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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...
October 5, 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...
October 3, 2016: 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...
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)...
August 26, 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...
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...
June 7, 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
Karn Wijarnpreecha, Natthaphat Siri-Angkul, Krekwit Shinlapawittayatorn, Pimlak Charoenkwan, Suchaya Silvilairat, Chate Siwasomboon, Pannee Visarutratna, Somdet Srichairatanakool, Adisak Tantiworawit, Arintaya Phrommintikul, Siriporn C Chattipakorn, Nipon Chattipakorn
BACKGROUND: Iron-overload cardiomyopathy is a major cause of death in thalassemia patients due to the lack of an early detection strategy. Although cardiac magnetic resonance (CMR) T2* is used for early detection of cardiac iron accumulation, its availability is limited. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and found to be depressed in thalassemia. However, its direct correlation with cardiac iron accumulation has never been investigated. We investigated whether HRV can be used as an alternative indicator for early identification of cardiac iron deposition in thalassemia patients...
2015: PloS One
Nut Koonrungsesomboon, Adisak Tantiworawit, Arintaya Phrommintikul, Suwit Saekho, Somdet Srichairattanakool, Nipon Chattipakorn
Iron overload cardiomyopathy remains the major cause of death in β-thalassemia (β-thal). Conventional routine screening parameters such as serum ferritin and echocardiogram (ECG) do not permit early detection of this condition. Although non-transferrin-bound iron (NTBI) is a reliable indicator for iron overload, it is still not universally available. Recently, heart rate variability (HRV), representing cardiac autonomic function, was found to be depressed in thalassemia patients. We hypothesized that HRV can be used for early detection of iron overload cardiomyopathy...
2015: Hemoglobin
Supak Jenkitkasemwong, Chia-Yu Wang, Richard Coffey, Wei Zhang, Alan Chan, Thomas Biel, Jae-Sung Kim, Shintaro Hojyo, Toshiyuki Fukada, Mitchell D Knutson
Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14(-/-) mice with Hfe(-/-) and Hfe2(-/-) mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively...
July 7, 2015: Cell Metabolism
Arend J de Kloet, Rianne Gijzen, Lucia W Braga, Jorit J L Meesters, Jan W Schoones, Thea P M Vliet Vlieland
OBJECTIVES: Participation is considerably restricted in children and adolescents with acquired brain injury (ABI) as compared to their healthy peers. This systematic review aims to identify which factors are associated with participation in children and adolescents with ABI. METHODS: A systematic search in Medline and various other electronic databases from January 2001-November 2014 was performed. All clinical studies describing determinants of participation at least 1 year after the diagnosis of ABI by means of one or more pre-defined instruments in patients up to 18 years of age were included...
May 25, 2015: Brain Injury: [BI]
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