Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology.

Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID-19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.

Retacrit®, Biosimilar of Epoetin Alfa, in Chemotherapy-Induced Anemia in Routine Practice: Impact of Iron Supplementation.

INTRODUCTION: The aim of the study was to evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alfa (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation. METHODS: This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievement of target Hb (with an increase of Hb ≥1 g/dL) or an increase of Hb ≥2 g/dL, in the absence of transfusion in the previous 3 weeks. RESULTS: 2,076 patients (women, 50.6%; mean age, 67.0 years) with malignant diseases (solid tumors, 79.8%; lymphomas, 12.7%; multiple myeloma, 6.6%) were analyzed. A total of 655 patients received oral iron (40.5%), intravenous iron (58.9%), or both (0.6%). At inclusion, 10.0% and 18.2% of patients without and with iron supplementation had serum ferritin <100 µg/L, respectively. Transferrin saturation (TSAT) ≤20% was more frequent in patients with supplementation (76.6%) than without supplementation (33.9%). The mean weekly doses of epoetin alfa biosimilar and planned duration of treatment were comparable regardless of iron supplementation. The primary endpoint was achieved in 70.5% and 70.2% of patients without and with iron supplementation, respectively. Three (0.1%) serious thromboembolic events related to treatment with epoetin alfa biosimilar were reported. CONCLUSION: Epoetin alfa biosimilar was effective and well tolerated for treating chemotherapy-induced anemia. Patients in subgroup with iron supplementation had lower TSAT at inclusion compared to subgroup without supplementation. Comparable mean Hb levels were achieved in both subgroups. The rate of patients with iron supplementation through the intravenous route was however insufficient.

Anti-EGFR Single-Chain Fv Antibody Fragment Displayed on the Surface of Ferritin H-Chain Protein Nanoparticle for Asthma Therapy.

Epidermal growth factor receptor (EGFR)-dependent signaling contributes to the pathophysiology of asthma. However, these findings have not been translated into a clinical application. We recently generated ferritin H-chain protein (FTH1)-based nanoparticles with an anti-EGFR single-chain Fv (anti-EGFR scFv) on the surface of FTH1, namely, anti-EGFR scFv-FTH1/FTH1 nanoparticles. In the present study, we found that these nanoparticles could specifically bind to EGFR-expressing cells, leading to downregulation of EGFR and mucin 5AC (MUC5AC) protein expression and growth suppression of House Dust Mite (HDM)-stimulated human bronchial epithelial 16HBE and lipopolysaccharides (LPS)-activated murine macrophage-like RAW264.7 cells. In vivo, intraperitoneal administration of anti-EGFR scFv-FTH1/FTH1 nanoparticles, but not FTH1 nanoparticles, alleviated the major pathological symptoms including airway hyperresponsiveness, airway inflammation, goblet cell hyperplasia, mucus hyperproduction, and increased release of Th2 cytokines in an allergen ovalbumin (OVA)-induced asthma mouse model. Importantly, during the dosing period these nanoparticles were safe for both heathy and asthmatic mice, and more effective in controlling airway inflammation than cetuximab, an EGFR monoclonal antibody. Altogether, our studies provide insights into the control of airway inflammation for treatment of asthma by targeting EGFR. The similar strategy can be used to fabricate scFv-based recombinant protein nanoparticles for other clinical applications.

Association between the ferritin level and risk of gestational diabetes mellitus: A meta-analysis of observational studies.

AIMS/INTRODUCTION: The relationship between ferritin and the risk of gestational diabetes mellitus (GDM) has not been established. Thus, we carried out a meta-analysis based on the current literature. MATERIALS AND METHODS: We searched relevant databases on Embase, PubMed, Cochrane Library and Web of Science before 10 May 2019 to determine the relationship between ferritin and the risk of GDM. The relative risks and 95% confidence intervals of GDM risk were summarized using a random effects model. Studies using categories of ferritin as exposure were combined by dose-response analysis. We carried out both linear and non-linear trends. We also carried out subgroup analysis, whether or not the studies adjusted for potential confounders, and meta-regression analysis to explore the source of heterogeneity. Sensitivity analysis was carried out to explore the robustness of the meta-analysis results. RESULTS: A total of 10 studies involving 4,690 participants were identified. The summary relative risk comparing persons with the highest concentration categories of ferritin with the lowest concentration categories of ferritin was 1.87 (95% confidence interval 1.50-2.34; I2  = 20.1%). Linear dose-response showed that an increase in ferritin of 10 µg/L increased the risk of GDM by 8% (1.08, 95% confidence interval 1.05-1.13, I2  = 55.1%; n = 4). A non-linear dose-response relationship also showed a consistently increasing risk of GDM with increased ferritin. No evidence of publication bias was detected. CONCLUSIONS: The findings from this meta-analysis suggest that increased ferritin levels are associated with an increased risk of GDM; however, we require further prospective cohort studies to confirm the results, especially the dose-response relationship between ferritin and GDM.

Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.

BACKGROUND: Anaemia is a condition in which the number of red blood cells is insufficient to meet physiologic needs; it is caused by many conditions, particularly iron deficiency. Traditionally, daily iron supplementation has been a standard practice for preventing and treating anaemia. However, its long-term use has been limited, as it has been associated with adverse side effects such as nausea, constipation, and teeth staining. Intermittent iron supplementation has been suggested as an effective and safer alternative to daily iron supplementation for preventing and reducing anaemia at the population level, especially in areas where this condition is highly prevalent. OBJECTIVES: To assess the effects of intermittent oral iron supplementation, alone or in combination with other nutrients, on anaemia and its associated impairments among menstruating women, compared with no intervention, a placebo, or daily supplementation. SEARCH METHODS: In February 2018, we searched CENTRAL, MEDLINE, Embase, nine other databases, and two trials registers. In March 2018, we also searched LILACS, IBECS and IMBIOMED. In addition, we examined reference lists, and contacted authors and known experts to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs with either individual or cluster randomisation. Participants were menstruating women; that is, women beyond menarche and prior to menopause who were not pregnant or lactating and did not have a known condition that impeded the presence of menstrual periods. The intervention was the use of iron supplements intermittently (one, two or three times a week on non-consecutive days) compared with placebo, no intervention, or the same supplements provided on a daily basis. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy, assessed the risk of bias of the included studies, and rated the quality of the evidence using GRADE. MAIN RESULTS: We included 25 studies involving 10,996 women. Study methods were not well described in many of the included studies and thus assessing risk of bias was difficult. The main limitations of the studies were lack of blinding and high attrition. Studies were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one third of the included studies did not provide a funding source.Although quality across studies was variable, the results consistently showed that intermittent iron supplementation (alone or with any other vitamins and minerals) compared with no intervention or a placebo, reduced the risk of having anaemia (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.49 to 0.87; 11 studies, 3135 participants; low-quality evidence), and improved the concentration of haemoglobin (mean difference (MD) 5.19 g/L, 95% CI 3.07 to 7.32; 15 studies, 2886 participants; moderate-quality evidence), and ferritin (MD 7.46 µg/L, 95% CI 5.02 to 9.90; 7 studies, 1067 participants; low-quality evidence). Intermittent regimens may also reduce the risk of having iron deficiency (RR 0.50, 95% CI 0.24 to 1.04; 3 studies, 624 participants; low-quality evidence), but evidence was inconclusive regarding iron deficiency anaemia (RR 0.07, 95% CI 0.00 to 1.16; 1 study, 97 participants; very low-quality evidence) and all-cause morbidity (RR 1.12, 95% CI 0.82 to 1.52; 1 study, 119 participants; very low-quality evidence). Women in the control group were less likely to have any adverse side effects than those receiving intermittent iron supplements (RR 1.98, 95% CI 0.31 to 12.72; 3 studies, 630 participants; moderate-quality evidence).In comparison with daily supplementation, results showed that intermittent supplementation (alone or with any other vitamins and minerals) produced similar effects to daily supplementation (alone or with any other vitamins and minerals) on anaemia (RR 1.09, 95% CI 0.93 to 1.29; 8 studies, 1749 participants; moderate-quality evidence). Intermittent supplementation may produce similar haemoglobin concentrations (MD 0.43 g/L, 95% CI -1.44 to 2.31; 10 studies, 2127 participants; low-quality evidence) but lower ferritin concentrations on average (MD -6.07 µg/L, 95% CI -10.66 to -1.48; 4 studies, 988 participants; low-quality evidence) compared to daily supplementation. Compared to daily regimens, intermittent regimens may also reduce the risk of having iron deficiency (RR 4.30, 95% CI 0.56 to 33.20; 1 study, 198 participants; very low-quality evidence). Women receiving iron supplements intermittently were less likely to have any adverse side effects than those receiving iron supplements daily (RR 0.41, 95% CI 0.21 to 0.82; 6 studies, 1166 participants; moderate-quality evidence). No studies reported on the effect of intermittent regimens versus daily regimens on iron deficiency anaemia and all-cause morbidity.Information on disease outcomes, adherence, economic productivity, and work performance was scarce, and evidence about the effects of intermittent supplementation on these outcomes unclear.Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria was frequent, although very few trials were conducted in these settings. AUTHORS' CONCLUSIONS: Intermittent iron supplementation may reduce anaemia and may improve iron stores among menstruating women in populations with different anaemia and malaria backgrounds. In comparison with daily supplementation, the provision of iron supplements intermittently is probably as effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression, and adherence to the intervention. The quality of this evidence base ranged from very low to moderate quality, suggesting that we are uncertain about these effects.

Risk factors for heart disease in transfusion-dependent thalassemia: serum ferritin revisited.

Heart disease remains a leading cause of morbidity and mortality in transfusion-dependent thalassemia (TDT), which can be attributed to several factors but primarily develops in the setting of iron overload. This was a retrospective cohort study utilizing Webthal® patient data from five major centers across Italy. Patients without heart disease were followed-up for 10 years (2000-2010) and data were collected for demographics, splenectomy status, serum ferritin and hemoglobin levels, and comorbidities associated with heart disease. Among 379 patients analyzed (mean age 22.9 ± 5.1 years, 47.8% men), 44 (cumulative incidence: 11.6%) developed heart disease during the period of observation. Splenectomy (p = 0.002) and serum ferritin level (p < 0.001) were the only risk factors with significant association with heart disease. A serum ferritin threshold of ≥ 3000 ng/mL was the best predictor for the development of heart disease (86.4% sensitivity and 92.8% specificity, AUC: 0.912, 95% CI 0.852-0.971, p < 0.001). On multivariate analysis, only a serum ferritin level ≥ 3000 ng/mL remained significantly and independently associated with increased risk of heart disease (HR: 44.85, 95% CI 18.85-106.74), with a 5- and 10-year heart disease-free survival of 58 and 39%. The association between iron overload and heart disease in patients with TDT is confirmed, yet a new serum ferritin level of 3000 ng/mL to flag increased risk is suggested.

Ferritinophagy/ferroptosis: Iron-related newcomers in human diseases.

Nuclear receptor coactivator 4 mediated ferritinophagy is an autophagic phenomenon that specifically involves ferritin to release intracellular free iron. Ferritinophagy is implicated in maintaining efficient erythropoiesis. Notably, ferritinophagy also plays a central role in driving some pathological processes, including Parkinson's disease (PD) and urinary tract infections. Some evidence has demonstrated that ferritinophagy is critical to induce ferroptosis. Ferroptosis is a newly nonapoptotic form of cell death, characterized by the accumulation of iron-based lipid reactive oxygen species. Ferroptosis plays an important role in inhibiting some types of cancers, such as hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, and breast cancer. Conversely, the activation of ferroptosis accelerates neurodegeneration diseases, including PD and Alzheimer's disease. Therefore, in this review, we summarize the regulatory mechanisms related to ferritinophagy and ferroptosis. Moreover, the distinctive effects of ferritinophagy in human erythropoiesis and some pathologies, coupled with the promotive or inhibitory role of tumorous and neurodegenerative diseases mediated by ferroptosis, are elucidated. Obviously, activating or inhibiting ferroptosis could be exploited to achieve desirable therapeutic effects on diverse cancers and neurodegeneration diseases. Interrupting ferritinophagy to control iron level might provide a potentially therapeutic avenue to suppress urinary tract infections.

Role of liver magnetic resonance imaging in hyperferritinaemia and the diagnosis of iron overload.

Hyperferritinaemia is a frequent clinical problem. Elevated serum ferritin levels can be detected in different genetic and acquired diseases and can occur with or without anaemia. It is therefore important to determine whether hyperferritinaemia is due to iron overload or due to a secondary cause. The main causes of iron overload are intestinal iron hyperabsorption disorders and transfusion-dependent disorders. Iron homeostasis and iron overload are quantified by different diagnostic approaches. The evaluation of serum ferritin and transferrin saturation is the first diagnostic step to identify the cause of hyperferritinaemia. The assessment of liver iron concentration by liver biopsy or magnetic resonance imaging (MRI) may guide the further diagnostic and therapeutic workup. Liver biopsy is invasive and poorly accepted by patients and should only be carried out in selected patients with hereditary haemochromatosis. As a non-invasive approach, MRI is considered the standard method to diagnose and to monitor both hepatic iron overload and the effectiveness of iron chelation therapy in many clinical conditions such as thalassaemia and myelodysplastic syndromes. Accurate evaluation and monitoring of iron overload has major implications regarding adherence, quality of life and prognosis. There are different technical MRI approaches to measuring the liver iron content. Of these, T2 and T2* relaxometry are considered the standard of care. MRI with cardiac T2* mapping is also suitable for the assessment of cardiac iron. Currently there is no consensus which technique should be preferred. The choice depends on local availability and patient population. However, it is important to use the same MRI technique in subsequent visits in the same patient to get comparable results. Signal intensity ratio may be a good adjunct to R2 and R2* methods as it allows easy visual estimation of the liver iron concentration. In this review a group of Swiss haematologists and radiologists give an overview of different conditions leading to primary or secondary iron overload and on diagnostic methods to assess hyperferritinaemia with a focus on the role of liver MRI. They summarise the standard practice in Switzerland on the use of liver iron concentration MRI as well as disease-specific guideline recommendations.

High Ferritin Level and Malnutrition Predict High Risk of Infection-Related Hospitalization in Incident Dialysis Patients: A Japanese Prospective Cohort Study.

AIMS: The aim of the study was to clarify the relationship between serum ferritin and infectious risks. METHODS: We evaluated all hospital admissions due to infections, clinical biomarkers and nutrition status in 129 incident Japanese dialysis patients during a median follow-up of 38 months. RESULTS: Kaplan-Meier analysis revealed that the period without infections requiring hospitalization was significantly shorter in ferritin > median (82.0 ng/ml) group than in the ferritin < median group (log-rank test 4.44, p = 0.035). High ferritin was associated with significantly increased relative risk of hospitalization for infection (Cox hazard model 1.52, 95% CI 1.06-2.17). The number of hospitalization days was gradually longer in patients with high ferritin levels and malnutrition. CONCLUSION: Although serum ferritin levels were low, and doses of iron administered to dialysis patients in Japan are generally lower than in Western countries, an elevated ferritin level was associated with increased risk of infection, particularly in patients with poor nutritional status.

Evaluation of Safety of Iron-Fortified Soybean Sprouts, a Potential Component of Functional Food, in Rat.

Ferritin-iron is currently considered as one of the most promising iron forms to prevent iron deficiency anaemia. We found that the cultivation of soybean seeds in a solution of ferrous sulfate results in material with extremely high iron content - 560.6 mg Fe/100 g of dry matter, while ferritin iron content was 420.5 mg/100 g dry matter. To assess the potential adverse effects of a preparation containing such a high concentration of iron, male and female Wistar rats were exposed via diet to 10, 30, 60 g soybean sprouts powder/kg feed for 90 days. There were no differences in final body weight and mean food consumption between controls and rats administered sprouts. No statistically significant differences in haematology and clinical chemistry parameters were found between controls and treated rats. Microscopic examination of 22 tissues did not reveal any pathology due to soybean sprouts intake. Long term administration of the test material did not cause oxidative damage to DNA and protein in the liver as evidenced by the unchanged basal levels of DNA damage as well as carbonyl groups content. Lipid peroxidation was slightly increased only in females. The activity of several antioxidant enzymes: superoxide dismutase, glutathione peroxidase and glutathione S-transferase was increased, which substantially enhanced the antioxidant status in the liver from the rats treated with soybean sprouts. Hence, the material tested can be recommended as a component of food supplements for individuals with iron deficiency anaemia and inflammatory bowel diseases.

Prevalence of iron overload complications among patients with b-thalassemia major treated at Dubai Thalassemia Centre.

BACKGROUND AND OBJECTIVES: Authors and team members of the Dubai Thalassemia Centre obtained data on the prevalence of iron overload complications among patients with b-thalassemia major (b-TM) and compared it to international data to improve patient care and evaluate the effectiveness of earlier used treatment modalities. The information obtained is also expected to be useful in genetic counseling. DESIGN AND SETTING: Cross-sectional study of all living transfusion-dependent b-TM patients registered at the Thalassemia Centre in Dubai, United Arab Emirates, until the end of 2007 (n=382). PATIENTS AND METHODS: Diagnosis of TM was based on clinical history and laboratory confirmation by hemoglobin electrophoresis and DNA testing. All were uniformly treated with desferrioxamine and monitored by serial serum ferritin. results: The mean (SD) age of patients was 15.4 (7.6) years, with 50.5% males. Mean (SD) serum ferritin was 2597.2 (1976.8) micro g/L. The frequency of iron overload complications were as follows: hypogonadism (n=99, 52.7%), hypoparathyroidism (n=40, 10.5%), diabetes mellitus (n=40, 10.5%), hypothyroidism (n=24, 6.5%) and cardiomyopathies (n=7, 1.8%). Hypogonadism was the most common endocrine abnormality in our study and other reported series. However, cardiomyopathies were less prevalent among our patients with higher rates of diabetes and hypoparathyroidism compared to rates reported internationally. Females had statistically significant lower serum ferritin (2530.8 (1931.2), P < .05) with a lower cardiomyopathies rate. CONCLUSION: Iron overload related complications among our patients with thalassemia major were different from those reported internationally. Studying the genetic status of patients from our area may uncover the underlying genetic modifiers of iron overload mediated organs injury.

A prospective study of intakes of zinc and heme iron and colorectal cancer risk in men and women.

Although laboratory studies linked zinc and heme iron to colorectal cancer, epidemiologic evidence is limited. We prospectively examined these associations in the Nurses' Health Study and Health Professionals Follow-up Study. We used Cox proportional hazards regression analyses to calculate cohort-specific relative risks (RRs) and pooled results using a fixed-effects model. We documented 2,114 incident colorectal cancer cases during up to 22 years of follow-up. Compared highest to lowest quintile of dietary zinc intake, the pooled multivariable RRs (95% CIs) were 0.86 (0.73, 1.02) for colorectal cancer, 0.92 (0.76, 1.11) for colon cancer, and 0.68 (0.47, 0.99) for rectal cancer. The significant inverse association between dietary zinc intake and risk of rectal cancer was mainly driven by data in women, although the difference in the sex-specific results was not statistically significant. For the same comparison, the pooled multivariable RRs (95% CIs) for heme iron were 1.10 (0.93, 1.30) for colorectal cancer, 1.06 (0.88, 1.29) for colon cancer, and 1.20 (0.83, 1.75) for rectal cancer. These associations were not significantly modified by alcohol consumption, body mass index, physical activity, menopausal status, or postmenopausal hormone use. Total zinc intake, total iron intake, dietary iron intake, and zinc or iron supplement uses were largely not associated with colorectal cancer risk. Our study does not support strong roles of zinc and heme iron intake in colorectal cancer risk; however, a suggestive inverse association of dietary zinc intake with rectal cancer risk in women requires further study.

Very high serum ferritin levels are associated with increased mortality and critical care in pediatric patients.

OBJECTIVE: To determine whether an elevated serum ferritin level is independently associated with mortality and receipt of critical care in pediatric patients. DESIGN: Retrospective cohort study, open population. SETTING: Seattle Children's Hospital, Seattle, WA, from September 2, 2003, to February 15, 2008. PATIENTS: All patients tested for serum ferritin level from September 2, 2003, to August 16, 2007, with a level ≥1000 ng/mL. INTERVENTIONS: None. MAIN ANALYSIS: Cox regression. MEASUREMENTS AND MAIN RESULTS: The predictor of interest was the patient-specific peak serum ferritin level, dichotomized a priori at 3000 ng/mL. The outcomes were mortality and intensive care unit admission. A total of 171 patients met the inclusion criteria. The observation time without death or intensive care unit admission ranged from 184 to 1621 days. The hazard ratio of death with peak ferritin of >3000 ng/mL was 4.32 (95% confidence interval 2.21-8.47, p < .001) compared to peak ferritin of 1000-3000 ng/mL. The hazard ratio of intensive care unit admission with peak ferritin of >3000 ng/mL was 2.49 (95% confidence interval 1.53-4.05, p < .001) compared to peak ferritin of 1000-3000 ng/mL. Both estimates were adjusted for bone marrow transplant, solid organ transplant, hemoglobinopathy, and existing rheumatologic disease. CONCLUSION: In this pediatric population, with serum ferritin levels of >3000 ng/mL, there was increased risk for both receipt of critical care and subsequent death.

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial).

BACKGROUND: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet). METHODS: Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp(R), Amgen) for >or= 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events). DISCUSSION: This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

Electrochemical detection of natural DNA damage induced by ferritin/ascorbic acid/H2O2 system and amplification of DNA damage by endonuclease Fpg.

Oppositely charged natural DNA and chitosan (CS) were assembled into (CS/DNA)(n) layer-by-layer films on electrode surface, and Ru(bpy)(3)(2+) (bpy = bipyridyl) in solution was used as electroactive catalyst to detect damage of DNA in the films after incubation of the films in ferritin/AA/H(2)O(2) solutions (AA = ascorbic acid). The mechanism of DNA damage caused by the ferritin/AA/H(2)O(2) system was similar to that of Fenton reaction, where the reaction of ferritin with AA would release some Fe(II) ions from ferritin and the following reaction between Fe(II) ions and H(2)O(2) would produce hydroxyl radical, which could induce DNA oxidative damage. This system provided an in vitro model to imitate the DNA damage indirectly induced by ferritin in real bio-systems. In addition, formamidopyrimidine DNA glycosylase (Fpg), a key endonuclease enzyme in repair of oxidatively damaged DNA, was used to amplify the DNA damage caused by ferritin/AA/H(2)O(2) system through conversion of oxidative purine bases into single-strand breaks. The high sensitivity of electrocatalytic method with Ru(bpy)(3)(2+) as the catalyst in detection of DNA damage and the magnification function of Fpg may provide a novel idea to detect natural DNA lesion sensitively.