Changes In Serum Iron Levels Research Articles

Association between urinary phthalate metabolites and Anemia in US adults

Initial research indicates a possible connection between exposure to phthalates and the development of anemia. To fill the gap in epidemiological data, our study utilized data from across the United States, representative on a national scale, to evaluate the association between the concentration of phthalate metabolites in urine and both anemia and iron levels. We gathered data on 11,406 individuals from the National Health and Nutrition Examination Survey (NHANES) database, spanning 2003–2018. We conducted logistic and linear regression analyses, adjusted for potential confounding factors, to evaluate the correlations between different phthalate metabolites and anemia, as well as serum iron levels, including gender-stratified analysis. Most urinary phthalate metabolites were positively correlated with an increased risk of anemia, and the majority were negatively correlated with serum iron levels. The study revealed that for every unit increase in ln-transformed metabolite concentrations, the odds ratios (ORs) for anemia increased to varying degrees, depending on the phthalate: Monobutyl phthalate (MBP) at 1.08 (95% CI 1.01–1.17, P = 0.0314), mono(3-carboxypropyl) phthalate (MCPP) at 1.17 (95% CI 1.10–1.24, P < 0.0001), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) at 1.08 (95% CI 1.02–1.15, P = 0.0153), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) at 1.14 (95% CI 1.07–1.21, P < 0.0001), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) at 1.11 (95% CI 1.03–1.18, P = 0.0030), monocarboxynonyl phthalate (MCNP) at 1.11 (95% CI 1.03–1.19, p = 0.0050), and monocarboxyoctyl phthalate (MCOP) at 1.13 (95% CI 1.07–1.19, P < 0.0001). Increased levels of MBP, MEHP, MBzP, MCPP, MEHHP, MEOHP, MIBP, MECPP, MCNP, and MCOP were linked with changes in serum iron levels, ranging from − 0.99 µg/dL (95% CI − 1.69 to − 0.29) to − 3.72 µg/dL (95% CI − 4.32 to − 3.11). Mixed-exposure analysis shows consistency with single-exposure model. Further mediation analysis showed that the association between single urinary phthalates and the risk of anemia was mediated by serum iron with a mediation ratio of 24.34–95.48% (P < 0.05). The presence of phthalate metabolites in urine shows a positive correlation with the prevalence of anemia, which was possibly and partly mediated by iron metabolism. Nonetheless, to confirm a definitive causal link and comprehend the underlying mechanisms of how phthalate exposure influences anemia, additional longitudinal and experimental research is required.

Impact of Acid Suppression Therapy on Iron Supplementation in the Pediatric Intensive Care Unit.

We assessed the impact of acid suppression therapy (i.e., ranitidine or proton pump inhibitors) on iron supplementation and its ability to maintain or alter laboratory values that are commonly associated with anemia. This was a prospective, observational trial. The primary outcome was changes in serum iron levels from baseline. Secondary outcomes were changes in hemoglobin (Hgb) and hematocrit (Hct), transfusions, and maintenance of an alkalotic gastric pH. Thirty-four patients (mean 24 ± 43 months) met inclusion criteria. The serum iron levels increased to 50.9 ± 24.6 mcg/dL by day 3. The mean difference from baseline was 1.5 mcg/dL (95% CI, 1.14-1.98, p = 0.0056). Gastric pH increased to 4.68 ± 1.49 on day 5. The mean Hgb and Hct increased on day 5 to 10 ± 1.06 g/dL and 29.6% ± 3.27%, respectively. The mean difference of Hgb was 1.15 g/dL (95% CI, 0.51-1.78, p = 0.0009). The mean difference of Hct was 3.04% (95% CI, 1.11-4.97, p = 0.0032). The use of antacids along with oral ferrous sulfate supplementation did not affect the absorption of iron. Serum iron, Hgb, and Hct all showed statistically significant increases despite combined antacid and iron therapy. Thus, despite use of antacids, combination use showed increases in iron absorption.

Ocular toxicity of AUY922 in pigmented and albino rats

AUY922, a heat shock protein 90 inhibitor is associated with ocular adverse events (AEs). To provide a better understanding of ocular AEs in patients, 4 investigative studies were performed in a step-wise approach to assess retinal structure and function in pigmented (Brown Norway) and albino (Wistar) rats. In rats administered 30mg/kg of AUY922, the AUC0–24h and Cmax are comparable to that in patients at 70mg/m2. AUY922 at ≥30mg/kg was poorly tolerated by rats with morbidity or mortality generally after the third weekly treatment. Electroretinography (ERG) changes were observed at doses ≥30mg/kg. The ERG changes were dose dependent, consistent with an effect on the photoreceptors, and fully reversible. The ERG effects could not be minimized by decreasing the Cmax while maintaining AUC. Histopathological changes were seen mainly when rats were administered AUY922 at 100mg/kg. The 2-hour infusion of AUY922 at 100mg/kg caused disorganization of the outer segment photoreceptor morphology in male Brown Norway rats; the severity of the disorganization increased with the number of administrations, but was reversible during a 4-week posttreatment period. There was no major difference in ocular response between Brown Norway and Wistar rats. No changes in serum iron levels, and no changes in rhodopsin, PDE6α, β-transducin concentrations, or retinal pigment epithelium-specific protein RPE65 expression were observed after single and multiple infusions of AUY922 at 100mg/kg compared to vehicle-treated controls. AUY922 retinal toxicity in rats recapitulates and further characterizes that reported in patients and is shown to be reversible, while a precise molecular mechanism for the effect was not determined.

Decorporation of Iron Metal Using Dialdehyde Cellulose-Deferoxamine Microcarrier

Deferoxamine iron chelator has a limited therapeutic index due to rapid clearance from blood and possesses dose-limiting toxicity. Therefore, an intravenous deferoxamine delivery system based on dialdehyde cellulose (DAC) polymer was developed and its efficacy and toxicity were tested in iron-overloaded animals. The amino groups of deferoxamine were conjugated to free aldehyde moieties of dialdehyde cellulose via Schiff base reaction to form dialdehyde cellulose-deferoxamine (DAC-DFO) conjugate and characterized by Fourier transform infrared spectrophotometer, scanning electron microscope, and X-ray diffraction. The toxicity of prepared formulation was analyzed by XTT cell viability assay and LD50 study in mice. The change in serum iron levels, after intravenous administration of formulation, was observed in iron-overloaded rats. The DAC-DFO conjugate was tagged with Tc-99m to study the blood kinetics and observe change in blood circulation time. DAC-DFO conjugate was dispersible in water at concentration ∼75mg/ml. In vitro cytotoxicity assay and LD50 study in mice indicated significantly enhanced safety of covalently bound deferoxamine (at >1000mg/kg body weight compared to free drug at ∼270mg/kg dose). A preliminary scintigraphy imaging and blood clearance study, with technetium-99m, indicated prolonged circulation of conjugated DFO in rabbit blood. A single dose of formulation injected into iron overloaded animals was found to maintain the normal serum iron levels until 10days. The polymeric conjugate was effective in maintaining normal serum iron levels until 10days at a dose of 100mg/kg body weight.

Outcomes of long-term iron supplementation in pediatric restless legs syndrome/periodic limb movement disorder (RLS/PLMD)

ObjectivesRestless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are thought to center around a genetically mediated sensitivity to iron insufficiency. Previous studies have shown the effectiveness of short-term iron therapy in children with low iron storage. Little is known, however, about long-term iron treatment in children with RLS and PLMD. Therefore, we performed this study to assess the long-term effect of iron therapy in children with RLS and PLMD. MethodsA retrospective chart review was performed for children who met the following criteria: A) diagnosed as having either RLS or PLMD, B) started on iron supplementation, C) followed up for >2 years in a sleep clinic. Baseline values for iron, ferritin, and periodic limb movement of sleep index (PLMS index) were defined in the three months leading up to the initiation of iron therapy. Values were also computed for follow-up periods of 3–6 months, 1–2 years, and >2 years. Serum iron and ferritin levels and PLMS index were compared between baseline and all subsequent follow-ups. ResultsIn total, 105 patients met inclusion criteria, of whom 64 were diagnosed with PLMD alone, seven with RLS alone, and 35 with both RLS and PLMD. The average age was 10.2 ± 5.3 years. Compared to the baseline (27.4 ± 12.1 ng/ml), the average ferritin values at 3–6 months (45.62 ± 21.2 ng/ml, p < 0.001, n = 34), 1–2 years (52.0 ± 48.3 ng/ml, p < 0.001, n = 63), and >2 years (54.7 ± 40.5 ng/ml, p < 0.001, n = 67) were all significantly increased. Inversely, compared to baseline (21 ± 27.0/h, n = 66), PLMS index values at 3–6 months (7.5 ± 9.5/h p < 0.05, n = 11), 1–2 years (6.9 ± 8.9/h, p < 0.001, n = 29), and >2 years (10 ± 14.5/h, p < 0.001, n = 31) were all significantly decreased. No significant change in serum iron levels was noted at any time point. ConclusionWhile retrospective in nature, this study demonstrates a sustained improvement in PLMS index and maintenance of adequate ferritin levels >2 years after iron therapy initiation in our RLS/PLMD cohort with a long-term follow-up. Iron therapy appears to lead to long-lasting improvements in children with RLS/PLMD.

Longer Duration of Red Blood Cell Storage Induces Progressively Increased Markers of Extravascular Hemolysis and Hepcidin in Autologously Transfused Healthy Volunteers

Background:Transfusion of stored red blood cells (RBCs) results in a variable amount of extravascular hemolysis depending on the extent of RBC damage during storage. Metabolomic studies of RBCs throughout storage in vitro suggest that a shift in the metabolomics profile occurs at 14-21 days of storage; however, the correlation between storage duration in vitro and the extent of hemolysis in vivo is unknown.Aims:This study examined the relationship between storage duration and laboratory evidence of hemolysis in human recipients after autologous RBC transfusion.Methods:We recruited 30 healthy adults who met the standards for allogeneic blood donation. Each volunteer was randomized to receive a transfusion of one autologous RBC unit after 1, 2, 3, 4, 5, or 6 weeks of storage. Each RBC unit was transfused over 1 hour and blood samples were collected before, and at 0, 2, 4, 8, 10, 12, 14, and 20 hours after transfusion to measure various analytes. Serum hepcidin was measured by ELISA, plasma free hemoglobin by the cyanomethemoglobin method, and all other parameters by standard clinical laboratory assays. For each analyte, the Pearson correlation coefficient was used to determine the strength of the linear association between storage duration and changes in analyte levels at specific times post-transfusion.Results:At each time evaluated between 0 and 8 hours after transfusion, indirect bilirubin, a marker of extravascular hemolysis, progressively and linearly increased proportionally with RBC storage duration, with the maximal regression coefficient observed 2 hours post-transfusion (R2 = 0.44; p<0.0001). Furthermore, at all times evaluated between 0 and 14 hours post-transfusion, serum iron increased proportionally with storage duration (see Figure); the strongest regression coefficient was observed 6 and 8 hours post-transfusion (R2 = 0.67; p<0.0001). In conjunction with the increases in serum iron, hepcidin, the master regulator of iron homeostasis, increased proportionally with storage duration at all times between 6 and 12 hours post-transfusion with a maximal regression coefficient at 8 hours post-transfusion (R2 = 0.25; p<0.007). In contrast, no linear associations were found between RBC storage duration and indicators of intravascular hemolysis, including plasma free hemoglobin, lactate dehydrogenase, and haptoglobin.Conclusion:Altogether, these results suggest that, as storage duration increases, there is a progressive increase in post-transfusion extravascular hemolysis. Furthermore, this is the first report of an effect of stored RBC transfusions on serum hepcidin concentrations. In particular, progressive increases in hepcidin levels, associated with increased storage duration, are observed starting at 6 hours post-transfusion. Nonetheless, the strengths of correlation coefficients between markers of extravascular hemolysis and RBC storage duration suggest that substantial donor/recipient variability exists. The clinical consequences of the progressive increase in extravascular hemolysis with greater durations of RBC storage remain to be determined.Median with interquartile range for changes in serum iron levels from baseline (i.e., pre-transfusion) to 20 hours post-transfusion for each randomized week of RBC storage (N=30). Serum iron increased between 0 and 14 hours post-transfusion, with a maximum peak at 6-8 hours post-transfusion. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Ectoparasite infestation patterns, haematology and serum biochemistry of urban‐dwelling common brushtail possums

Urban environments support high concentrations of humans, domestic pets and introduced animals, creating conditions conducive to the transmission of parasites. This study compared patterns of ectoparasite infestation of the common brushtail possum Trichosurus vulpecula in urbanised Sydney (n = 161) to those from a remote woodland site (n = 18) from February 2005 – November 2006. We found diff erences in ectoparasite species prevalence between the two groups: the flea Echidnophaga myrmecobii was only found on urban possums and the tick Ixodes trichosuri was much more prevalent in the urban habitat, while the mite Atellana papilio was more prevalent on woodland possums. E. myrmecobii and I. trichosuri diff ered from other ectoparasites by showing an association with host sex and host age. Potential physiological costs of ectoparasitism to urban‐dwelling possums were determined using multivariate analysis of haematology, serum biochemistry and body condition. Changes in serum iron levels were seen in the presence of both the tick Ixodes trichosuri and the flea E. myrmecobii, and E. myrmecobii was associated with elevated serum levels of the liver enzyme ALT. However, ectoparasite‐related changes in haematology and serum biochemistry were not indicative of long‐term pathology. In this urban possum population, the costs of ectoparasitism appear to be limited and unlikely to pose a major threat to the health of the population.

Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: A conceptual framework

Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection.

Estrogens Iron Out the Details: A Novel Direct Pathway for Estrogen Control of Iron Homeostasis

The importance of estrogens and iron to physiology and disease has been known for decades, and their levels are intentionally manipulated throughout human life whether by doctor’s prescriptions or over-the-counter natural supplements. An important and often overlooked detail is that these two factors interact. This interaction largely consists of estrogen effects on menstrual blood flow, a major source of iron loss in premenopausal women (1, 2). However, in a recent publication in Endocrinology, the lab of Xi Huang describes a direct mechanism of interaction between estrogens and hepcidin, the peptide hormone that regulates iron transport and homeostasis. Specifically, they observed that estrogen can decrease the expression of hepcidin mRNA by an estrogen response element half-site upstream in the hepcidin promoter (3). Iron is an essential trace element that is required for human life and tightly regulated in the plasma between 10–30 M (4). Iron homeostasis is maintained by altering the absorption of iron from the gut and the release of iron from storage in hepatocytes and macrophages. A key regulator of these processes is hepcidin, a 25-amino acid peptide hormone produced by the liver to inhibit iron transport by binding and inhibiting the cellular iron exporter, ferroportin. A brief schematic of the role of hepcidin in iron homeostasis is shown in Fig. 1. The levels of hepcidin are regulated in a homeostatic manner so that high iron levels raise hepcidin to decrease iron absorption and lower the rate of release from storage cells (4, 5). The reproductive axis in women affects iron homeostasis in part through menstrual blood flow. Because iron is tightly conserved with low levels of excretion, menstrual blood flow represents a significant source of iron loss from the body (1, 2). Premenopausal nonpregnant women are often deficient in iron, and postmenopausal women have higher levels of iron (3) and a much lower recommended daily allowance of iron intake (1). Iron levels are also raised in women who take oral contraceptives (6, 7). Although this effect may be due to smaller volume of menstrual blood flow, a similar effect occurs in rats that do not lose blood with menses (8). The recent study by Yang et al. (3) describes a mechanism by which estradiol could increase iron absorption and iron release from storage cells. Specifically, the authors describe a functional estrogen response element (ERE) half-site in the human hepcidin promoter, and they observe that 24 h after estradiol treatment, hepcidin mRNA are decreased both in vitro in human liver cells and in vivo in mice. An estrogen antagonist (ICI 182,780) prevented the estradiol-induced decrease and, independent of estradiol treatment, caused an increase in hepcidin mRNA that indicates that the estrogen receptor may have ligandindependent effects on hepcidin expression. It remains to be seen whether the effect of estradiol on hepcidin expression is robust enough to substantially alter iron homeostasis in vivo. Although the magnitude of the effect on hepcidin mRNA was substantial (up to 50% in HuH7 cells), the estradiol-induced decrease in liver hepcidin mRNA did not correspond with an effect on serum iron concentration in mice. However, all measurements were taken only 24 h after estradiol injection (3). Therefore, it is possible that an effect would have been observed with chronic estradiol treatment. Because hepcidin is the principal regulator of iron distribution as well as absorption, it’s also possible that the effects may alter tissue distribution without a change in serum iron levels. In humans, the relationship between exogenous estrogen treatment and iron homeostasis is not clear. Women using oral contraceptives have higher levels of iron (6, 7),

Anemia in cats infected by Trypanosoma evansi

One of the main characteristics of the trypanosomosis is the development of anemia, although its pathogenesis still remains unclear. Therefore, the objective of this study was to discuss the possible pathogenesis of anemia in the infection by Trypanosoma evansi in cats. A study using an experimental model with T. evansi-infected cats reported changes in serum iron levels, alterations in the activity of enzymes of the cholinergic system, and oxidative stress correlated to normocytic, normochromic, and regenerative anemia. During this article, the aforementioned parameters will be simultaneously analyzed and related to hematological parameters that determine anemia in cats infected with this protozoan.

Seasonal alterations in serum iron levels in elite football players

It is very important to monitor levels of serum iron and other factors of iron metabolism and oxygen transport system as they play a very important role in functional ability of football players. A decrease in serum iron level can be the very first sign of development of iron deficiency anaemia, which seriously influences health and functional ability of an athlete and is a common problem in competitive sports. The aim of this study was to observe and evaluate changes in serum iron values during the competition season in relation to the training process. During four years, serum iron level was measured in 28-34 players of one of the top football clubs in Serbia, four times a year: at the beginning and at peak-point of both half-seasons. Differences between basic and control findings, relative and absolute changes in serum iron levels and statistical significance of the findings were than calculated. There was a significant decrease in mean serum iron levels on each control test, compared to basic values. Mean value of control serum iron levels is significantly lower than mean of preseason values (20.64 +/- 6.58 vs. 16.38 +/- 5.51 micromol/l). A significant decrease in serum iron level among footballers during both half-seasons is most probably due to an increased loss and/or diminished absorption resulting from a high intensity training process. Because the decline in serum iron may be an early sign of iron store depletion and iron deficiency anaemia, it is very important to evaluate it regularly, along with other factors of iron metabolism and oxygen transport system.

Evaluation of the changes in serum iron levels in pre-eclampsia

Serum iron levels were studied in 50 patients with pre-eclampsia and the results were compared with 50 control cases. Their serum iron levels were found to be higher than the controls. Increase in serum iron was directly proportional to the increased levels of uric acid, urea and creatinine. Mean reticulocyte counts, plasma free haemoglobin and unconjugated bilirubin levels were also higher in these patients. It is suggested that haemolysis may be a major contributory factor for the increased levels of serum iron in pre-eclampsia.

Significance of serum iron levels as a biochemical marker in pregnancy-induced hypertension

OBJECTIVE: To determine the changes in serum iron levels, if any, as a biochemical marker of pregnancy-induced hypertension (PIH). METHOD: Fifty-four primigravidas with PIH formed the study group and 20 normotensive primigravidas comprised the control group in a prospective study. Serum iron levels were estimated at diagnosis of PIH, at termination of pregnancy and in the postpartum period. Data was analyzed using Student's t-test, the X 2-test and regression analysis. RESULTS: Subjects with PIH were found to have higher serum iron levels at diagnosis of PIH (recruitment value) and at termination of pregnancy than the controls ( P < 0.001). Serum iron levels in the PIH subjects decreased markedly in the postpartum period simultaneously with the clinical recovery from PIH. Serum iron values of ≥ 110 gg/dl was found to differentiate PIH from normotensive pregnancies with a sensitivity and specificity of 89% and 90%, respectively. CONCLUSIONS: Changes in serum iron levels correlated with the clinical course of PIH and appeared to be a uniform and specific biochemical marker of PIH although its correlation with the severity of PIH was found to be poor.

Changes in serum iron levels following very high-dose cisplatin.

A four-fold (P less than 0.001) mean increase in iron levels was found in 18 patients (a total of 36 courses of therapy) with ovarian cancer at the end of a 5-day course of cisplatin (40 mg/m2 per day every 4-5 weeks). The kinetics of these modifications began very early (24-48 h after initiation of therapy): they reached their maximum on the 4th-5th day, coinciding with the last drug administration, and basal levels were recovered after the 10th day. A subsequent eight-fold average increase (P less than 0.001) in ferritin serum levels, beginning 2 days after the iron changes, was observed, but showed a slower regression (after the 15th day). Reticulocyte counts were lowered (P less than 0.001) with the same time-course of the iron increases, but returned to pretreatment levels within 2 weeks. Total bilirubin and serum glutamate-pyruvate transaminase showed significantly delayed increases compared with iron. The results are in keeping with a reduced iron utilization by the erythroid precursors, but other mechanisms cannot be excluded. There is no statistical correlation between the early iron increases and the subsequent hemoglobin nadir values.

Changes in serum iron levels due to infection with hepatitis B virus

We found in two previous studies (Down syndrome patients and end-stage kidney patients receiving renal dialysis) that total serum iron is higher on average in carriers of the hepatitis B virus than in those who are not. The elevation of the serum iron is independent of elevations of serum L-alanine:2-oxoglutarate aminotransferase, EC 2.6.1.2) (SGPT), an indicator of liver cell damage. We have followed for 10 yr a large number of patients with end-stage renal disease receiving renal dialysis. In this paper we describe studies of serum iron and SGPT levels in patients (i) 1 mo before infection, (ii) after infection but within the month of infection, and (iii) 6-12 mo after infection. Comparisons of serum iron levels were made between those infected who retained the virus (carriers) and those who rejected the infection (transients). There were no differences between these groups before infection. Serum iron remained high in the carrier group and dropped in the transients. However, not all of the carriers retained high levels, although this was the case in general. Individual changes in the pre- and postconversion period were then considered. All carriers who had a preconversion decline in iron had an increase after infection, whereas this occurred in only some of the transients. Those carriers who had a decline after infection had raised levels before infection, and the decline was generally less than the increase. Consideration of the SGPT and the iron levels together led to the same conclusion as the previous studies, that elevation of iron may be independent of rise in SGPT. Several hypotheses were derived from these findings. Individuals who are carriers in general have higher iron levels and, therefore, are more likely to become infected with bacteria; this may contribute to increased morbidity and mortality. From experimental evidence, iron is required for the growth of tumor cells. Carriers with elevated iron levels may be more likely to develop detectable cancer of the liver than those who do not.