echocardiography findings and its relation to plasma NT-pro BNP, Ferritin and Iron levels in beta-thalassemia patients. Materials and Methods This study performed on 164 participants equal of major beta- thalassemia patients (n=82), and controls (82 healthy children with normal cardiovascular status). The patients collected from outpatients after applied exclusion criteria. Blood samples were taken from participants in fasting to measure NT- pro BNP, Ferritin and Iron serum. Participants were under echocardiography by Pediatric cardiologist. The level of error considered as 0.05 for data analysis by SPSS version 20.0. Results NT- pro BNP, Iron, Ferritin, left S', left A', right A', EF, FS, left and right A/A'; right and left MPI were significantly different in patients group (P 10 years, and FS had different values significantly in lower levels. In lower level of left E/E' resulted that FS was significantly higher in the age group < 10 years. Right peak E velocity was significantly higher in younger’s in higher level of left E/E'. Right E/E' was significantly higher in elders in lower level of left E/E' (P<0.05). Conclusion The study confirmed that NT-pro BNP increases in thalassemia and association with age and LV diastolic dysfunction. NT-pro BNP with E/E' and S' were shown diastolic and systolic dysfunction in thalassemia. Therefore, an increased level of ferritin and NT-pro BNP can be used as a marker for the intensification of iron chelation therapy, which reverses iron-induced cardiomyopathy.

EFFECTS OF EMODIN ON BLOOD GLUCOSE AND BODY WEIGHT IN TYPE 1 DIABETIC RATS

Objectives: Objective of present study was to analyze the effect of emodin on blood glucose and body weight in rats with type 1 diabetes. Methods: A total of 45 healthy SD rats were selected followed by being adaptively fed for one week and then from them 15 rats were randomly selected out as the control group and the remaining 30 healthy SD rats were given intra peritoneal injection of streptozotocin to establish diabetic model with the control group receiving intra peritoneal injection of citrate buffer solution of same doses; At the fifth day, the rats were fasted for 6h and appropriately fed with water. Then the tail blood was collected to measure the fasting blood glucose of rats and this step was repeated 15 days after the injection of streptozotocin. Results: The diabetic rat model was established successfully when the blood glucose was detected to be no less than 16.9mmol/l; thirty diabetic model rats were randomly divided into diabetes group and emodin group with 15 cases in each group (n=15); 15 days later, the rats in diabetes group and control group were treated with intra gastric administration of PBS, 5ml/kg, and the rats in emodin group were given intra gastric administration of emodin suspension (8g/l), 5ml/kg. The changes of fasting blood glucose and body weight were observed and compared in three groups from the time point of before model establishment to fifth and fifteenth days after successful establishment of model. Conclusion: There was no significant difference among three groups in fasting blood glucose and body weight at the initial stage of establishing model; In diabetes group and emodin group, the rat’s body weight in T2 was significantly lower than that in T1 with the body weight decreasing more significantly in diabetes group (P<0.05), while the blood glucose in T2 was significantly higher than that in T1 with the blood glucose increasing more significantly in diabetes group (P<0.05). Emodin can relieve hyperglycemia in type 1 diabetic rats but has little influence on body weight. Peer Review History: Received 6 August 2017; Revised 8 September; Accepted 11 September, Available online 15 September 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.5/10 Reviewer(s) detail: Dr. Sabah Hussien El-Ghaiesh, Tanta University, Egypt, s.ghaiesh@gmail.com Dr. Ali Abdullah A. Al-Mehdar, University of Basrah, Iraq, asia_abdullah65@yahoo.com Similar Articles: PLASMA FERRITIN AND HEPCIDIN LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Relationship between iron deficiency anemia and febrile seizures in children: A systematic review and meta-analysis

PurposeThe association between iron deficiency anemia (IDA) and febrile seizures (FS) during childhood is inconclusive due to inconsistent results reported in different studies. We performed a systematic review and meta-analysis to determine an association between IDA and FS in children. MethodsWe searched PubMed, EMBASE, and Cochrane Library databases for studies published up to August 2015 using the following key words: [“iron deficiency” OR “iron status”] AND [“febrile seizure” OR “febrile convulsion”] AND [“pediatric” OR “infant” OR “child”]. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using standard meta-analysis techniques. Subgroup analysis also was performed. ResultsA total of 17 studies enrolling 2416 children with FS and 2387 controls were included in the meta-analysis. The results indicated that IDA was significantly associated with FS (OR, 1.98; 95% CI, 1.26–3.13; P=0.003). Subgroup analyses evaluated the diagnostic indices for IDA including serum iron, plasma ferritin, and mean corpuscular volume (MCV). The results indicated that IDA diagnosed on the basis of plasma ferritin (OR, 3.78; 95% CI, 1.80–7.94; P<0.001) or MCV (OR, 2.08; 95% CI, 1.36–3.17; P=0.001) was modestly associated with FS, whereas IDA diagnosed on the basis of two serum iron studies was not associated with FS (OR, 0.57; 95% CI, 0.24–1.37; P=0.210). ConclusionThe results of this meta-analysis suggest that IDA is associated with an increased risk of FS in children.

Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study.

BackgroundAnemia, which has many etiologies, is a moderate/severe public health problem in young children and women of reproductive age in many developing countries. The aim of this study was to investigate prevalence of iron deficiency, anemia, and iron deficiency anemia using multiple biomarkers and to evaluate their association with food insecurity and food consumption patterns in non-pregnant women from a rural area of southern Ethiopia.MethodsA cross-sectional study was conducted in 202 rural women of reproductive age in southern Ethiopia. Anthropometrics and socio-demographic data were collected. A venipuncture blood sample was analyzed for hemoglobin (Hb) and for biomarkers of iron status. Biomarkers were skewed and were log transformed before analysis. Mean, median, Pearson’s correlations and ordinary least-squares regressions were calculated.ResultsMedian (IQR) Hb was 138 (127, 151) g/L. Based on an altitude-adjusted (1708 m) cutoff of 125 g/L for Hb, 21.3% were anemic. Plasma ferritin was <15 μg/L in 18.6% of the women. Only one woman had α-1-acid glycoprotein (AGP) >1.0 g/L; four women (2%) had > 5 mg/L of C-reactive protein (CRP). Of the 43 women who were anemic, 23.3% (10 women) had depleted iron stores based on plasma ferritin. Three of these had elevated soluble transferrin receptors (sTfR). Hemoglobin (Hb) concentration was negatively correlated with sTfR (r = -0.24, p = 0.001), and positively correlated with ferritin (r = 0.17, p = 0.018), plasma iron (r = 0.15, p = 0.046), transferrin saturation (TfS) (r = 0.15, p = 0.04) and body iron (r = 0.14, p = 0.05). Overall prevalence of iron deficiency anemia was only 5%.ConclusionIron deficiency anemia was not prevalent in the study population, despite the fact that anemia would be classified as a moderate public health problem.

The prevalence and factors associated with stunting among infants aged 6 months in a peri-urban South African community.

To determine the prevalence and factors associated with stunting in 6-month-old South African infants. This cross-sectional study was part of the baseline of a randomized controlled trial. Weight-for-length, length-for-age and weight-for-age Z-scores were based on the WHO classification. Blood samples were analysed for Hb, plasma ferritin and soluble transferrin receptor (sTfR). Socio-economic, breast-feeding and complementary feeding practices were assessed by questionnaire. Setting/Subjects Infants aged 6 months (n 750) from a peri-urban area of Matlosana Municipality, North West Province of South Africa. Stunting, underweight, wasting and overweight affected 28·5, 11·1, 1·7 and 10·1 % of infants, respectively. Exclusive breast-feeding to 6 months of age was reported in 5·9 % of the infants. Multivariable binary logistic regression showed that birth weight (OR=0·12; 95 % CI 0·07, 0·21, P8·3 mg/l) concentrations. The association between stunting and lower birth weight, shorter maternal height and male sex reflects possibly the intergenerational origins of stunting. Therefore, interventions that focus on improving preconceptual and maternal nutritional status, combined with strategies to promote appropriate infant feeding practices, may be an important strategy to prevent stunting in vulnerable settings.

The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease.

Hepcidin secreted by hepatocytes is a key regulator of iron metabolism throughout the body. Hepcidin concentrations are increased in chronic kidney disease (CKD), contributing to abnormalities in iron metabolism. Levels of indoxyl sulfate (IS), a uremic toxin, are also elevated in CKD. However, the effect of IS accumulation on iron metabolism remains unclear. We used HepG2 cells to determine the mechanism by which IS regulates hepcidin concentrations. We also used a mouse model of adenine-induced CKD. The CKD mice were divided into two groups: one was treated using AST-120 and the other received no treatment. We examined control mice, CKD mice, CKD mice treated using AST-120 and mice treated with IS via drinking water. In the in vitro experiments using HepG2 cells, IS increased hepcidin expression in a dose-dependent manner. Silencing of the aryl hydrocarbon receptor (AhR) inhibited IS-induced hepcidin expression. Furthermore, IS induced oxidative stress and antioxidant drugs diminished IS-induced hepcidin expression. Adenine-induced CKD mice demonstrated an increase in hepcidin concentrations; this increase was reduced by AST-120, an oral adsorbent of the uremic toxin. CKD mice showed renal anemia, decreased plasma iron concentration, increased plasma ferritin and increased iron content in the spleen. Ferroportin was decreased in the duodenum and increased in the spleen. These changes were ameliorated by AST-120 treatment. Mice treated by direct IS administration showed hepatic hepcidin upregulation. IS affects iron metabolism in CKD by participating in hepcidin regulation via pathways that depend on AhR and oxidative stress.

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan preschool children: a community-based survey

BackgroundZinc protoporphyrin (ZPP) has been used to screen and manage iron deficiency in individual children, but it has also been recommended to assess population iron status. The diagnostic utility of ZPP used in combination with haemoglobin concentration has not been evaluated in pre-school children. We aimed to a) identify factors associated with ZPP in children aged 12–36 months; b) assess the diagnostic performance and utility of ZPP, either alone or in combination with haemoglobin, to detect iron deficiency.MethodsWe used baseline data from 338 Kenyan children enrolled in a community-based randomised trial. To identify factors related to ZZP measured in whole blood or erythrocytes, we used bivariate and multiple linear regression analysis. To assess diagnostic performance, we excluded children with elevated plasma concentrations of C-reactive protein or α1-acid glycoprotein, and with Plasmodium infection, and we analysed receiver operating characteristics (ROC) curves, with iron deficiency defined as plasma ferritin concentration < 12 μg/L. We also developed models to assess the diagnostic utility of ZPP and haemoglobin concentration when used to screen for iron deficiency.ResultsWhole blood ZPP and erythrocyte ZPP were independently associated with haemoglobin concentration, Plasmodium infection and plasma concentrations of soluble transferrin receptor, ferritin, and C-reactive protein. In children without inflammation or Plasmodium infection, the prevalence of true iron deficiency was 32.1%, compared to prevalence of 97.5% and 95.1% when assessed by whole blood ZPP and erythrocyte ZPP with conventional cut-off points (70 μmol/mol and 40 μmol/mol haem, respectively). Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve (84.0%, p = 0.003, and 84.2%, p = 0.001, respectively, versus 62.7%). A diagnostic rule (0.038689 [haemoglobin concentration, g/L] + 0.00694 [whole blood ZPP, μmol/mol haem] >5.93120) correctly ruled out iron deficiency in 37.4%–53.7% of children screened, depending on the true prevalence, with both specificity and negative predictive value ≥90%.ConclusionsIn young children, whole blood ZPP and erythrocyte ZPP have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone. A single diagnostic score based on haemoglobin concentration and whole blood ZPP can rule out iron deficiency in a substantial proportion of children screened.Trial registrationClinicalTrials.gov NCT02073149 (25 February 2014).

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a 9-month cluster-randomized controlled trial conducted in south-central Côte d’Ivoire. 378 children aged 12–36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (ID; PF < 30 μg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44–66%, and 57–76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on ID with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).