ascorbic-acid and Autoimmune-Diseases

Hyperhomocysteinemia causes connective tissue pathology. Several theories on the mechanism of homocysteine toxicity in connective tissue are reviewed briefly. A possible new mechanism was revealed recently in the discovery of a reaction in which homocysteine thiolactone is converted to mercaptopropionaldehyde. The reaction is the Strecker degradation of amino acids in which ninhydrin is replaced by the structurally similar dehydroascorbic acid. The reaction may occur in vivo and may be pathogenic to connective tissue in four ways: (1) the reaction may deplete ascorbic acid that is required for collagen synthesis, (2) the mercaptoaldehyde product may interfere with collagen synthesis, (3) the mercaptoaldehyde may cause abnormal cross-linking of collagen molecules, and (4) the mercaptoaldehyde may attach to collagen molecules rendering them antigenic and triggering an autoimmune response.

Topics: Animals; Aryldialkylphosphatase; Ascorbic Acid; Autoimmune Diseases; Collagen; Connective Tissue Diseases; Homocysteine; Humans; Hyperhomocysteinemia; Sulfhydryl Compounds

Idiopathic thrombocytopenic purpura (ITP) belongs to the family of autoimmune diseases. The term "idiopathic", however, is no longer correct as it is in fact an immunologically-related thrombocytopenia. This is why nowadays it is referred to as immune thrombopenia. Clinically the acute and chronic forms of ITP can be distinguished. We discuss the different forms of treatment based upon data provided by various studies of ITP. If treatment with prednisone or with gammaglobulins fails, or after unsuccessful splenectomy, then alternative experimental therapies may have to be used. Some of these treatments are described with reference to their therapeutic benefit and their function.

Topics: Acute Disease; Adrenal Cortex Hormones; Adult; Antineoplastic Agents; Ascorbic Acid; Autoimmune Diseases; Child; Chronic Disease; Danazol; Drug Therapy, Combination; Female; gamma-Globulins; Humans; Immunoglobulins; Interferons; Isoantibodies; Purpura, Thrombocytopenic; Rh-Hr Blood-Group System; Rho(D) Immune Globulin; Splenectomy

Chronic ITP is a common hematologic illness. Approximately three fourths of the patients respond to corticosteroids or splenectomy and need no further treatment. Patients refractory to these two therapeutic approaches are relatively resistant to present forms of treatment and are at much greater risk for morbidity and mortality. Future clinical studies evaluating therapy in this refractory group would be best performed in a cooperative group setting in which large numbers of patients could be treated in a prospective randomized manner.

Topics: Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal; Ascorbic Acid; Autoimmune Diseases; Azathioprine; Colchicine; Cyclophosphamide; Cyclosporins; Danazol; Female; gamma-Globulins; Humans; Methylprednisolone; Plasmapheresis; Platelet Transfusion; Pregnancy; Pregnancy Complications, Hematologic; Purpura, Thrombocytopenic; Splenectomy; Vinca Alkaloids

Reactive oxygen metabolic products derived from an activated NADPH oxidase present in the cell membrane of PMNs and mononuclear phagocytic cells play a critical role in the host's defense against bacterial infection. Recent studies have also demonstrated the ability of these toxic products to initiate eukaryotic cell injury and promote the development of the acute inflammatory responses. Experimental studies suggest that neutrophil-derived oxygen metabolites contribute to the development of the tissue injury associated with a variety of disease states, including emphysema, myocardial infarction, adult respiratory distress syndrome, immune complex-mediated vasculitis, and rheumatoid arthritis. Future studies to define further the mechanisms by which reactive oxygen-derived metabolic products mediate tissue injury will provide insight into the development of new therapeutic strategies for the modulation of disease states that are mediated by the recruitment and activation of PMNs.

Topics: Animals; Arthritis, Rheumatoid; Ascorbic Acid; Autoimmune Diseases; Ceruloplasmin; Chemotactic Factors; Cricetinae; Cricetulus; Free Radicals; Humans; Immune Complex Diseases; Inflammation; Lipid Peroxides; Myocardial Infarction; NADH, NADPH Oxidoreductases; NADPH Oxidases; Neutrophils; Oxidation-Reduction; Oxygen; Pancreatic Elastase; Peroxidase; Peroxidases; Peroxides; Phagocytosis; Pulmonary Emphysema; Respiratory Distress Syndrome; Superoxide Dismutase; Superoxides; Vasculitis; Vitamin E

Topics: Adult; Anaphylaxis; Animals; Antibody Formation; Ascorbic Acid; Autoimmune Diseases; Bacterial Infections; Chemotaxis; Common Cold; Female; Humans; Immunity, Cellular; Male; Phagocytes; Phagocytosis; T-Lymphocytes; Virus Diseases

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Agranulocytosis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Ascorbic Acid; Autoantibodies; Autoimmune Diseases; Blood Transfusion; Chloroquine; Colitis; Colitis, Ulcerative; Drug Hypersensitivity; Drug Therapy; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Humans; Internal Medicine; Leukopenia; Lupus Erythematosus, Systemic; Neutrophils; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Splenectomy; Thrombocytopenia; Thyroiditis; Toxicology; Vitamins

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring's risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997-2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.

Topics: Adult; Ascorbic Acid; Autoimmune Diseases; Child, Preschool; Diabetes Mellitus, Type 1; Diet; Diet Surveys; Dietary Supplements; Female; Finland; Genotype; HLA Antigens; Humans; Infant; Iron, Dietary; Islets of Langerhans; Male; Maternal Exposure; Maternal Nutritional Physiological Phenomena; Pregnancy; Prenatal Exposure Delayed Effects; Proportional Hazards Models; Prospective Studies; Regression Analysis

Canonical neutrophil antimicrobial effector mechanisms, such as degranulation, production of reactive oxygen species, and release of neutrophil extracellular traps (NETs), can result in severe pathology. Activation of neutrophils through immune complexes (ICs) plays a central role in the pathogenesis of many autoimmune inflammatory diseases. In this study, we report that immobilized ICs (iICs), which are hallmarks of several autoimmune diseases, induce the release of NETs from primary human neutrophils. The iIC-induced NET formation was found to require production of reactive oxygen species by NADPH oxidase and myeloperoxidase and to be mediated by FcγRIIIb. Blocking of the β2 integrin macrophage-1 Ag but not lymphocyte function-associated Ag-1 abolished iIC-induced NET formation. This suggests that FcγRIIIb signals in association with macrophage-1 Ag. As intracellular signaling pathways involved in iIC-induced NET formation we identified the tyrosine kinase Src/Syk pathway, which downstream regulates the PI3K/Akt, p38 MAPK, and ERK1/2 pathways. To our knowledge, the present study shows for the first time that iICs induce NET formation. Thus, we conclude that NETs contribute to pathology in autoimmune inflammatory disorders associated with surface-bound ICs.

Topics: Aminopyrine; Antigen-Antibody Complex; Antioxidants; Ascorbic Acid; Autoimmune Diseases; Butadienes; CD11a Antigen; CD18 Antigens; Cell Degranulation; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases; GPI-Linked Proteins; Humans; Imidazoles; Inflammation; Intracellular Signaling Peptides and Proteins; Lymphocyte Function-Associated Antigen-1; Macrophage-1 Antigen; Mesalamine; Neutrophil Activation; Neutrophils; Nitriles; Onium Compounds; p38 Mitogen-Activated Protein Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-akt; Pyridines; Pyrimidines; Reactive Oxygen Species; Receptors, IgG; src-Family Kinases; Syk Kinase

To evaluate the effect of intravenous immunoglobulin (IVIG) and vitamin C on the progression of experimental autoimmune myocarditis(EAM).. Fifty-two Balb/c mice were randomized into six groups: The blank group received no treatment, the remaining 5 groups were immunized with 100mug emulsified porcine myosin at d 1 and d 7. Different agents were injected from d 1, SVitC group:150 mg/kg*d(-1)vitamin C; LVitC group: 300 mg/kg*d(-1)vitamin C; IVIG group: 1 g/kg*d(-1)IVIG; IVIG+VitC group: 1 g/kg*d(-1)IVIG and 150 mg/kg*d(-1)vitamin C; The control group same volume of normal saline. All mice were sacrificed at d 21, and serum TNF-alpha levels were detected with enzyme linked immunosorbent assay (ELISA). The ratio of heart to body weight(C/W), spleen to body weight(S/W) and kidney to body weigh(R/W) were calculated. The spleens and heart were examined pathologically and/or immunohistochemically.. Compared with those of control group, inflammatory cells infiltration in the myocardium and calcification in the pericardiume in SVitC and LVitC groups were extenuated. There were inflammatory cells infiltrating in the myocardium sparely and no calcification in the pericardium in IVIG and IVIG+VitC groups. The size of spleens enlarged especially in IVIG and IVIG+VitC groups. White and red pulps of spleens were hyperplastic microscopically. The C/W of treatment groups decreased significantly compared with that of control group. The S/W of therapy groups and control group was significantly higher than that of blank group; and the S/W of IVIG and IVIG + VitC groups was significantly higher than that of SVitC and LVitC groups. The R/W in each groups had no significant difference. The TNF-alpha level in SVitC and LVitC groups was a little lower than that in control group; TNF-alpha level in IVIG and IVIG+VitC groups was significantly lower than that of control group. Wide fluorescence stripe was found along extracellular matrix surrounding the damaged cardiomyocytes of control group. Both density and intensity of fluorescence in SVitC and LVitC groups were lower than those of control group. There were much wider fluorescence stripe and strengthened intensity in IVIG and IVIG + VitC groups. The myofilaments were in wild disorder and sarcomere had severe breakage in control group. Moreover, chondriosome hypertrophy and vacuolar degeneration were found. The damage lessened in SVitC and LVitC groups. Both myofilaments and sarcomeres in IVIG and IVIG + VitC groups were almost normal, and the chondriosome was normal.. IVIG and vitamin C have some protective and therapeutic effect on the progression of EAM by decreasing pathological damage of myocardium and depressing TNF-alpha production, and IVIG combined with vitamin C is more effective.

Topics: Animals; Ascorbic Acid; Autoimmune Diseases; Drug Therapy, Combination; Female; gamma-Globulins; Immunoglobulins, Intravenous; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Myocarditis; Random Allocation; Tumor Necrosis Factor-alpha

The aim was to evaluate the efficacy of intravenous-immunoglobulin (IVIG) and vitamin C (VC) on the progression of experimental autoimmune myocarditis (EAM).. Fifty-two Balb/c mice were randomized into six groups: blank, small-dosage VC, large-dosage VC, IVIG, IVIG+VC, and a control group. All mice were sacrificed 21 days later. The level of tumor necrosis factor alpha (TNF-alpha), the ratios of the heart, spleen, and kidney to body weight (C/W, S/W, K/W), and pathological changes in the hearts and spleens were evaluated.. VC could extenuate inflammatory cell infiltration in the myocardium and calcification in the pericardium. IVIG or IVIG+VC could extenuate the pathological change more effectively. The C/W of each therapy group decreased significantly compared with that of control group. The TNF-alpha levels in the small- and large-dosage VC groups were a little lower than in the control group; the levels in the IVIG and IVIG+VC groups were significantly lower than in controls. Electron microscopic observation of the myocardium showed that VC could extenuate the damage to the myocardium. The myocardium in IVIG and IVIG+VC groups were almost normal.. IVIG and vitamin C have some protective and therapeutic effect on the progression of EAM by decreasing pathological damage to the myocardium and depressing TNF-alpha production. Especially IVIG combined with vitamin C are more effective as they can stimulate the immune reaction and increase IgG deposition in the myocardium.

Topics: Animals; Ascorbic Acid; Autoimmune Diseases; Female; Immunoglobulins, Intravenous; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron, Transmission; Myocarditis; Myocardium; Tumor Necrosis Factor-alpha

An unclassified amicrobial pustular dermatosis particularly affecting the main cutaneous folds, external auditory canals and scalp and coexisting with systemic lupus erythematosus has been recently described.. We studied 3 young females bearing such cutaneous manifestations in association with subacute cutaneous lupus erythematosus, celiac disease and various serum autoantibodies, respectively, in order to further characterize this possibly new entity.. Various routine and immunological laboratory tests, histopathologic and direct immunofluorescence examinations and in vitro studies of neutrophil function were performed in each patient.. We reported our findings and compared our cases with the few others appearing in the literature. We documented an impaired neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to be one of the verifying criteria.. All of these cases may represent a distinctive form in the clinicopathological spectrum of neutrophilic dermatoses (ND) because of the typical distribution and the close link with different autoimmune disorders. Cimetidine in combination with ascorbic acid can be indicated as an effective and safe alternative to the classic medications of ND, although the action of both drugs remains unexplained.

Topics: Adult; Ascorbic Acid; Autoantibodies; Autoimmune Diseases; Celiac Disease; Chemotaxis, Leukocyte; Cimetidine; Ear Canal; Female; Fluorescent Antibody Technique, Direct; Histamine H2 Antagonists; Humans; Lupus Erythematosus, Cutaneous; Neutrophils; Scalp Dermatoses; Skin; Skin Diseases, Vesiculobullous

The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopausal women, and four eumenorrheic women served as controls. Ovarian growth blocking IgGs were found in 21 of the 26 premature ovarian failure (POF) cases. The few cases characterized by the absence of follicles (streak ovaries) and the controls were negative. The ovarian blocking IgGs were far more prevalent in the POF cases than anti-cytoplasmic ovarian antibodies detected by an indirect immunofluorescence assay (only one of the 26 POF patients was positive). Our data hence confirm earlier expressed views that immune mechanisms are involved in a high proportion of patients with POF.

Topics: Adult; Ascorbic Acid; Autoimmune Diseases; DNA Replication; Female; Follicle Stimulating Hormone; Granulosa Cells; Humans; Immunoglobulin G; Immunoglobulins; In Vitro Techniques; Kinetics; Luteinizing Hormone; Menopause; Menopause, Premature; Menstruation; Ovarian Diseases; Radioimmunoassay; Reference Values

A 2-year-old girl presented with gonadotrophin-independent precocious puberty due to ovarian follicles. Central precocious puberty was excluded by several GnRH-tests and overnight LH sampling. There were no signs of McCune-Albright syndrome. An ovarian tumour was excluded by laparotomy and biopsies. Abdominal sonography demonstrated follicles occurring mostly in the left, sometimes in the right, ovary. Immunoglobulin G (IgG) purified from the patient's serum was capable of stimulating DNA synthesis in granulosa cells of rat ovarian segments kept in organ culture. Since FSH had a similar in-vitro action it is hypothesized that this patient's IgG mimics the action of FSH.

Topics: Animals; Ascorbic Acid; Autoimmune Diseases; Corpus Luteum; Cytotoxicity Tests, Immunologic; DNA; Estradiol; Female; Follicle Stimulating Hormone; Follicular Cyst; Granulosa Cells; Humans; Immunoglobulin G; Infant; Leydig Cells; Luteinizing Hormone; Male; Puberty, Precocious; Rats; Rats, Inbred Strains

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Autoimmune Diseases; Chronic Disease; Female; Humans; Male; Middle Aged; Purpura, Thrombocytopenic

Antioxidants (ascorbic acid, glutathione, cysteine, alpha-tocopherol) and uric acid were measured using two high-pressure liquid chromatographic methods in 3 regions (cervical, thoracic, lumbar) of the spinal cord and in blood of Lewis rats during the attack and recovery of experimental autoimmune encephalomyelitis (EAE). Uric acid, which is thought to be a marker of free radical release, was greatly increased and glutathione correspondingly decreased in lumbar and thoracic regions. Cysteine and ascorbic acid were practically unchanged, whereas alpha-tocopherol was significantly increased during attack and recovery. Results, which could have therapeutic implications, generally support the hypothesis that free radicals are released during EAE.

Topics: Animals; Antioxidants; Ascorbic Acid; Autoimmune Diseases; Cysteine; Encephalomyelitis; Free Radicals; Glutathione; Male; Rats; Rats, Inbred Lew; Spinal Cord; Uric Acid; Vitamin E

I previously described that bowel tolerance (the amount that almost causes diarrhea) to oral ascorbic acid, increases in a person somewhat proportionally to the "toxicity" of his disease. Ascorbic acid ameliorates symptoms and sometimes cures certain diseases at high threshold levels near bowel tolerance. High concentrations of ascorbate cause the redox potential of the redox couple (ascorbate/dehydroascorbate, AA/DHA) to become reducing in diseased tissues. Allergic and sensitivity reactions are frequently ameliorated and sometimes completely blocked by massive doses of ascorbate. I now hypothesize that one mechanism in blocking of allergic symptoms is the reducing of the disulfide bonds between the chains in antibody molecules making their bonding antigen impossible. I further hypothesize that antibodies seek to match antigens only in areas where stray free radicals or a relatively oxidizing redox potential exists. The redox state of normal, healthy tissue does not allow for the bonding of antibodies to antigen. When antioxidant, free radical scavenging systems are overwhelmed, inflammatory, hypersensitivity, and "autoimmune" conditions may result.

Topics: Animals; Antigen-Antibody Reactions; Ascorbic Acid; Autoimmune Diseases; B-Lymphocytes; Biological Evolution; Disulfides; Drug Hypersensitivity; Food Hypersensitivity; Histamine H1 Antagonists; Humans; Hypersensitivity; Oxidation-Reduction; Pneumonia, Pneumocystis; Receptors, Antigen, T-Cell

Topics: Adjuvants, Immunologic; Animals; Ascorbic Acid; Autoimmune Diseases; Epididymis; Guinea Pigs; Immunization; Male; Nutrition Disorders; Orchitis; Skin Tests; Testis; Vegetables

Topics: Adult; Ascorbic Acid; Autoimmune Diseases; Ceruloplasmin; Chronic Disease; Copper; Diet; Humans; Male; Mathematics; Metabolism, Inborn Errors; Middle Aged; Schizophrenia; Time Factors