ascorbic-acid and Hematologic-Diseases

Ten-Eleven Translocation-2 (TET2) inactivation through loss-of-function mutation, deletion and IDH1/2 (Isocitrate Dehydrogenase 1 and 2) gene mutation is a common event in myeloid and lymphoid malignancies. TET2 gene mutations similar to those observed in myeloid and lymphoid malignancies also accumulate with age in otherwise healthy subjects with clonal hematopoiesis. TET2 is one of the three proteins of the TET (Ten-Eleven Translocation) family, which are evolutionarily conserved dioxygenases that catalyze the conversion of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC) and promote DNA demethylation. TET dioxygenases require 2-oxoglutarate, oxygen and Fe(II) for their activity, which is enhanced in the presence of ascorbic acid. TET2 is the most expressed TET gene in the hematopoietic tissue, especially in hematopoietic stem cells. In addition to their hydroxylase activity, TET proteins recruit the O-linked β-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) enzyme to chromatin, which promotes post-transcriptional modifications of histones and facilitates gene expression. The TET2 level is regulated by interaction with IDAX, originating from TET2 gene fission during evolution, and by the microRNA miR-22. TET2 has pleiotropic roles during hematopoiesis, including stem-cell self-renewal, lineage commitment and terminal differentiation of monocytes. Analysis of Tet2 knockout mice, which are viable and fertile, demonstrated that Tet2 functions as a tumor suppressor whose haploinsufficiency initiates myeloid and lymphoid transformations. This review summarizes the recently identified TET2 physiological and pathological functions and discusses how this knowledge influences our therapeutic approaches in hematological malignancies and possibly other tumor types.

Topics: Aging; Ascorbic Acid; Dioxygenases; DNA Methylation; DNA-Binding Proteins; Embryonic Stem Cells; Epigenesis, Genetic; Genes, Tumor Suppressor; Hematologic Diseases; Hematopoiesis; Humans; MicroRNAs; Mutation; Proto-Oncogene Proteins

Reactive oxygen species (ROS) such as the superoxide (O2.-) and the hydroxyl radical (OH.) are aggressive chemical compounds that can induce tissue injury, e.g. by peroxidation of polyunsaturated fatty acids in cell membranes or directly by DNA damage. Many pathological conditions are in part caused by ROS. There are various biological defense systems directed towards radicals: specific enzymes, e.g. superoxide dismutase or glutathione peroxidase; nonessential antioxidants, e.g. the plasma proteins and uric acid; and the essential antioxidants, e.g. vitamin C, vitamin E and carotenoids. This review focuses on various clinical conditions where ROS are of major pathogenetic significance: ageing, cancer, stroke, hematologic disorders, adult respiratory distress syndrome (ARDS) and organ preservation in transplantation medicine. Moreover, the complementary system of the vitamins C and E in defense against ROS is shortly discussed and the need for further studies about the effects of antioxidant treatment, such as interventional studies, proposed. The chronic exposure of the organism to ROS is an important factor for tissue injury in the process of ageing. Lipofuscin is a typical product of lipid peroxidation and inversely correlates with longevity of an organism. The ingestion of higher doses of antioxidative vitamins was recently shown to be protective for the development of cataracts, a degenerative disorder of the eye. The impairment of the immune system in elderly people might be prevented by a higher intake of multivitamin supplements. Whether supplementation with antioxidative vitamins can extend the life span in humans, as was shown in experimental animals, remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Antioxidants; Ascorbic Acid; Carotenoids; Cerebrovascular Disorders; Free Radicals; Hematologic Diseases; Humans; Neoplasms; Reactive Oxygen Species; Respiratory Distress Syndrome; Vitamin E

Topics: Anemia; Ascorbic Acid; Blood Coagulation Disorders; Chronic Disease; Folic Acid; Hematologic Diseases; Hemolysis; Humans; Leukocytosis; Mononuclear Phagocyte System; Serum Albumin; Stress, Physiological; Syndrome; Thrombocytosis; Zinc

Topics: Antineoplastic Agents; Ascorbic Acid; Glucosephosphate Dehydrogenase Deficiency; Hematologic Diseases; Humans; Male; Middle Aged; Oxidative Stress; Prostatic Neoplasms; Renal Insufficiency

To investigate the diet and nutritional status of hospitalized children with blood disease in order to provide nutritional guidelines.. The patients' daily dietary intakes, including breakfast, lunch, dinner and additional meals, were recorded in detail for seven consecutive days. The intake amount of various nutrients was calculated using the dietary database.. The majority of children with blood disease showed inadequate intakes of calories [mean 1825.81 kCal/d, 73.62% of the recommended intake (RNI)] and protein (mean 67.68 g/d, 81.34% of RNI). Intakes of vitamin E and riboflavin were adequate, but intakes of vitamin A, thiamine and vitamin C (66.67%, 77.78% and 69.89% of RNI, respectively) were inadequate. Iron and selenium intakes were adequate, but calcium and zinc intakes (41.11% and 56.21% of RNI, respectively) were grossly inadequate.. Hospitalized children with blood disease had decreased dietary intakes of calories, protein, vitamin A, vitamin C, thiamin, calcium and zinc. The dietary pattern and nutritional intake need to be improved.

Topics: Adolescent; Ascorbic Acid; Child; Child, Preschool; Energy Intake; Female; Hematologic Diseases; Hospitalization; Humans; Infant; Male; Nutritional Status; Reactive Oxygen Species; Selenium; Vitamin A; Zinc

The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to both the Emax and Sigmoid Emax models. The Emax values for MetHgb formation in rat blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 83 (8) and 84 (2)%, while the EC50 values were 1087 (283) and 828 (104) microM, respectively (mean +/- SD). Neither these values nor those generated for the Sigmoid Emax model differed significantly between the two metabolites. Similarly, the Emax values in human blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 79 (5) and 80 (2)%, while the EC50 values were 90 (17) and 95 (19) microM, respectively. These values also did not differ between the two metabolites using either pharmacodynamic model. MetHgb was produced at the same rate, reached similar peak concentrations, and exhibited the same rate of decline with both metabolites. The area under the MetHgb content versus time curve did not differ between the two metabolites. These data demonstrate that MADDS-NOH and DDS-NOH are equipotent and equally efficacious in their MetHgb-forming ability. Investigation of the disposition of these metabolites is necessary to assess their relative role in dapsone-induced toxicity in vivo.

Topics: Adult; Animals; Ascorbic Acid; Dapsone; Drug Stability; Hematologic Diseases; Humans; Male; Methemoglobin; Models, Biological; Rats; Rats, Sprague-Dawley; Species Specificity; Time Factors

T lymphocyte mobility is low in patients with low neutrophil mobility. Thymocytes move comparably with normal mature T lymphocytes. Histamine accelerates T lymphocyte mobility in healthy subjects, patients with defective lymphocyte mobility and thymocytes. Ascorbic acid increases lymphocyte mobility of healthy subjects and thymocytes. Inhibition of mobility of T- or Tmu-depleted T lymphocytes by complexed IgG casts doubt on previous reports that the T gamma cells do not move.

Topics: Adult; Antigen-Antibody Complex; Ascorbic Acid; Cell Movement; Child; Hematologic Diseases; Histamine; Humans; Immunoglobulin G; Middle Aged; Neutrophils; T-Lymphocytes; Thymus Gland

Topics: Animals; Ascorbic Acid; Glucose; Glycerol; Hematologic Diseases; Kidney Diseases; Rabbits

Leucocyte ascorbic acid was estimated in patients with abnormal leucocyte states and other haematological disorders. Levels below the normal range were found in most cases of chronic myeloid leukaemia and chronic lymphatic leukaemia. Subnormal levels were found in more than a third of patients with acute leukaemias, lymphomas, glandular fever, myelofibrosis, and polycythaemia, and in the same proportion of patients receiving cytotoxic drugs, and also in those with a polymorph leucocytosis and those with purpura. Most patients with anaemia but a normal leucocyte count, and those with myelomatosis had normal levels. The majority of pregnant women tested had subnormal levels. In a wide variety of leucocyte disorders the leucocyte ascorbic acid may not be an accurate index of the body's Vitamin C status. The results also support the supposition that leucocyte ascorbic acid is mostly carried by normal mature polymorphs.

Topics: Ascorbic Acid; Female; Hematologic Diseases; Humans; Leukocyte Count; Leukocytes; Male; Pregnancy

Topics: Ascorbic Acid; Female; Hematologic Diseases; Humans; Leukocytes; Pregnancy

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Chronic Disease; Female; Fibrinolysis; Hematologic Diseases; Humans; Hypertension; Male; Middle Aged; Nephritis

Topics: Adrenocorticotropic Hormone; Anemia; Anemia, Myelophthisic; Anti-Bacterial Agents; Ascorbic Acid; Benzene; Biopsy; Blood Transfusion; Cortisone; Female; Hematologic Diseases; Hematology; Leukemia; Liver Extracts; Mortality; Occupational Diseases; Pathology; Poisoning; Prednisolone; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Tetracycline; Toxicology; Vasopressins; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Ascorbic Acid; Ferrous Compounds; Fumarates; Hematologic Diseases; Humans; Iron

Topics: Ascorbic Acid; Chronic Disease; Hematologic Diseases; Humans; Lymphatic Diseases; Neoplasms; Vitamins

Topics: Ascorbic Acid; Erythroblastosis, Fetal; Fetus; Flavonoids; Hematologic Diseases; Nutrition Therapy; Vitamins

Topics: Animals; Ascorbic Acid; Bone Diseases; Cholestanes; Diet; Hematologic Diseases; Lactose; Rats; Vitamin D; Vitamins

Topics: Achlorhydria; Aged; Anemia; Ascorbic Acid; Hematologic Diseases; Humans; Iron; Polycythemia Vera; Vitamin B 12

Topics: Ascorbic Acid; Hematologic Diseases; Humans; Leptospirosis; Vitamins; Weil Disease

Topics: Ascorbic Acid; Cholesterol; Hematologic Diseases; Humans; Inflammation; Lipid Metabolism Disorders; Vitamins

Topics: Ascorbic Acid; Citrus; Erythroblastosis, Fetal; Fetus; Flavones; Flavonoids; Hematologic Diseases; Humans; Vitamins

Topics: Ascorbic Acid; Hematologic Diseases; Humans; Iron; Iron Compounds; Neoplasms; Penicillins; Vitamins

Topics: Ascorbic Acid; Blood Circulation; Cardiovascular Diseases; Disease; Hematologic Diseases; Humans; Physiological Phenomena; Vitamins