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Rosaria Ingrassia, Maurizio Memo, Barbara Garavaglia
Mutations in WDR45 gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2)...
2017: Frontiers in Genetics
N P Kumar, B Velayutham, D Nair, S Babu
BACKGROUND: Circulating angiogenic factors of the vascular endothelial growth factor family are important biomarkers of disease severity in pulmonary tuberculosis (PTB). However, the role of angiopoietins, which are also involved in angiogenesis, in PTB is not known. OBJECTIVE AND DESIGN: To examine the association of circulating angiopoietins with TB disease or latent tuberculous infection (LTBI), we examined the systemic levels of angiopoietin (Ang) 1, Ang 2 and Tie-2 receptor in individuals with PTB (n = 44), LTBI (n = 44) or no tuberculous infection (NTBI) (n = 44)...
January 1, 2017: International Journal of Tuberculosis and Lung Disease
John B Porter, Maria Domenica Cappellini, Antonis Kattamis, Vip Viprakasit, Khaled M Musallam, Zewen Zhu, Ali T Taher
Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups...
January 2017: British Journal of Haematology
Richard Coffey, Mitchell D Knutson
The relationship between iron and β-cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β-cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β-cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZRT/IRT-like protein 14 and 8 (ZIP14 and ZIP8) and divalent metal-ion transporter-1 (DMT1) to iron uptake by human β-cells...
February 1, 2017: American Journal of Physiology. Cell Physiology
Suchaya Silvilairat, Pimlak Charoenkwan, Suwit Saekho, Adisak Tantiworawit, Arintaya Phrommintikul, Somdet Srichairatanakool, Nipon Chattipakorn
BACKGROUND: Iron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition. METHODS: One hundred and one patients with transfusion-dependent thalassemia were enrolled in this study...
2016: PloS One
Philipp Klahn, Mark Brönstrup
The development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted...
2016: Current Topics in Microbiology and Immunology
Anna L Peters, Renoja K Kunanayagam, Robin van Bruggen, Dirk de Korte, Nicole P Juffermans, Alexander P J Vlaar
BACKGROUND: Transfusion of a single unit of stored red blood cells (RBCs) has been hypothesized to induce supra-physiological levels of non-transferrin bound iron (NTBI), which may enhance inflammation and act as a nutrient for bacteria. We investigated the relation between RBC storage time and iron levels in a clinically relevant "two-hit" human transfusion model. STUDY DESIGN AND METHODS: Eighteen healthy male volunteers (ages 18-35 years) were infused with 2 ng lipopolysaccharide (LPS)/kg to induce systemic inflammatory response syndrome...
January 2017: Transfusion
Stella Maria Barrouin-Melo, Johanna Anturaniemi, Satu Sankari, Mikko Griinari, Faik Atroshi, Sakaewan Ounjaijean, Anna Katrina Hielm-Björkman
BACKGROUND: Oxidative stress plays an important role in the pathogenesis of disease, and the antioxidant physiological effect of omega-3 from fish oil may lead to improvement of canine spontaneous osteoarthritis (OA). METHODS: In this prospective randomized, controlled, double-blinded study, we assessed haematological and biochemical parameters in dogs with OA following supplementation with either a concentrated omega-3 deep sea fish oil product or corn oil. Blood samples from 77 client-owned dogs diagnosed as having OA were taken before (baseline) and 16 weeks after having orally ingested 0...
August 26, 2016: Lipids in Health and Disease
F van Markus-Doornbosch, A J de Kloet, M A M Berger, S A M Lambregts, R Wolterbeek, T P M Vliet Vlieland
OBJECTIVE: To assess the degree of fatigue in children and youth after traumatic and non-traumatic brain injury (TBI and NTBI) and related factors. METHOD: Follow-up study including patients with a hospital-based diagnosis of acquired brain injury (ABI), aged 4-20 years at onset and their parents. Parents and children (dependent on age) completed the Paediatric Quality of Life Inventory™ Multidimensional Fatigue Scale (PedsQL™ MFS), which measures general fatigue (GF), sleep/rest fatigue (SRF) and cognitive fatigue (CF)...
2016: Brain Injury: [BI]
Vincy Chan, Jason D Pole, Michelle Keightley, Robert E Mann, Angela Colantonio
BACKGROUND: Children and youth with non-traumatic brain injury (nTBI) are often overlooked in regard to the need for post-injury health services. This study provided population-based data on their burden on healthcare services, including data by subtypes of nTBI, to provide the foundation for future research to inform resource allocation and healthcare planning for this population. METHODS: A retrospective cohort study design was used. Children and youth with nTBI in population-based healthcare data were identified using International Classification of Diseases Version 10 codes...
July 20, 2016: BMC Neurology
Suwakon Wongjaikam, Sirinart Kumfu, Juthamas Khamseekaew, Jirapas Sripetchwandee, Somdet Srichairatanakool, Suthat Fucharoen, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Iron chelators are used to treat iron overload cardiomyopathy patients. However, a direct comparison of the benefits of three common iron chelators (deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX)) or an antioxidant (N-acetyl cysteine (NAC)) with a combined DFP and NAC treatments on left ventricular (LV) function with iron overload has not been investigated. METHODS AND FINDINGS: Male Wistar rats were fed with either a normal diet or a high iron diet (HFe group) for 4 months...
2016: PloS One
Maciej W Garbowski, Yongmin Ma, Suthat Fucharoen, Somdet Srichairatanakool, Robert Hider, John B Porter
Nontransferrin-bound iron (NTBI) is a heterogeneously speciated plasma iron, typically detectable when transferrin saturation (TfSat) exceeds 75%. Here, we examine factors affecting NTBI levels by a recently discovered direct chelator-based (CP851) fluorescent bead-linked flow-cytometric assay (bead-NTBI), compared with the established indirect nitrilotriacetate (NTA) assay in 122 iron-overloaded patients, including 64 on recent iron chelation therapy and 13 healthy volunteers. Both methods correlated (r = 0...
November 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
Shounak Baksi, Ajai K Tripathi, Neena Singh
Aggregation of α-synuclein (α-syn) in neurons of the substantia nigra is diagnostic of Parkinson's disease (PD), a neuro-motor disorder with prominent visual symptoms. Here, we demonstrate that α-syn, the principal protein involved in the pathogenesis of PD, is expressed widely in the neuroretina, and facilitates the uptake of transferrin-bound iron (Tf-Fe) by retinal pigment epithelial (RPE) cells that form the outer blood-retinal barrier. Absence of α-syn in knock-out mice (α-syn(-/-)) resulted in down-regulation of ferritin in the neuroretina, indicating depletion of cellular iron stores...
August 2016: Free Radical Biology & Medicine
Christopher M Tan, Charles J Gill, Jin Wu, Nathalie Toussaint, Jingjun Yin, Takayuki Tsuchiya, Charles G Garlisi, David Kaelin, Peter T Meinke, Lynn Miesel, David B Olsen, Armando Lagrutta, Hideyuki Fukuda, Ryuta Kishii, Masaya Takei, Kouhei Oohata, Tomoko Takeuchi, Taku Shibue, Hisashi Takano, Akinori Nishimura, Yasumichi Fukuda, Sheo B Singh
Oxabicyclooctane-linked novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of recently described antibacterial agents with broad-spectrum activity. NBTIs dually inhibit the clinically validated bacterial targets DNA gyrase and topoisomerase IV and have been shown to bind distinctly from known classes of antibacterial agents directed against these targets. Herein we report the molecular, cellular, and in vivo characterization of AM-8722 as a representative N-alkylated-1,5-naphthyridone left-hand-side-substituted NBTI...
August 2016: Antimicrobial Agents and Chemotherapy
Satoshi Ito, Katsuya Ikuta, Daisuke Kato, Addo Lynda, Kotoe Shibusa, Noriyasu Niizeki, Yasumichi Toki, Mayumi Hatayama, Masayo Yamamoto, Motohiro Shindo, Naomi Iizuka, Yutaka Kohgo, Mikihiro Fujiya
Non-Tf-bound iron (NTBI), which appears in serum in iron overload, is thought to contribute to organ damage; the monitoring of serum NTBI levels may therefore be clinically useful in iron-overloaded patients. However, NTBI quantification methods remain complex, limiting their use in clinical practice. To overcome the technical difficulties often encountered, we recently developed a novel automated NTBI quantification system capable of measuring large numbers of samples. In the present study, we investigated the in vivo behavior of NTBI in human and animal serum using this newly established automated system...
August 2016: International Journal of Hematology
Irene Cortés-Puch, Kenneth E Remy, Steven B Solomon, Junfeng Sun, Dong Wang, Mariam Al-Hamad, Seth M Kelly, Derek Sinchar, Landon Bellavia, Tamir Kanias, Mark A Popovsky, Daniel B Kim-Shapiro, Harvey G Klein, Charles Natanson
BACKGROUND: Massive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs...
November 2015: Transfusion
Alberto Roghi, Erika Poggiali, Lorena Duca, Antonio Mafrici, Patrizia Pedrotti, Stefania Paccagnini, Sergio Brenna, Alessio Galli, Dario Consonni, Maria Domenica Cappellini
BACKGROUND: Hereditary hemochromatosis, thalassemia and myelodysplastic syndromes represent disease models with evidence of iron-related heart failure. Non-Transferrin Bound Iron (NTBI) induces cardiac toxicity through the production of reactive oxygen species and lipid peroxidation. In ST-elevation acute myocardial infarction (STEMI) with evidence of microvascular obstruction (MVO) and hemorrhage (HEM), HEM may be a source of iron-related cardiac toxicity through NTBI and pro-inflammatory mediators...
November 15, 2015: International Journal of Cardiology
Steven B Solomon, Irene Cortés-Puch, Junfeng Sun, Kenneth E Remy, Dong Wang, Jing Feng, Sameena S Khan, Derek Sinchar, Daniel B Kim-Shapiro, Harvey G Klein, Charles Natanson
BACKGROUND: In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects. STUDY DESIGN AND METHODS: Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2...
November 2015: Transfusion
Husam Aljwaid, Desley L White, Keith J Collard, A John Moody, Jonathan H Pinkney
AIMS: To investigate the association between circulating non-transferrin-bound iron [NTBI], and markers of oxidative stress, endothelial function and inflammation in subjects with type 2 diabetes and non-diabetic subjects with varying degrees of obesity. METHODS: Plasma NTBI was measured by HPLC, together with total iron, iron-binding capacity, transferrin saturation and soluble transferrin receptor, together with total and reduced ascorbate, malondialdehyde [MDA], E-selectin and high-sensitivity c-reactive protein [hs-CRP] in groups of 28 subjects with type 2 diabetes, 28 non-obese controls and 17 obese non-diabetic subjects...
September 2015: Journal of Diabetes and its Complications
Franca Codazzi, Ilaria Pelizzoni, Daniele Zacchetti, Fabio Grohovaz
Iron plays a fundamental role in the development of the central nervous system (CNS) as well as in several neuronal functions including synaptic plasticity. Accordingly, neuronal iron supply is tightly controlled: it depends not only on transferrin-bound iron but also on non-transferrin-bound iron (NTBI), which represents a relevant quote of the iron physiologically present in the cerebrospinal fluid (CSF). Different calcium permeable channels as well as the divalent metal transporter 1 (DMT1) have been proposed to sustain NTBI entry in neurons and astrocytes even though it remains an open issue...
2015: Frontiers in Molecular Neuroscience
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