Iron sequestration by transferrin 1 mediates nutritional immunity in Drosophila melanogaster.

Iron sequestration is a recognized innate immune mechanism against invading pathogens mediated by iron-binding proteins called transferrins. Despite many studies on antimicrobial activity of transferrins in vitro, their specific in vivo functions are poorly understood. Here we use Drosophila melanogaster as an in vivo model to investigate the role of transferrins in host defense. We find that systemic infections with a variety of pathogens trigger a hypoferremic response in flies, namely, iron withdrawal from the hemolymph and accumulation in the fat body. Notably, this hypoferremia to infection requires Drosophila nuclear factor κB (NF-κB) immune pathways, Toll and Imd, revealing that these pathways also mediate nutritional immunity in flies. Next, we show that the iron transporter Tsf1 is induced by infections downstream of the Toll and Imd pathways and is necessary for iron relocation from the hemolymph to the fat body. Consistent with elevated iron levels in the hemolymph, Tsf1 mutants exhibited increased susceptibility to Pseudomonas bacteria and Mucorales fungi, which could be rescued by chemical chelation of iron. Furthermore, using siderophore-deficient Pseudomonas aeruginosa, we discover that the siderophore pyoverdine is necessary for pathogenesis in wild-type flies, but it becomes dispensable in Tsf1 mutants due to excessive iron present in the hemolymph of these flies. As such, our study reveals that, similar to mammals, Drosophila uses iron limitation as an immune defense mechanism mediated by conserved iron-transporting proteins transferrins. Our in vivo work, together with accumulating in vitro studies, supports the immune role of insect transferrins against infections via an iron withholding strategy.

Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1.

Ferroptosis is an iron-dependent programmed cell death event, whose regulation and physiological significance remain to be elucidated. Analyzing transcriptional responses of mouse embryonic fibroblasts exposed to the ferroptosis inducer erastin, here we found that a set of genes related to oxidative stress protection is induced upon ferroptosis. We considered that up-regulation of these genes attenuates ferroptosis induction and found that the transcription factor BTB domain and CNC homolog 1 (BACH1), a regulator in heme and iron metabolism, promotes ferroptosis by repressing the transcription of a subset of the erastin-induced protective genes. We noted that these genes are involved in the synthesis of GSH or metabolism of intracellular labile iron and include glutamate-cysteine ligase modifier subunit (Gclm), solute carrier family 7 member 11 (Slc7a11), ferritin heavy chain 1 (Fth1), ferritin light chain 1 (Ftl1), and solute carrier family 40 member 1 (Slc40a1). Ferroptosis has also been previously shown to induce cardiomyopathy, and here we observed that Bach1-/- mice are more resistant to myocardial infarction than WT mice and that the severity of ischemic injury is decreased by the iron-chelator deferasirox, which suppressed ferroptosis. Our findings suggest that BACH1 represses genes that combat labile iron-induced oxidative stress, and ferroptosis is stimulated at the transcriptional level by BACH1 upon disruption of the balance between the transcriptional induction of protective genes and accumulation of iron-mediated damage. We propose that BACH1 controls the threshold of ferroptosis induction and may represent a therapeutic target for alleviating ferroptosis-related diseases, including myocardial infarction.

IL-17C Protects Nasal Epithelium from Pseudomonas aeruginosa Infection.

IL-17 family cytokines are directly involved in host immune responses and the critical mediators for host defense against infection or inflammation. IL-17C is highly expressed in respiratory epithelium and is induced after acute bacterial lung infection. However, the definite function of IL-17C induced by Pseudomonas aeruginosa (PAO1 strain) is not fully understood, and our study was designed to demonstrate IL-17C-induced immune response against PAO1 infection in nasal epithelium. Passage-2 normal human nasal epithelial (NHNE) cells were infected with PAO1 and the relationship between IL-17C-related immune responses and the iron absorption of PAO1, depending on inoculation of recombinant human IL-17C (rhIL-17C), was assessed by measuring the siderophore activity of PAO1. Microarray data showed that IL-17C expression increased 34.7 times at 8 hours postinfection (hpi) in NHNE cells, and IL-17C mRNA levels increased until 48 hpi. The PAO1 colonies significantly increased from 8 hpi in NHNE cells, and siderophore activity of PAO1 was enhanced in the supernatants of PAO1-infected NHNE cells. Interestingly, PAO1 colonies were reduced in PAO1-infected NHNE cells treated with rhIL-17C, and supernatants from NHNE cells treated with rhIL-17C also exhibited decreased PAO1 colonies. We found that the siderophore activity of PAO1 was significantly reduced in the supernatants of NHNE cells treated with rhIL-17C where LCN2 expression was highly elevated. Our findings indicate that IL-17C mediates an antibacterial effect against PAO1 by inhibiting siderophore activity in nasal epithelium. We propose that IL-17C might be an efficient mediator to suppress PAO1 infection through disturbing iron absorption of PAO1 in nasal epithelium.

Iron Sequestrant DIBI, a Potential Alternative for Nares Decolonization of Methicillin-Resistant Staphylococcus aureus, Is Anti-infective and Inhibitory for Mupirocin-Resistant Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) opportunistic infections are a major health burden. Decolonization of hospitalized patients with mupirocin (MUP) has reduced the incidence of infection but has led to MUP resistance. DIBI is a developmental-stage anti-infective agent that sequesters bacterial iron and bolsters innate host iron-withdrawal defenses. Clinical isolates possessing low, high, or no MUP resistance all had similarly high susceptibilities to DIBI. Intranasal DIBI reduced nares bacterial burdens in mice to the same extent as MUP. No resistance was found after exposure to DIBI.

Antibiotic-Resistant Acinetobacter baumannii Is Susceptible to the Novel Iron-Sequestering Anti-infective DIBI In Vitro and in Experimental Pneumonia in Mice.

Acinetobacter baumannii is a major cause of nosocomial infections especially hospital-acquired pneumonia. This bacterium readily acquires antibiotic resistance traits and therefore, new treatment alternatives are urgently needed. The virulence of A. baumannii linked to iron acquisition suggests a potential for new anti-infectives that target its iron acquisition. DIBI, a 3-hydroxypyridin-4-one chelator, is a purpose-designed, iron-sequestering antimicrobial that has shown promise for treating microbial infection. DIBI was investigated for its in vitro and in vivo activities against clinical A. baumannii isolates. DIBI was inhibitory for all isolates tested with very low MICs (2 µg/ml, equivalent to 0.2 µM), i.e., at or below the typical antibiotic MICs reported for antibiotic-sensitive strains. DIBI inhibition is Fe specific, and it caused an iron-restricted bacterial physiology that led to enhanced antibiotic killing by several discrete antibiotics. DIBI also strongly suppressed recovery growth of the surviving population following antibiotic exposure. A low intranasal dose (11 µmol/kg) of DIBI after intranasal challenge with hypervirulent ciprofloxacin (CIP)-resistant A. baumannii LAC-4 significantly reduced bacterial burdens in mice, and DIBI also suppressed the spread of the infection to the spleen. Treatment of infected mice with CIP alone (20 mg/kg, equivalent to 60 µmol/kg) was ineffective given LAC-4's CIP resistance, but if combined with DIBI, the treatment efficacy improved significantly. Our evidence suggests that DIBI restricts host iron availability to A. baumannii growing in the respiratory tract, bolstering the host innate iron restriction mechanisms. DIBI has potential as a sole anti-infective or in combination with conventional antibiotics for the treatment of A. baumannii pneumonia.

Mini-Review: Oxidative stress, redox stress or redox success?

The first life forms evolved in a highly reducing environment. This reduced state is still carried by cells today, which makes the concept of "reductive stress" somewhat redundant. When oxygen became abundant on the Earth, due to the evolution of photosynthesis, life forms had to adapt or become extinct. Living organisms did adapt, proliferated and an explosion of new life forms resulted, using reactive oxygen species (ROS) to drive their evolution. Adaptation to oxygen and its reduction intermediates necessitated the simultaneous evolution of select antioxidant defences, carefully regulated to allow ROS to perform their major roles. Clearly this "oxidative stress" did not cause a major problem to the evolution of complex life forms. Why not? Iron and oxygen share a close relationship in aerobic evolution. Iron is used in proteins to transport oxygen, promote electron transfers, and catalyse chemical reactions. In all of these functions, iron is carefully sequestered within proteins and restricted from reacting with ROS, this sequestration being one of our major antioxidant defences. Iron was abundant to life forms before the appearance of oxygen. However, oxygen caused its oxidative precipitation from solution and thereby decreased its bioavailability and thus the risk of iron-dependent oxidative damage. Micro-organisms had to adapt and develop strategies involving siderophores to acquire iron from the environment and eventually their host. This battle for iron between bacteria and animal hosts continues today, and is a much greater daily threat to our survival than "oxidative stress" and "redox stress".

Pre-operative haemoglobin levels and iron status in a large multicentre cohort of patients undergoing major elective surgery.

Pre-operative anaemia in patients undergoing major surgical procedures has been linked to poor outcomes. Therefore, early detection and treatment of pre-operative anaemia is recommended. However, to effectively implement a pre-operative anaemia management protocol, an estimation of its prevalence and main causes is needed. We analysed data from 3342 patients (44.5% female) scheduled for either: elective orthopaedic surgery (n = 1286); cardiac surgery (n = 691); colorectal cancer resection (n = 735); radical prostatectomy (n = 362); gynaecological surgery (n = 203) or resection of liver metastases (n = 122). For both sexes, anaemia was defined by a haemoglobin level < 130 g.l-1 ; absolute iron deficiency by ferritin < 30 ng.ml-1 (< 100 ng.ml-1 , if transferrin saturation < 20% or C-reactive protein > 5 mg.l-1 ); iron sequestration by transferrin saturation < 20% and ferritin > 100 ng.ml-1 ; and low iron stores by transferrin saturation > 20% and ferritin 30-100 ng.ml-1 . The overall prevalence of anaemia was 36%, with differences according to the type of surgery. Laboratory parameters allowing classification of iron status were available for 2884 patients. Among those with anaemia (n = 986), 677 (69%) were women, 608 (62%) presented with absolute iron deficiency, 101 (10%) with iron sequestration; and 150 (5%) with low iron stores. Iron status alterations were similar in women with haemoglobin < 130 g.l-1 or < 120 g.l-1 . For those who were not anaemic (n = 1898), corresponding figures were 656 (35%), 621 (33%), 165 (9%) and 518 (27%), respectively. Anaemia was present in one-third of patients undergoing major elective procedures. Over two-thirds of anaemic patients presented with absolute iron deficiency or iron sequestration. Over half of non-anaemic patients presented with absolute iron deficiency or low iron stores. We consider these data useful for planning pre-operative management of patients scheduled for major elective surgery.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

Mean corpuscular hemoglobin concentration: an anemia parameter predicting cardiovascular disease in incident dialysis patients.

BACKGROUND: Hemoglobin levels usually decline before dialysis initiation. The influence of overhydration on anemia progression and iron sequestration is poorly documented. Furthermore, clinical implications of anemia at dialysis initiation remain to be elucidated. METHODS: This multicenter retrospective cohort study enrolled incident dialysis patients. The patients were stratified by tertiles of overhydration rate (OH-R) defined by (BW - DW)/DW*100 (BW: body weight just before dialysis initiation, DW: dry weight). Time courses (6 months before, to 1 month after, dialysis initiation) of hemoglobin, C-reactive protein (CRP), and iron sequestration index (ISI) were examined using mixed effects models. We used Cox models to identify anemia parameters predicting subsequent cardiovascular disease (CVD). RESULTS: Among the 905 enrolled patients, hemoglobin levels gradually decreased before dialysis initiation and rapidly increased thereafter. An inverse V-shaped time course was observed for CRP and ISI with an increase during dialysis initiation. Patients with a higher OH-R showed lower hemoglobin levels along with higher CRP and ISI levels before dialysis initiation. Mean corpuscular hemoglobin concentration (MCHC) was more stable before dialysis initiation than were mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Low MCHC (< 32 g/dL) was independently associated with the incidence of nonatherosclerotic CVD. Patients with low MCHC tended to have increased left ventricular wall thickness and left atrial diameter. CONCLUSIONS: Progression of anemia before dialysis among overhydrated patients may mainly occur through hemodilution and iron sequestration partly induced by inflammation. Low MCHC reflects left atrial overload and left ventricular hypertrophy and hence may predict nonatherosclerotic CVD.

Interleukin-6 triggers toxic neuronal iron sequestration in response to pathological α-synuclein.

α-synuclein (α-syn) aggregation and accumulation drive neurodegeneration in Parkinson's disease (PD). The substantia nigra of patients with PD contains excess iron, yet the underlying mechanism accounting for this iron accumulation is unclear. Here, we show that misfolded α-syn activates microglia, which release interleukin 6 (IL-6). IL-6, via its trans-signaling pathway, induces changes in the neuronal iron transcriptome that promote ferrous iron uptake and decrease cellular iron export via a pathway we term the cellular iron sequestration response, or CISR. The brains of patients with PD exhibit molecular signatures of the IL-6-mediated CISR. Genetic deletion of IL-6, or treatment with the iron chelator deferiprone, reduces pathological α-syn toxicity in a mouse model of sporadic PD. These data suggest that IL-6-induced CISR leads to toxic neuronal iron accumulation, contributing to synuclein-induced neurodegeneration.

The iron transporter Transferrin 1 mediates homeostasis of the endosymbiotic relationship between Drosophila melanogaster and Spiroplasma poulsonii.

Iron is involved in numerous biological processes in both prokaryotes and eukaryotes and is therefore subject to a tug-of-war between host and microbes upon pathogenic infections. In the fruit fly Drosophila melanogaster, the iron transporter Transferrin 1 (Tsf1) mediates iron relocation from the hemolymph to the fat body upon infection as part of the nutritional immune response. The sequestration of iron in the fat body renders it less available for pathogens, hence limiting their proliferation and enhancing the host ability to fight the infection. Here we investigate the interaction between host iron homeostasis and Spiroplasma poulsonii, a facultative, vertically transmitted, endosymbiont of Drosophila. This low-pathogenicity bacterium is devoid of cell wall and is able to thrive in the host hemolymph without triggering pathogen-responsive canonical immune pathways. However, hemolymph proteomics revealed an enrichment of Tsf1 in infected flies. We find that S. poulsonii induces tsf1 expression and triggers an iron sequestration response similarly to pathogenic bacteria. We next demonstrate that free iron cannot be used by Spiroplasma while Tsf1-bound iron promotes bacterial growth, underlining the adaptation of Spiroplasma to the intra-host lifestyle where iron is mostly protein-bound. Our results show that Tsf1 is used both by the fly to sequester iron and by Spiroplasma to forage host iron, making it a central protein in endosymbiotic homeostasis.

Gene Expression Analysis Reveals the Concurrent Activation of Proapoptotic and Antioxidant-Defensive Mechanisms in Flavokawain B-Treated Cervical Cancer HeLa Cells.

Flavokawain B (FKB) is known to possess promising anticancer abilities. This is demonstrated in various cancer cell lines including HeLa cells. Cervical cancer is among the most widely diagnosed cancer among women today. Though FKB has been shown to be effective in treating cancer cells, the exact molecular mechanism is still unknown. This study is aimed at understanding the effects of FKB on HeLa cells using a microarray-based mRNA expression profiling and proteome profiling of stress-related proteins. The results of this study suggest that FKB induced cell death through p21-mediated cell cycle arrest and activation of p38. However, concurrent activation of antioxidant-related pathways and iron sequestration pathway followed by activation of ER-resident stress proteins clearly indicate that FKB failed to induce apoptosis in HeLa cells via oxidative stress. This effect implies that the protection of HeLa cells by FKB from H2O2-induced cell death is via neutralization of reactive oxygen species.

Lipocalin 2 regulates intestine bacterial survival by interplaying with siderophore in a weaned piglet model of Escherichia coli infection.

Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli (E. coli). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism. In this study, we showed that iron was sequestrated within cells in a piglet model of E. coli K88 infection. Siderophores was produced following E. coli K88 infection and siderophore-related genes expression was upregulated in iron-deficiency environment in vitro. Meanwhile, we found that Lcn2 expression was rapidly and robustly induced in jejunum by E. coli K88 infection and could be stimulated by IL-17 and IL-22. Furthermore, both Lcn2 induced in epithelial cells IPEC-1 and added exogenously as a recombinant protein could inhibit the growth of E. coli. We can conclude that Lcn2 is a crucial component of mucosal immune defense against intestinal infection with E. coli K88.

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies.IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis, causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis, which can be exploited for the design of new antitubercular therapies.

High Iron-Sequestrating Bifidobacteria Inhibit Enteropathogen Growth and Adhesion to Intestinal Epithelial Cells In vitro.

The gut microbiota plays an important role in host health, in particular by its barrier effect and competition with exogenous pathogenic bacteria. In the present study, the competition of Bifidobacterium pseudolongum PV8-2 (Bp PV8-2) and Bifidobacterium kashiwanohense PV20-2 (Bk PV20-2), isolated from anemic infant gut microbiota and selected for their high iron sequestration properties, was investigated against Salmonella Typhimurium (S. Typhi) and Escherichia coli O157:H45 (EHEC) by using co-culture tests and assays with intestinal cell lines. Single and co-cultures were carried out anaerobically in chemically semi-defined low iron (1.5 µM Fe) medium (CSDLIM) without and with added ferrous iron (30 µM Fe). Surface properties of the tested strains were measured by bacterial adhesion to solvent xylene, chloroform, ethyl acetate, and to extracellular matrix molecules, mucus II, collagen I, fibrinogen, fibronectin. HT29-MTX mucus-secreting intestinal cell cultures were used to study bifidobacteria competition, inhibition and displacement of the enteropathogens. During co-cultures in CSDLIM we observed strain-dependent inhibition of bifidobacterial strains on enteropathogens, independent of pH, organic acid production and supplemented iron. Bp PV8-2 significantly (P < 0.05) inhibited S. Typhi N15 and EHEC after 24 h compared to single culture growth. In contrast Bk PV20-2 showed less inhibition on S. Typhi N15 than Bp PV8-2, and no inhibition on EHEC. Affinity for intestinal cell surface glycoproteins was strain-specific, with high affinity of Bp PV8-2 for mucin and Bk PV20-2 for fibronectin. Bk PV20-2 showed high adhesion potential (15.6 ± 6.0%) to HT29-MTX cell layer compared to Bp PV8-2 (1.4 ± 0.4%). In competition, inhibition and displacement tests, Bp PV8-2 significantly (P < 0.05) reduced S. Typhi N15 and EHEC adhesion, while Bk PV20-2 was only active on S. Typhi N15 adhesion. To conclude, bifidobacterial strains selected for their high iron binding properties inhibited S. Typhi N15 and EHEC in co-culture experiments and efficiently competed with the enteropathogens on mucus-producing HT29-MTX cell lines. Further studies in complex gut ecosystems should explore host protection effects of Bp PV8-2 and Bk PV20-2 mediated by nutritional immunity mechanism associated with iron-binding.

Retrospective study of reticulocyte indices as indicators of iron-restricted erythropoiesis in dogs with immune-mediated hemolytic anemia.

Iron-restricted erythropoiesis can occur as a result of an absolute deficiency of iron stores, inflammation-mediated iron sequestration, or functional iron deficiency (in which release of stored iron is slower than the iron uptake by erythroid precursors during intense erythropoiesis). Reticulocyte indices are used to identify iron-restricted erythropoiesis, with the reticulocyte hemoglobin content (CHr) being the most commonly used index in human patients. Dogs with immune-mediated hemolytic anemia (IMHA) may have iron-restricted erythropoiesis caused by inflammation-mediated iron sequestration and/or functional iron deficiency, which could contribute to anemia severity and blunt the regenerative response in some dogs. To investigate this possibility, reticulocyte indices were examined retrospectively in 14 dogs (2-15 years of age; 9 spayed females, 1 intact female, 4 neutered males) with IMHA, and no clinical evidence of blood loss was found to suggest absolute iron deficiency. Five dogs (34%) had CHr below the preestablished lower reference limit (24.5 pg), and hematocrit was significantly lower in these dogs (p = 0.042, nonpaired t-test). Our results suggest that some dogs with IMHA may have iron-restricted erythropoiesis as a result of functional iron deficiency, inflammation-mediated iron sequestration, or (less likely) absolute iron deficiency. Further study is warranted to evaluate if dogs with IMHA may benefit from parenteral iron therapy.

Markers of iron metabolism in retired racing Greyhounds with and without osteosarcoma.

BACKGROUND: Greyhounds have well-described clinicopathologic idiosyncrasies, including a high prevalence of osteosarcoma (OSA). Hematocrit, HGB, and HGB oxygen affinity are higher than in other dogs, while haptoglobin concentration is lower, so we hypothesized that Greyhounds have a different iron metabolism. To our knowledge, there are no reports on serum iron profiles in Greyhounds. OBJECTIVES: To elucidate iron metabolism in Greyhounds, we wanted to compare serum iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (%SAT) in healthy retired racing Greyhounds (RRGs) with OSA (RRGs - OSA), and also with non-Greyhounds (NGs), without and with OSA (NGs - OSA). METHODS: Serum iron concentration and unsaturated iron-binding capacity (UIBC) were measured by standard methods, and TIBC and %SAT were calculated in RRGs (n = 25), RRGs - OSA (n = 28), NGs (n = 30), and NGs - OSA (n = 32). RESULTS: TIBC was lower in RRGs than in NGs (P < .0001), and in RRGs - OSA than in NGs - OSA (P < .0001). NGs - OSA had lower TIBC than healthy NGs (P = .003). Percent SAT was higher in RRGs than in NGs (P < .0001) and in RRGs - OSA (P = .008), and %SAT was also lower in NGs than in NGs - OSA (P = .004). Percent SAT was also higher in RRGs - OSA than in NGs - OSA (P = .001). Both RRGs - OSA (P = .02) and NGs - OSA (P < .0001) had lower serum iron concentrations than their healthy counterparts. CONCLUSION: Lower TIBC and higher %SAT may constitute another Greyhound idiosyncrasy compared with other dogs. In this study, all dogs with OSA had higher serum iron concentrations and %SAT than healthy dogs.

Hemoglobina reticulocitaria: un nuevo parámetro del hemograma de gran valor en el diagnóstico y manejo de la eritropoyesis deficiente en hierro / Reticulocyte hemoglobin: a new complete blood count (CBC) parameter valuable in the diagnosis and management of iron-deficient erythropoiesis

Resumen: la incorporación de los autoanalizador de hematología al laboratorio clínico no solo mejoró la calidad de los resultados de los parámetros convencionales del hemograma sino que ha permitido,especialmente con aquellos de última generación, introducir nuevos parámetros de gran utilidad clínica. Uno de los nuevos parámetros es la hemoglobina reticulocitaria, la cual se vislumbra como una potente herramienta en el diagnóstico y el manejo de la eritropoyesis deficiente en hierro en sus diferentes manifestaciones, en particular la deficiencia absoluta de hierro, la deficiencia funcional de hierro y el secuestro del hierro. La hemoglobina reticulocitaria en todos los casos en donde hay eritropoyesis deficiente en hierro es el primer parámetro detectable en el hemograma y, a su vez, es el primero que se normaliza cuando la terapia administrada ha sido la adecuada; además, ha demostradoser costo eficiente, sobre todo por ser un parámetro del hemograma más que una prueba adicional. El único problema, hasta el momento, es que solo está disponible en algunos autoanalizadoresde hematología como los de las compañías Siemens y Sysmex, en sus modelos de cuarta generación, también conocidos como hemograma tipo VI o hemograma ampliado o extendido. Con el presente módulo se pretende presentar este nuevo parámetro que la comunidad médica debe incorporar como propio y los laboratorios clínicos deberían estar preparados para incorporarlo a sus portafolios de servicios, como una nueva herramienta complementaria en la prevención, la detección y el manejo de la eritropoyesis deficiente en hierro en sus diversas manifestaciones.

Abstract: the incorporation of hematology autoanalyzers in the clinical laboratory improved the quality of the results of conventional blood count (CBC) parameters. In addition, these machines, especially those of last generation, have allowed introducing new parameters of great clinical utility. One of these new parameters is the reticulocyte hemoglobin that is emerging as a powerful tool in the diagnosis and management of iron-deficient erythropoiesis. Also is useful in several of its forms, particularly in absolute iron deficiency, functional iron deficiency, and iron sequestration. The reticulocyte hemoglobin in all cases where there is iron-deficient erythropoiesis is the first parameter detectable in the CBC, in turn; it is the first that is normalized when the administered therapy has been adequate. It has also proven to be cost effective, especially for being a CBC parameter more than an additional test. The only problem so far is that it is only available in some hematology autoanalyzers as those of Siemens and Sysmex companies, in its fourth generation models, also known as type-VI CBC or expanded or extended CBC. With this module pretends to present a new parameter that the medical community should incorporate as own and the clinical laboratories should be prepared to include it into their service portfolios as a new complementary tool in the prevention, detection, and management of iron-deficient erythropoiesis in its various manifestations.