Normal Iron Levels Research Articles

Iron starvation results in up-regulation of a probable Haloferax volcanii siderophore transporter.

The response of the haloarchaeal model organism Haloferax volcanii to iron starvation was analyzed at the proteome level by data-independent acquisition mass spectrometry. Cells grown in minimal medium with normal iron levels were compared to those grown under low iron conditions, with samples being separated into membrane and cytoplasmic fractions in order to focus on import/export processes which are frequently associated with metal homeostasis. Iron starvation not only caused a severe retardation of growth but also altered the levels of many proteins. Using a comprehensive annotated spectral library and data-independent acquisition mass spectrometry (DIA-MS), we found that iron starvation resulted in significant changes to both the membrane and the soluble proteomes of Hfx. volcanii. The most affected protein is the RND family permease HVO_A0467, which is 44-fold enriched in cells grown under iron starvation. The gene HVO_A0467 can be deleted suggesting that it is not essential under standard conditions. Compared to wild type cells the deletion strain shows only slight changes in growth and cell morphologies show no differences. Molecular docking predictions indicated that HVO_A0467 may be an exporter of the siderophore schizokinen for which a potential biosynthesis cluster is encoded in the Hfx. volcanii genome. Together, these findings confirm the importance of iron for archaeal cells and suggest HVO_0467 as a siderophore exporter.

Alcohol- and Low-Iron Induced Changes in Antioxidant and Energy Metabolism Associated with Protein Lys Acetylation.

Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption.

Moyamoya Syndrome in a Child with Beta-Thalassemia Trait: A Case Report with Review of Literature

Background: The association of moyamoya angiopathy with hematological conditions such as sickle cell anemia and beta-thalassemia major or intermedia is well-known, but moyamoya syndrome (MMS) associated with thalassemia trait is hardly reported. We report such a rare association. Clinical Description: A 7-year-old boy presented with right-sided monoparesis with right-sided focal seizures, along with right-sided upper motor neuron type facial nerve palsy. He had a history of recurrent transient episodes of limb weakness, which were unevaluated. Examination revealed pallor and mild splenomegaly. Management and Outcome: Routine investigations revealed microcytic hypochromic anemia with normal serum iron levels. High-performance liquid chromatography was suggestive of beta-thalassemia trait. Contrast-enhanced computerized tomography of the head showed infarction in the territory of the left anterior cerebral artery (ACA) and middle cerebral artery (MCA). Magnetic resonance angiography revealed significantly attenuated bilateral internal carotid arteries in the supraclinoid region with attenuated bilateral ACA and bilateral MCA along with collateral formation suggestive of moyamoya angiopathy. The final diagnosis of MMS secondary to beta-thalassemia trait was made. The child improved with aspirin and supportive management. Conclusion: MMS can be rarely associated with the beta-thalassemia trait. Such an underlying, unsuspected heterozygous beta-thalassemia (trait) may be diagnosed only after the identification of moyamoya disease following a stroke.

Plasma D-Dimer Value Corrected with Some Physiological and Inflammatory Markers (C-Reactive Protein and Ferritin) in Iraqi Patients with COVID-19 Infection

Since the beginning of the COVID-19 pandemic it has been observed that patients have elevated plasma levels of D-dimer and some inflammatory markers (ferritin, interleukine 6, C-reactive protein (CRP) or fibrinogen). Some studies point to the existence of a certain correlation between those markers and D-dimer. CRP is a protein discovered in the 1930s by Tillett and Francis and is an acute phase reactant. It is a pentameric protein which is synthesized by the liver under the action of cytokine interleukin 6 (IL-6). D-dimers are multiple peptide fragments produced as a result of degradation of crosslinked fibrin, mediated by plasmin. A total of 60 patients were recruited and categorized into :1- group1 (controls), 2- group 2 (COVID-19 patients). 5 ml of blood was obtained from each patient by vein puncture, using 5 ml disposable syringes, then centrifuged at 3000 rpm for 10 minutes to collect the serum. D- dimer, C-reactive protein were measured by using (Roche Diagnostics GmbH, Mannheim, Germany). At the same time, the Ferritin was assessed by using a miniVIDAS analyzer for the fluorescent enzymatic detection of β2-microglobulin (β2M) using the technique. Enzyme Linked Fluorescent Assay (ELFA) (BioMerieux). Our results showed that there was a non- significant difference in the P-values between control and patients males and females. The Mean ± SE of age in control group was 45.90 ± 3.34, while the Mean ± SE of age in patients was 45.35 ± 2.52. There was a non- significant difference between the two groups, the Mean ± SE of CRP in control group was 5.04 ±0.81, while the Mean ± SE of CRP in COVID-19 patients was 37.16 ±3.24, there was a highly Significant differences between them (P≤0.01). The CRP of COVID-19 patients were compared with those of control patients, the results shows significant increased CRP in covid-19 patients group as a compression with the control group, the findings of the study is similar to Jacob Lentner, etal findings. In response to infections, the liver synthesizes significant quantities of acute-phase proteins (APPs), such as CRP. This acute inflammatory protein is a highly sensitive biomarker for inflammation, tissue damage, and infection. It has been shown that CRP levels are correlated with levels of inflammation. CRP levels can promote phagocytosis and activate the complement system. In other words, CRP binds to microorganisms and promotes their removal through phagocytosis. D-dimers are one of the fragments produced when plasmin cleaves fibrin to break down clots. Our study showed that the serum D-dimer concentrations in patients significantly higher than those in control group which is similar to Mamta Soni, etal, 2020 findings. Elevated D-dimer levels have emerged as a consistent finding in severely ill COVID-19 patients, Multiple studies have identified an association between higher D-dimer levels and an increased risk of mortality in the COVID-19 patient population. Ferritin is an iron-storing protein; its serum level reflects the normal iron level and helps the diagnosis of iron deficiency anemia. Circulation ferritin level increases during viral infections and can be a marker of viral replication. Our study showed a significant increase in ferritin level in covid-19 patients group compared to control group, which consider similar to [] results. Although the exact cause for elevated ferritin in COVID-19 infection is unknown, it could be influenced by cytokine release or cellular damage that results in the leakage of intracellular ferritin. It has been previously shown that ferritin is a direct indicator of cellular damage suggestive of an association between organ damage and ferritin production. This could later cause cell death, known as ferroptosis. It is suggested that inflammation associated with sepsis could alter iron metabolism and deficiency to facilitate the immune system, which could be an early sign of COVID.

Effect of iron supplementation on physical and physiological variables of active females

Introduction: This study investigates the impact of iron supplementation on physiological and physical variables among active female students. Iron is essential for oxygen transport and is routinely depleted among iron runners due to exercise intensity. Considering the complicated relationship between exercise intensity, participants’ current health status, eating habits, and normal iron levels, this study seeks to illuminate whether iron supplementation benefits female athletes recruited among students from Burdwan University’s M.P.Ed. Department. Materials and Methods: This study targets a population of 10 female students aged between 22 and 27 years. Participants were selected on the basis of the homogeneity of their age, height, and weight. The study design was conducted as pretest/posttest research. Participants were provided with iron supplements, Punarnaba Moondur, with 250 mg of iron to be taken twice a day with honey and fed as specified. Hemoglobin level and various physiological and physical test parameters were chosen as primary outcomes. Using a t-test setting, P = 0.05, the difference between pre- and postparameters was analyzed. Results: Analysis indicates significant positive variations in postintervention hemoglobin level results in relation to preintervention results. Thus, the iron level was successfully increased. Comparably, various physiological functions and physical fitness parameters were improved among the participants: Their muscles worked more efficiently, and physical capabilities were generally enhanced. Conclusion: The use of Punarnaba Moondur as an iron supplement significantly increased the amount of hemoglobin among the active students. This development led to improved physiological and physical capacity. Parametric supplementation can be used to correct exercise-induced iron deficiency in female athletes to increase exercise performance and health outcomes. This study highlights the value of attenuation nutrition as an intervention tool against exercise-induced iron depletion.

Dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes: correction by gene editing and pharmacological treatment.

Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment is currently available. The purpose of the study was to identify new molecular signatures of the cardiomyopathy development in DMD. For modelling of DMD-associated cardiomyopathy, we prepared three pairs of isogenic control and dystrophin-deficient human induced pluripotent stem cell (hiPSC) lines. Two isogenic hiPSC lines were obtained by CRISPR/Cas9-mediated deletion of DMD exon 50 in unaffected cells generated from healthy donor and then differentiated into cardiomyocytes (hiPSC-CM). The latter were subjected to global transcriptomic and proteomic analyses followed by more in-depth investigation of selected pathway and pharmacological modulation of observed defects. Proteomic analysis indicated a decrease in the level of mitoNEET protein in dystrophin-deficient hiPSC-CM, suggesting alteration in iron metabolism. Further experiments demonstrated increased labile iron pool both in the cytoplasm and mitochondria, a decrease in ferroportin level and an increase in both ferritin and transferrin receptor in DMD hiPSC-CM. Importantly, CRISPR/Cas9-mediated correction of the mutation in the patient-derived hiPSC reversed the observed changes in iron metabolism and restored normal iron levels in cardiomyocytes. Moreover, treatment of DMD hiPSC-CM with deferoxamine (DFO, iron chelator) or pioglitazone (mitoNEET stabilizing compound) decreased the level of reactive oxygen species in DMD hiPSC-CM. To our knowledge, this study demonstrated for the first time impaired iron metabolism in human DMD cardiomyocytes, and potential reversal of this effect by correction of DMD mutation or pharmacological treatment. This implies that iron overload-regulating compounds may serve as novel therapeutic agents in DMD-associated cardiomyopathy.

IRON DEFICIENCY WITH AND WITHOUT ANEMIA IN PATIENTS OF HEART FAILURE WITH REDUCED EJECTION FRACTION

Iron deficiency (ID) is the most common dietary deficiency in the world and the leading cause of anemia. Iron deficiency can lead to symptoms both due to the lack of iron and due to the resultant anemia. Heart failure patients can develop iron deficiency (ID) by various mechanisms. Considering that iron levels may vary in different geographical regions according to economic, environmental, infectious, and genetic factors, this study was particularly devoted for studying iron deficiency in heart failure patients irrespective of presence of anemia. Patients >18 years diagnosed with heart failure on the basis of clinical and biochemical parameters and an ejection fraction ≤40% on transthoracic echocardiography were recruited and biochemical parameters and iron profile was analysed for the presence of iron deficiency. The study subjects' mean ejection fraction was 35.02±4.56%. The mean age was 59.33± 14.06 years. The study involved 90 patients, of whom 69 (76.7%) were classified as iron deficient because their S. ferritin levels were less than 100 μg/L and/or their transferrin saturation was less than 20%. The remaining 21 patients were classified as having normal iron levels. NT pro-BNP was significantly higher in iron deficient cases than those with normal iron (7822±7047 vs. 2673±1806 pg/ml). In the present study 76.7% of individuals with heart failure and a decreased ejection fraction had iron insufficiency. Further studies with larger sample size to correlate grades of HF with ID strata are recommended. This has got therapeutic potential and lays scaffold for prospective studies.

Impact of low serum iron on treatment outcome of PD-1 inhibitors in advanced gastric cancer

BackgroundThe aim of this study was to investigate the influence of serum iron levels in advanced gastric cancer (GC) patients treated with programmed cell death protein-1 (PD-1) inhibitors.MethodsWe retrospectively reviewed 149 GC patients who were treated with PD-1 inhibitors at our center. Clinicopathological characteristics, laboratory data, and clinical outcomes were analyzed.ResultsMultivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), histological subtype, and baseline serum iron levels were independent prognostic factors for overall survival (OS), while ECOG PS, multiple metastatic sites, and baseline serum iron levels were independent prognostic factors for progression-free survival (PFS). Patients with baseline low serum iron levels (LSI) had a significantly shorter median OS and PFS compared to patients with normal serum iron levels (NSI) (Median OS: 7 vs. 14 months, p = 0.001; median PFS: 3 vs. 5 months, p = 0.005). Patients with baseline LSI had a disease control rate (DCR) of 58.3% at 2 months after PD-1 inhibitor initiation (M2), compared to 81.1% in patients with NSI (p = 0.005). Patients with baseline LSI had a DCR of 43.8% at 4 months, compared to 64.2% in patients with NSI (p = 0.017).ConclusionsLSI was associated with worse OS, PFS, and DCR in GC patients treated with PD-1 inhibitors and might be a quick and efficient biomarker to predict the efficacy of PD-1 inhibitors.

Rusfertide Improves Markers of Iron Deficiency in Patients with Polycythemia Vera

Background: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis defined by an acquired increase in hemoglobin (Hb)/hematocrit (HCT). Disease complications are associated with increased blood viscosity, cardiovascular/thrombotic events and iron deficiency (Marchioli et al. N Engl J Med. 2013;368:22-33). Most patients with PV are iron deficient and therapeutic phlebotomy may exacerbate iron deficiency (Ginzburg et al. Leukemia. 2018;32:2105-16). Methods:PTG-300-08 (clinicaltrials.gov NCT04767802, PACIFIC study) is an open-label, 52-week, phase 2 study that investigated the efficacy and safety of rusfertide in Asian patients with poor hematocrit (HCT) control as noted by HCT >48%. Treatment was initiated with 40 mg rusfertide subcutaneously (SC) twice a week. Once HCT was <45%, the treatment was changed to 40 mg once a week with subsequent dose adjustments allowed to maintain HCT <45%. In addition to HCT and erythrocyte morphology (mean corpuscular volume, or MCV), biomarkers reflective of iron biology, such as hepcidin, erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR) were measured at baseline, Week 4, 16, and 32 following initiation of rusfertide treatment. To examine the effect of rusfertide on serum iron, patients were stratified by baseline ferritin levels to examine patients who were iron deficient (ferritin ≤20 µg/L) compared to patients who had normal iron (ferritin >20 µg/L). Results: Twenty patients (15 males, 5 females), average age 56.7 (SD, 9.12) years and average weight 65 (10.9) kg were enrolled. Thirteen patients (65%) were low risk and 7 (35%) were high risk, all based on age. No patients had a prior history of thromboembolic events. Mean duration since PV diagnosis was 4.2 (3.83) years. Rusfertide rapidly and robustly reduced mean HCT and sustained HCT <45% for the duration of treatment, and ferritin, TSAT and MCV increased (Table 1). At baseline, 30% of subjects had serum ferritin levels below 20 µg/L, with all subjects achieving and sustaining ferritin levels above 20 µg/L by Week 4 following initiation of rusfertide treatment. Table 1 also summarizes the biomarkers related to iron indices. Median hepcidin concentrations increased, median EPO concentration was below and remained below the limit of detection, and ERFE concentration decreased modestly with rusfertide dosing consistent with reduced erythropoietic drive. Among patients with evidence of baseline iron deficiency (ferritin <20 µg/L), rusfertide normalized iron levels while iron levels remained stable in rusfertide patients with normal iron levels at baseline (Figure 1). Similarly, patients with iron deficiency had low MCV at baseline (Figure 1) which increased following initiation of rusfertide treatment. In patients with normal iron levels, MCV remained stable in the normal range (>80 fl). Conclusions: Treatment with rusfertide resulted in rapid, robust, and sustained reduction in HCT levels in PV patients with elevated HCT levels at baseline. Treatment resulted in normalization of iron parameters as noted by increases in ferritin, and normalization of serum iron and MCV in patients who were iron deficient at baseline. Improvements in iron deficiency following rusfertide are suggestive of clinical benefits and merit further investigation. This analysis confirms the general understanding that managing iron deficiency in PV remains an unmet need.

Liver Iron Overload Drives COVID-19 Mortality: a Two-Sample Mendelian Randomization Study.

Iron overload has been associated with an increased risk of COVID-19 severity and mortality in observational studies, but it remains unclear whether these associations represent causal effects. We performed a two-sample Mendelian randomization (MR) to determine associations between genetic liability to iron overload and the risk of COVID-19 severity and mortality. From genome-wide association studies of European ancestry, single-nucleotide polymorphisms associated with liver iron (n = 32,858) and ferritin (n = 23,986) were selected as exposure instruments, and summary statistics of the hospitalization (n = 16,551) and mortality (n = 15,815) of COVID-19 were utilized as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis to estimate causal effects, and other alternative approaches as well as comprehensive sensitivity analysis were conducted for estimating the robustness of identified associations. Genetically predicted high liver iron levels were associated with an increased risk of COVID-19 mortality based on the results of IVW analysis (OR = 1.38, 95% CI: 1.05-1.82, P = 0.02). Likewise, sensitivity analyses showed consistent and robust results in general (all P > 0.05). A higher risk of COVID-19 hospitalization trend was also observed in patients with high liver iron levels without statistical significance. This study suggests that COVID-19 mortality might be partially driven by the iron accumulation in the liver, supporting the classification of iron overload as one of the independent death risk factors. Therefore, avoiding iron overload and maintaining normal iron levels may be a powerful measure to reduce COVID-19 mortality.

FRI326 Hypophysitis: A Formidable Diagnostic Challenge

Abstract Disclosure: S. Pandey: None. C. Houston: None. Background: Hypophysitis, defined as inflammation of the pituitary gland, may pose a formidable diagnostic challenge due to its protean clinical manifestations and growing spectrum of potential causes. We present a case of a young man with presumed hypophysitis in whom the etiology remains unknown. Case Summary: A previously healthy 20-year-old male with bilateral gynecomastia was referred to the endocrinology clinic. He reported a 1-year history of worsening fatigue, weight gain, intermittent headaches, bilateral breast enlargement, lack of morning erections, polydipsia, and polyuria. His childhood growth and pubertal development were reportedly normal. He denied prior head or testicular trauma, major systemic illnesses, and chronic opiate or glucocorticoid use. His physical exam was remarkable only for scant facial hair and bilateral nontender gynecomastia. His visual fields were normal, and sense of smell was intact. Laboratory evaluation at 8am revealed low total and free testosterone of 32 ng/dL (240-950) and 0.98 ng/dL (5.25-20.7), respectively, with LH of 1.4 mIU/mL (1.0-12.0) and FSH of 1.9 mIU/mL (1.0-12.0). Free T4, prolactin, IGF-1, and serum sodium were all within normal ranges. Serum cortisol was modestly elevated at 22.3 ug/dL (3.7-19.4) with normal ACTH of 49 pg/mL (7.2-63.0). Pituitary MRI showed diffuse thickening and enhancement of the pituitary stalk, compatible with infundibular hypophysitis, without evidence of mass effect upon the native gland or surrounding structures. Additional testing showed normal levels of serum calcium, iron, ferritin, ESR, and antinuclear antibodies. After overnight water deprivation, his serum sodium was elevated at 156 mmol/L (134-144) with low urine osmolality of 121 mOsmol/kg (300-900). He was started on desmopressin and testosterone, and close clinical monitoring was enacted. Conclusion: The diagnosis of hypophysitis poses multiple challenges. Its clinical manifestations can vary widely, including symptoms related to mass effect and/or symptoms of pituitary dysfunction. Diagnosis is often presumptive based on history and exam, biochemical evaluation, and neuroimaging. The spectrum of potential causes is broad and growing, including infiltrative, infectious, neoplastic, immunoglobulin G4-related, immunotherapy-induced, other autoimmune, and paraneoplastic causes. It is often a humbling experience for clinicians to narrow this exhaustive differential. Pituitary biopsy is the gold standard for diagnosis but poses significant risks, so is reserved for cases when the diagnosis remains uncertain or malignancy is suspected. Close clinical monitoring and re-evaluation is an acceptable alternative in select cases. Presentation: Friday, June 16, 2023

THU368 A Rare Case Of Glycogenic Hepatopathy With Persistent Lactic Acidosis

Abstract Disclosure: M. Shah: None. S. Challagulla: None. Background: Glycogenic hepatopathy (GH) is an under-recognized complication of poorly controlled diabetes. It is caused by abnormal glycogen accumulation in hepatocytes leading to hepatomegaly and transient elevation of liver transaminases. Diagnosis is often delayed as liver biopsy is needed to distinguish it from other causes of liver injury. Complete resolution can be achieved with intensive glucose control. We present a case of GH diagnosed in a patient who developed increasing liver transaminases and persistent lactic acidosis after resolution of DKA. Clinical Case: We present a 21-year-old female with uncontrolled Type 1 diabetes who presented with fatigue, nausea, and generalized body aches. Patient was hemodynamically stable. Laboratory work up on admission showed a serum glucose of 834 mg/dL, serum bicarbonate less than 5 mEq/L, beta hydroxybutyrate was elevated to 8.7 mmol/L (normal <0.4 mmol/L), lactic acid was also elevated to 7.9 mmol/L (normal <2.0 mmol/L). She was diagnosed with DKA and treated with IV fluids and insulin drip. Over the next five days the patient’s symptoms improved and DKA resolved with beta hydroxybutyrate falling to <0.1 mmol/L. Her lactic acidosis however persisted, she had no apparent infection and no episodes of hypotension to explain this finding. CT scan of the abdomen revealed hepatomegaly not compatible with steatosis. Liver enzymes on admission were mildly elevated AST 57 IU/L and ALT 61 IU/L however values continued to rise and peaked at AST 2372 IU/L and ALT 681 IU/L five days later. Further laboratory studies revealed no evidence of viral hepatitis, no presence of drugs or toxins. Chronic liver disease work up revealed normal ANA, AMA, SPEP, ceruloplasmin, and iron levels. Patient ultimately underwent liver biopsy which revealed glycogenic hepatopathy, mild steatosis, and mild fibrosis. Patient’s lactic acidosis eventually improved with supportive care, and she was discharged. On follow up 3 months later the patient's liver enzymes had returned to normal. Discussion: Glycogenic hepatopathy is a rare diagnosis usually seen in patients with uncontrolled diabetes and elevated liver transaminases. It is hypothesized that pathogenesis of GH involves insulin increasing glycogen synthesis in the liver resulting in congested hepatocytes. Persistent lactic acidosis can also be seen; it has been proposed that increased insulin and dextrose administration prevents gluconeogenesis in the liver, therefore decreased conversion of pyruvate to glucose and increased lactate production. GH is important to understand and differentiate from other causes of liver injury and disease as treatment and prognosis is unique. Prompt liver biopsy should be pursued to elucidate diagnosis of GH. If patients are treated with aggressive glycemic control, hepatopathy can completely resolve. Presentation: Thursday, June 15, 2023

The Effect of Iron Overload on the Mobilization of Peripheral Blood Hematopoietic Stem Cells in Pediatric Patients with Thalassemia Major

Introduction: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with β-thalassemia major (TM). Methods: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. Results: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34⁺ cell levels (all, p < 0.05). Conclusion: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.

Bone-derived C-terminal FGF23 cleaved peptides increase iron availability in acute inflammation

AbstractInflammation leads to functional iron deficiency by increasing the expression of the hepatic iron regulatory peptide hepcidin. Inflammation also stimulates fibroblast growth factor 23 (FGF23) production by increasing both Fgf23 transcription and FGF23 cleavage, which paradoxically leads to excess in C-terminal FGF23 peptides (Cter-FGF23), rather than intact FGF23 (iFGF23) hormone. We determined that the major source of Cter-FGF23 is osteocytes and investigated whether Cter-FGF23 peptides play a direct role in the regulation of hepcidin and iron metabolism in response to acute inflammation. Mice harboring an osteocyte-specific deletion of Fgf23 showed a ∼90% reduction in Cter-FGF23 levels during acute inflammation. Reduction in Cter-FGF23 led to a further decrease in circulating iron in inflamed mice owing to excessive hepcidin production. We observed similar results in mice showing impaired FGF23 cleavage owing to osteocyte-specific deletion of Furin. We next showed that Cter-FGF23 peptides bind members of the bone morphogenetic protein (BMP) family, BMP2 and BMP9, which are established inducers of hepcidin. Coadministration of Cter-FGF23 and BMP2 or BMP9 prevented the increase in Hamp messenger RNA and circulating hepcidin levels induced by BMP2/9, resulting in normal serum iron levels. Finally, injection of Cter-FGF23 in inflamed Fgf23KO mice and genetic overexpression of Cter-Fgf23 in wild type mice also resulted in lower hepcidin and higher circulating iron levels. In conclusion, during inflammation, bone is the major source of Cter-FGF23 secretion, and independently of iFGF23, Cter-FGF23 reduces BMP-induced hepcidin secretion in the liver.

5575938 DIETARY PATTERN, SOCIO-DEMOGRAPHIC CHARACTERISTICS AND NUTRITIONAL STATUS OF PREGNANT WOMEN ATTENDING BARAU DIKKO TEACHING HOSPITAL AND THE NEED TO DEVELOP RECOMMENDED DIETARY ALLOWANCE AND DIETARY REFERENCE INTAKES FOR SICKLE CELL DISEASE PATIENTS

Background: Micronutrient deficiencies, particularly lack of vitamin A, iron and iodine have severe adverse effect on women and children (Lopriore and Muehlhoff, 2005). More resources need to be dedicated to research so as to establish a standard and specific recommended dietary allowance (RDA’s) for SCD patients, like the one developed for the general population (Beatrice et al, 2010). Lack of screening plays a major part in excessive mortality and a lot of the life threatening complications of SCD among under 5 children have well established nutritional basis. Impairment of immune response among children with SCD is largely associated with poor nutritional status and this drives infection related mortality. Nutritional status has been shown to be critical in SCD severity, weight for age score was shown to significally predict hospitalization in SCD. (Mohammad et al, 2001). In this study, the dietary pattern, nutritional status and micronutrient status of pregnant women attending Barau Dikko Teaching Hospital (BDTH), Kaduna were assessed. Aims: Assess the dietary pattern and nutritional status of pregnant women attending BDTH, Kaduna Determine the micronutrient status (Vitamin A, Iron and Zinc) during pregnancy To state the link between nutrition and SCD Methods: 180 apparently healthy pregnant women attending antenatal clinic at BDTH were involved in the research. Informed consent was sought from all pregnant women. Food frequency questionnaire (FFQ) was used to assess food intake, mid-upper arm circumference (MUAC) was used to assess nutritional status, serum zinc and iron content were analysed using atomic absorption spectrophotometry (AAS) and vitamin A was analysed spectrophotormetrically. Data were analysed and presented using the statistical package for social sciences (SPSS) software version 20.0 for descriptive statistics, statistical significance was set at p<0.05. Results is presented as mean ± SD. Results: The age range of the pregnant women was mostly between 30-34 years. Most women had secondary school education. They were predominantly full time house wives. Maize was the most commonly food consumed by 69/180 pregnant women (38.5%). 140 pregnant women (78%) have normal serum iron levels while 40 pregnant women (22%) have low values (<10.74 µmol/L), though iron supplementation was given. Serum zinc levels were low (7.36 ± 0.31 1st trimester, 7.28 ± 0.37 2nd trimester, 7.18 ± 0.56 3rd trimester), serum vitamin A levels (1.67 ± 0.16 1st trimester, 1.53 ± 0.12 2nd trimester, 1.49 ± 0.11 3rd trimester). Severe acute malnutrition mainly occurred in the third trimester, 36/180 (20%) pregnant women. Conclusion: This study has established that higher percentage of malnutrition occurred in the third trimester (20%) pregnant womwen which may be due to the fœtus drawing a lot of nutrient from the mother. The dietary pattern showed a high frequency of consumption of carbohydrate food groups. Anthropometry of the pregnant women showed severe acute malnutrition (20%) in the 3rd trimester. The nutritional status of pregnant women is associated with birth weight of the baby. Baby given birth to by poorly nourished mother has a lower body weight as compared to the baby of better nourished mothers (Gashew et al 2019). Research have shown weather a pregnant woman is sickle or not there is an adverse effect on the new born if she is malnourished and also great consequences if the newborn is sikcle (Brown et al, 1994).

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

The Continued Need for the Routine Assessment of Folate Status.

The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. Atotal of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

A STUDY OF ASSOCIATION OF LOW IRON STATUS AND FEBRILE SEIZURES IN CHILDREN AGED 6 MONTHS TO 60 MONTHS

Background: Febrile seizures are the most common type of childhood seizures. The peak incidence is at 18 months of age. Iron deciency alters the development of the hippocampus, neurons, delayed myelin maturation, slowing of auditory and visual evoked potentials, impairment of energy metabolism, alteration in synaptic neurotransmitter which lessens the seizure threshold. These effects are aggravated during febrile episodes thereby increasing the risk of occurrence of febrile seizures. To know the association Objective: between low iron status with or without anemia and febrile seizures. A tot Results: al of 111 children with febrile seizures were taken into study. Among them, 68 children (61.1%) had low serum iron levels and 43 (38.7%) children had normal serum iron levels. Iron deciency anemia was found in 46 (41.4%) of them. Low iron status even without the development of anemia increa Conclusion: ses the risk of febrile seizures through various nonhematological manifestations of iron deciency.

Pre and Early Post-Operative Iron Assessment in Obese Patients Underwent Laparoscopic Sleeve Gasterctomy

Obesity is a chronic disease associated with mortality and morbidity. Bariatric surgery (BS) as a long-term weight reduction treatment has been increased. This study investigated the early state of iron storage and deficiency in patients underwent laparoscopic sleeve gastrectomy (LSG). Thirty patients were selected as a prospective study underwent LSG according to specialized inclusion and exclusion criteria at Soran Private Hospital in Erbil, from 1/1/2021 to 1/9/2021 after signing a consent form. All selected patients underwent preoperative and three months’ post-operative hemoglobin (Hb), mean corpuscular volume (MCV), and serum ferritin (SF) assessments. They were instructed to follow specialized diet regimen for three months’ post-operative and not to take any drugs and supplements. Results showed a strong positive correlation between preoperative and postoperative assessment for both Hb and MCV respectively (r= 0.72; P &lt; 0.001), (r= 0.76; P &lt; 0.001), and a moderate correlation for SF (r= 0.41; P &lt; 0.024). Significant difference (P &lt; 0.05) was found between preoperative and postoperative for the three markers (Hb, MCV and SF). Their values were decreased from preoperative to postoperative for the majority of the cases, but they were still within the normal range. The finding demonstrated that after three months from LSG, no patients showed iron deficiency anaemia. However, there was decrease in SF level which indicated that the storage capacity of iron was decreasing. This suggest that the iron supplement has to be started since the food regime followed in by the patients was not sufficient to maintain normal iron level.

The Role of Iron and Cobalt in Gynecological Diseases.

Iron and cobalt are micronutrients that play an important role in the regulation of cellular processes, being part of the centre of catalases, peroxidases, cytochromes and metalloproteins such as hemoglobin and myoglobin (Fe). Cobalt primarily functions as a component of hydroxycobalamin, which is essential for regulating red blood cell production. Maintaining normal levels of cobalt and iron in the human body is important, as a deficiency can lead to anaemia. These elements are also involved in reactions during which oxidative stress occurs and are therefore considered to be a cause of tumor formation. This paper will discuss aspects of the influence of cobalt and iron on mechanisms that may contribute to the growth of gynecological tumors, as well as other obstetric-gynecological disease entities, by altering the conditions of the microenvironment. In addition, the following review also highlights the role of cobalt and iron in the treatment of gynecological tumors.