Interpreting SERUM FERRITIN
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Myoglobin Expression Under Hypoxic Condtions In
THESIS IN THE FACE OF HYPOXIA: MYOGLOBIN EXPRESSION UNDER HYPOXIC CONDTIONS IN CULTURED WEDDELL SEAL SKELETAL MUSCLE CELLS Submitted by Michael Anthony De Miranda Jr. Department of Biology In partial fulfillment of the requirements For the degree of Master of Science Colorado State University Fort Collins, Colorado Spring 2012 Master’s Committee: Advisor: Shane Kanatous Gregory Florant Scott Earley Copyright by Michael A. De Miranda Jr. 2012 All Rights Reserved ABSTRACT IN THE FACE OF HYPOXIA: MYOGLOBIN EXPRESSION UNDER HYPOXIC CONDITIONS IN CULTURED WEDDELL SEAL SKELETAL MUSCLE CELLS The hallmark adaptation to breath-hold diving in Weddell seals (Leptonychotes weddellii) is enhanced concentrations of myoglobin in their skeletal muscles. Myoglobin is a cytoplasmic hemoprotein that stores oxygen for use in aerobic metabolism throughout the dive duration. In addition, throughout the duration of the dive, Weddell seals rely on oxygen stored in myoglobin to sustain aerobic metabolism in which lipid is the primary contributor of acetyl CoA for the citric acid cycle. Together, enhanced myoglobin concentrations and a lipid-based aerobic metabolism represent some of the unique adaptations to diving found in skeletal muscle of Weddell seals. This thesis presents data that suggests cultured Weddell seal skeletal muscle cells inherently possess adaptations to diving such as increased myoglobin concentrations, and rely on lipids to fuel aerobic metabolism. I developed the optimum culture media for this unique primary cell line based on myoblast confluence, myoblast growth rates, myotube counts, and myotube widths. Once the culture media was established, I then determined the de novo expression of myoglobin under normoxic and hypoxic oxygen conditions and the metabolic profile of the myotubes under each oxygen condition. -
Evaluation of Iron Profile in Type II Diabetes Mellitus Cases
International Journal of Biotechnology and Biochemistry ISSN 0973-2691 Volume 15, Number 1 (2019) pp. 27-37 © Research India Publications http://www.ripublication.com Evaluation of Iron Profile in Type II Diabetes Mellitus Cases Dr. Sayantaann Saha*, Dr. Roopa Murgod Department of Biochemistry Vydehi Institute of Medical Sciences and Research Centre, EPIP Area, Whitefield, Bangalore 560066, India. ABSTRACT Introduction: Type 2 diabetes mellitus is the most common metabolic disorder, characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Iron, a transitional metal has been shown to play a major role in pathogenesis of T2DM with a bi-directional relationship where iron affects glucose metabolism, and glucose metabolism in turn impinges on several iron metabolic pathways. Aims or Objectives: To estimate and compare the parameters related to iron metabolism viz. Serum Iron (Fe), Serum Ferritin, Serum TIBC (Total Iron Binding Capacity), Serum Transferrin and Transferrin Saturation with Fasting Blood Sugar (FBS) between T2DM patients and healthy controls and correlation of FBS with the above iron parameters. Material and methods: A case control study was conducted between 41 cases of confirmed T2DM patients and 40 age & sex matched healthy controls. Iron profile parameters & FBS were estimated in both the groups and compared. Iron parameters were also correlated with FBS. * Corresponding author(Dr. Sayantaann Saha), Email id: [email protected] 28 Dr. Sayantaann Saha, Dr. Roopa Murgod Results: Serum ferritin, Serum iron & serum transferrin saturation were found to be significantly higher in patients with T2DM compared to control group (P<0.001). Serum transferrin & serum TIBC were found to be slightly lower in cases as compared to controls (P<0.001). -
Iron Regulation by Hepcidin
Iron regulation by hepcidin Ningning Zhao, … , An-Sheng Zhang, Caroline A. Enns J Clin Invest. 2013;123(6):2337-2343. https://doi.org/10.1172/JCI67225. Science in Medicine Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physiologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulation of hepcidin is found in many disease states, such as the anemia of chronic disease, iron refractory iron deficiency anemia, cancer, hereditary hemochromatosis, and ineffective erythropoiesis, such as β- thalassemia. Thus, the regulation of hepcidin is the subject of interest for the amelioration of the detrimental effects of either iron deficiency or overload. Find the latest version: https://jci.me/67225/pdf Science in medicine Iron regulation by hepcidin Ningning Zhao, An-Sheng Zhang, and Caroline A. Enns Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, Oregon, USA. Hepcidin is a key hormone that is involved in the control of iron homeostasis in the body. Physi- ologically, hepcidin is controlled by iron stores, inflammation, hypoxia, and erythropoiesis. The regulation of hepcidin expression by iron is a complex process that requires the coordination of multiple proteins, including hemojuvelin, bone morphogenetic protein 6 (BMP6), hereditary hemochromatosis protein, transferrin receptor 2, matriptase-2, neogenin, BMP receptors, and transferrin. Misregulation of hepcidin is found in many disease states, such as the anemia of chronic disease, iron refractory iron deficiency anemia, cancer, hereditary hemochromatosis, and ineffective erythropoiesis, such as β-thalassemia. -
Hepcidin Is Not a Marker of Chronic Inflammation in Atherosclerosis Hepcidin Aterosklerozda Kronik Inflamasyonun Bir Göstergesi De¤Ildir
Original Investigation Orijinal Araflt›rma 239 Hepcidin is not a marker of chronic inflammation in atherosclerosis Hepcidin aterosklerozda kronik inflamasyonun bir göstergesi de¤ildir Aytekin O¤uz, Mehmet Uzunlulu, Nezih Hekim* Department of Internal Medicine, Göztepe Training and Research Hospital, ‹stanbul, Turkey *Pakize Tarz› Laboratory, ‹stanbul, Turkey ABSTRACT Objective: To investigate the relationship between atherosclerosis, an inflammatory disease and hepcidin which is reported as an indi- cator of inflammation Methods: A total of 75 subjects between 40 and 70 years of age were included in the study. The patient group consisted of 40 stable pa- tients who had previously experienced an atherosclerotic event (18 women, 22 men; mean age 56.4±7.1 years). There were two control groups. The first control group consisted of 19 healthy subjects (11 women, 8 men; mean age 52.6± 7.4 years), while the second group inc- luded 16 patients (11 women, 5 men; mean age 56.5±9.3 years) with rheumatoid arthritis and anemia (diseased control group). Hepcidin measurement was performed using Hepcidin Prohormone ELISA (Solid Phase Enzyme-Linked Immunosorbent Assay) test kit. Results: Mean serum hepcidin levels were 243.2±48.8 ng/ml, 374.5±86.4 ng/ml, and 234±59.9 ng/ml in the patient group, in diseased cont- rols, and in healthy controls, respectively. Hepcidin levels were higher in diseased controls compared to the patient group and healthy controls (p=0.001). There were no significant differences between the patient group and healthy controls. Conclusion: These findings did not support the hypothesis that hepcidin levels could be increased in atherosclerotic cardiovascular di- seases as a marker of chronic inflammation. -
HEMOCHROMATOSIS GENOTYPES and ELEVATED TRANSFERRIN SATURATION - Risk of Diabetes Mellitus, Hypertension,Cancer, and Total Mortality
Doctor of Medical Science Thesis by Christina Ellervik MD, PhD HEMOCHROMATOSIS GENOTYPES AND ELEVATED TRANSFERRIN SATURATION - risk of diabetes mellitus, hypertension,cancer, and total mortality Aected Unaected Carrier Carrier Carrier Father Mother Aected Carrier Carrier Unaected Son Daughter Son Daughter Hemochromatosis genotypes and elevated transferrin saturation - risk of diabetes mellitus, hypertension,cancer, and total mortality Doctor of Medical Science Thesis by Christina Ellervik MD,PhD PhD The Faculty of Health and Medical Sciences at the University of Copenhagen has accepted this dissertation, which consists of the already published dissertations listed below, for pub- lic defence for the doctoral degree in medicine. Copenhagen, October 11th 2015 Ulla M. Wewer Head of Faculty Place and time for defence: St. Auditorium at Herlev Hospital, June 22nd 2016 at 2pm Table of Contents • Papers on which the thesis is based............................................................. 2 • Preface ............................................................................................................. 3 • Scope and delimitation of the thesis ...................................................... 3 - 4 • Introduction ............................................................................................ 4 - 14 Hereditary hemochromatosis ............................................................................................ 4 - 7 Diabetes mellitus (paper 1 and 2) ..................................................................................... -
The Acute Phase Response and Exercise: Court and Field Sports
170 Br J Sports Med 2001;35:170–173 The acute phase response and exercise: court and Br J Sports Med: first published as 10.1136/bjsm.35.3.170 on 1 June 2001. Downloaded from field sports K E Fallon, S K Fallon, T Boston Abstract capacity, and transferrin, and transferrin satu- Objective—To determine the presence or ration.45 absence of an acute phase response after A number of studies have documented training for court and field sports. aspects of the acute phase response after exer- Participants—All members of the Aus- cise of a duration that would be expected to tralian women’s soccer team (n = 18) and induce significant damage to skeletal 6–12 all members of the Australian Institute of muscle. No data are available on the acute Sport netball team (n = 14). phase response in relation to court and field Methods—Twelve acute phase reactants sports. (white blood cell count, neutrophil count, Documentation of the extent and nature of platelet count, serum iron, ferritin, and the acute phase response to various types of transferrin, percentage transferrin satu- exercise is important, as changes related to the response may need to be taken into account for ration, á1 antitrypsin, caeruloplasmin, á2 acid glycoprotein, C reactive protein, and interpretation of haematological and biochemi- erythrocyte sedimentation rate) were cal measurements made during and after participation in sport. measured during a rest period and after The aim of this prospective study was there- moderate and heavy training weeks in fore to determine the presence or absence of members of elite netball and women’s the acute phase response in sports representa- soccer teams. -
Section 8: Hematology CHAPTER 47: ANEMIA
Section 8: Hematology CHAPTER 47: ANEMIA Q.1. A 56-year-old man presents with symptoms of severe dyspnea on exertion and fatigue. His laboratory values are as follows: Hemoglobin 6.0 g/dL (normal: 12–15 g/dL) Hematocrit 18% (normal: 36%–46%) RBC count 2 million/L (normal: 4–5.2 million/L) Reticulocyte count 3% (normal: 0.5%–1.5%) Which of the following caused this man’s anemia? A. Decreased red cell production B. Increased red cell destruction C. Acute blood loss (hemorrhage) D. There is insufficient information to make a determination Answer: A. This man presents with anemia and an elevated reticulocyte count which seems to suggest a hemolytic process. His reticulocyte count, however, has not been corrected for the degree of anemia he displays. This can be done by calculating his corrected reticulocyte count ([3% × (18%/45%)] = 1.2%), which is less than 2 and thus suggestive of a hypoproliferative process (decreased red cell production). Q.2. A 25-year-old man with pancytopenia undergoes bone marrow aspiration and biopsy, which reveals profound hypocellularity and virtual absence of hematopoietic cells. Cytogenetic analysis of the bone marrow does not reveal any abnormalities. Despite red blood cell and platelet transfusions, his pancytopenia worsens. Histocompatibility testing of his only sister fails to reveal a match. What would be the most appropriate course of therapy? A. Antithymocyte globulin, cyclosporine, and prednisone B. Prednisone alone C. Supportive therapy with chronic blood and platelet transfusions only D. Methotrexate and prednisone E. Bone marrow transplant Answer: A. Although supportive care with transfusions is necessary for treating this patient with aplastic anemia, most cases are not self-limited. -
Emerging and Dynamic Biomedical Uses of Ferritin
pharmaceuticals Review Emerging and Dynamic Biomedical Uses of Ferritin Brian Chiou and James R. Connor * Department of Neurosurgery, Penn State College of Medicine, Hershey, PA 17033, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-717-531-4541 Received: 24 October 2018; Accepted: 12 November 2018; Published: 13 November 2018 Abstract: Ferritin, a ubiquitously expressed protein, has classically been considered the main iron cellular storage molecule in the body. Owing to the ferroxidase activity of the H-subunit and the nucleation ability of the L-subunit, ferritin can store a large amount of iron within its mineral core. However, recent evidence has demonstrated a range of abilities of ferritin that extends well beyond the scope of iron storage. This review aims to discuss novel functions and biomedical uses of ferritin in the processes of iron delivery, delivery of biologics such as chemotherapies and contrast agents, and the utility of ferritin as a biomarker in a number of neurological diseases. Keywords: ferritin; iron; iron delivery; nanotechnology; nanocage; drug delivery; inflammation; serum biomarker 1. Ferritin Introduction Ferritin, a protein originally identified in 1937 by Vilém Laufberger [1], is a ubiquitously expressed iron storage protein most commonly characterized by its ability to accumulate and store up to 4500 atoms of iron [2]. Ferritin consists of 24 subunits, typically comprised of different ratios of the H and L chain subunit. The ratios vary by organ and even by cell type. Importantly, the different subunits have divergent functions—H-ferritin utilizes ferroxidase activity that is necessary for the oxidation of ferrous (Fe2+) to ferric (Fe3+) iron while L-ferritin contains acidic residues on the surface cavity of the protein that facilitate ferroxidase turnover and are crucial for the nucleation of ferric iron within the core of the fully formed protein. -
Cold Type Autoimmune Hemolytic Anemia- a Rare Manifestation Of
Dematapitiya et al. BMC Infectious Diseases (2019) 19:68 https://doi.org/10.1186/s12879-019-3722-z CASE REPORT Open Access Cold type autoimmune hemolytic anemia- a rare manifestation of infectious mononucleosis; serum ferritin as an important biomarker Chinthana Dematapitiya1*, Chiara Perera2, Wajira Chinthaka1, Solith Senanayaka1, Deshani Tennakoon1, Anfas Ameer1, Dinesh Ranasinghe1, Ushani Warriyapperuma1, Suneth Weerarathna1 and Ravindra Satharasinghe1 Abstract Background: Infectious mononucleosis is one of the main manifestations of Epstein – Barr virus, which is characterized by fever, tonsillar-pharyngitis, lymphadenopathy and atypical lymphocytes. Although 60% of patients with IMN develop cold type antibodies, clinically significant hemolytic anemia with a high ferritin level is very rare and validity of serum ferritin as an important biomarker has not been used frequently. Case presentation: 18-year-old girl presented with fever, malaise and sore throat with asymptomatic anemia, generalized lymphadenopathy, splenomegaly and mild hepatitis. Investigations revealed that she had cold type autoimmune hemolysis, significantly elevated serum ferritin, elevated serum lactate dehydrogenase level with serological evidence of recent Epstein Barr infection. She was managed conservatively and her hemoglobin and serum ferritin levels normalized without any intervention following two weeks of the acute infection. Conclusion: Cold type autoimmune hemolytic anemia is a rare manifestation of infectious mononucleosis and serum ferritin is used very rarely as an important biomarker. Management of cold type anemia is mainly supportive and elevated serum ferritin indicates severe viral disease. Keywords: Infectious mononucleosis (IMN), Hemolytic anemia, Ferritin Background mainly Mycoplasma pneumoniae and infectious mono- Epstein – Barr virus is one of the most ubiquitous human nucleosis (IMN). Diagnosis of cold type AIHA due to viruses, infecting more than 95% the adult population IMN is confirmed by demonstrating red cell aggregates in worldwide. -
Hepcidin Therapeutics
pharmaceuticals Review Hepcidin Therapeutics Angeliki Katsarou and Kostas Pantopoulos * Lady Davis Institute for Medical Research, Jewish General Hospital, Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-(514)-340-8260 (ext. 25293) Received: 3 November 2018; Accepted: 19 November 2018; Published: 21 November 2018 Abstract: Hepcidin is a key hormonal regulator of systemic iron homeostasis and its expression is induced by iron or inflammatory stimuli. Genetic defects in iron signaling to hepcidin lead to “hepcidinopathies” ranging from hereditary hemochromatosis to iron-refractory iron deficiency anemia, which are disorders caused by hepcidin deficiency or excess, respectively. Moreover, dysregulation of hepcidin is a pathogenic cofactor in iron-loading anemias with ineffective erythropoiesis and in anemia of inflammation. Experiments with preclinical animal models provided evidence that restoration of appropriate hepcidin levels can be used for the treatment of these conditions. This fueled the rapidly growing field of hepcidin therapeutics. Several hepcidin agonists and antagonists, as well as inducers and inhibitors of hepcidin expression have been identified to date. Some of them were further developed and are currently being evaluated in clinical trials. This review summarizes the state of the art. Keywords: iron metabolism; hepcidin; ferroportin; hemochromatosis; anemia 1. Systemic Iron Homeostasis Iron is an essential constituent of cells and organisms and participates in vital biochemical activities, such as DNA synthesis, oxygen transfer, and energy metabolism. The biological functions of iron are based on its capacity to interact with proteins and on its propensity to switch between the ferrous (Fe2+) and ferric (Fe3+) oxidation states. -
K392-100 Total Iron-Binding Capacity (TIBC) and Serum Iron Assay Kit (Colorimetric)
FOR RESEARCH USE ONLY! Total Iron-Binding Capacity (TIBC) and Serum Iron Assay Kit (Colorimetric) rev 08/19 (Catalog # K392-100; 100 assays; Store at -20°C) I. Introduction: BioVision’s TIBC and Serum Iron Assay Kit measures both Total iron-binding capacity (TIBC) and Serum iron. Those values indicate the requisite iron for transferrin saturation and Serum Iron respectively. In humans, Transferrin is a blood protein that binds and transports iron throughout the body. Iron bound to transferrin and not bound are reflected in the following: 1) Total Iron Binding Capacity, 2) Unbound Iron, 3) Transferrin Saturation Bound Iron, and 4) Free Iron. Those measurements can be used for to detect and monito transferrin saturation and also iron-deficiency anemia and chronic inflammatory diseases. Part A: TIBC Part B: Serum Iron 1 1 2 2 3 3 4 II. Application: Determination of TIBC, Unbound Iron, Transferrin Saturation, Serum Iron III. Sample Type: Serum or plasma. Serum-off-the clot is preferable to normal serum. IV. Kit Contents: Components K392-100 Cap Code Part Number TIBC Assay Buffer 25 ml WM K392-100-1 Iron Solution 100 µl Blue K392-100-2 TIBC Detector 2 x 1.5 ml Brown K392-100-3 TIBC Developer 5 ml NM K392-100-4 Iron Standard (100 mM) 100 µl Yellow K392-100-5 V. User Supplied Reagents and Equipment: • 96-well plate clear plate with flat bottom • Microplate reader capable of absorbance reading VI. Storage Conditions and Reagent Preparation: Store kit at -20°C, protected from light. Briefly centrifuge small vials prior to opening. -
Gamma-Glutamyltransferase: a Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk
Hindawi Publishing Corporation Disease Markers Volume 2015, Article ID 818570, 18 pages http://dx.doi.org/10.1155/2015/818570 Review Article Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk Gerald Koenig1,2 and Stephanie Seneff3 1 Health-e-Iron, LLC, 2800 Waymaker Way, No. 12, Austin, TX 78746, USA 2Iron Disorders Institute, Greenville, SC 29615, USA 3Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA Correspondence should be addressed to Gerald Koenig; [email protected] Received 2 July 2015; Accepted 20 September 2015 Academic Editor: Ralf Lichtinghagen Copyright © 2015 G. Koenig and S. Seneff. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol-related liver disease. However, GGT’s predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF) levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep.