Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.
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PMID:Oxygen radicals in ulcerative colitis. 135 59

This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.
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PMID:Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment. 143 53

We measured superoxide scavenging activity (SSA) of erythrocytes with the recently developed chemiluminescence method by Nakano et al in Down syndrome and various hematological diseases. Hematological disorders were aplastic anemia, myelodysplastic syndrome, multiple myeloma, malignant lymphoma and chronic myelogenous leukemia. The SSA of erythrocytes was 1.7 times higher in Down syndrome, which was consistent with values reported in the previous publications. The erythrocyte SSA in patients of multiple myeloma treated with interferon-alpha was higher than that in healthy volunteers. The erythrocyte SSA in myelodysplastic syndrome, malignant lymphoma and chronic myelogenous leukemia did not differ from that in healthy volunteers. The mean value of erythrocyte SSA in aplastic anemia also remained within normal range. However, when an individual's hemoglobin concentration was compared with his or her own erythrocyte SSA, there was a clear correlation between them. Namely erythrocyte SSA increased when anemia was severe. There was no correlation between erythrocyte SOD activity and ageing.
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PMID:Erythrocyte superoxide dismutase in various hematological diseases. 215 34

The present study was designed to investigate the effects of nickel chloride on dietary iron deficiency in rats. The degree of iron deficiency was relatively moderate, but a more generalized anemia occurred in iron deficiency, in absence of nickel chloride. Moderate iron deficiency anemia induced increased lactate-dehydrogenase activity of serum and bone marrow, perhaps related to the decreased production of energy by oxidative means. Nickel chloride, perhaps for its ability to change iron absorption, for the maintenance of bone marrow metabolism and for to increase ceruloplasmin activity, inhibited the alteration on hemoglobin synthesis. Furthermore, nickel chloride possibly for its action on copper content and Cu-Zn superoxide-dismutase activity, inhibits the shortening of the red cell life span, caused by superoxide radicals.
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PMID:Influence of nickel chloride on iron-deficiency in rats. 263 91

Several observations in the recent literature have indicated that Fanconi anemia (FA) cells may be primarily deficient in the detoxification of activated oxygen species. To evaluate the antioxidant status of FA fibroblasts, we measured Mn-containing superoxide dismutase (Mn-SOD), CuZn-containing superoxide dismutase (CuZn-SOD), catalase, and glutathione peroxidase activities, as well as cellular glutathione contents and total nonenzymatic antioxidant potential in FA and control fibroblasts at multiple time points during a single passage. All parameters exhibited a characteristic pattern of changes during a period of 19 days following trypsinization. Unlike FA erythrocytes, which are known to be deficient in CuZn-SOD, FA fibroblasts exhibited normal CuZn-SOD activities. Also, the nonenzymatic "antioxidant potential" as well as glutathione levels were similar in FA and control fibroblasts. However, Mn-SOD, catalase, and glutathione peroxidase activities were consistently higher in FA fibroblasts. We hypothesize that the elevation of these enzyme activities might reflect a cellular "prooxidant" state in FA resulting from an increased formation of endogenous oxidizing molecular species that trigger enhanced synthesis of certain enzymatic antioxidant defenses.
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PMID:Antioxidant status of Fanconi anemia fibroblasts. 362 59

1. The progression of Heinz body anaemia was studied in groups of lambs of low- and high-copper status, produced through breeding or Cu supplementation, when they were transferred from improved pasture to rape (Brassica napus L.) in autumn. Some lambs had previously received selenium by injection. The Cu and Se supplements markedly increased superoxide dismutase (EC 1.15.1.1; SOD) and glutathione peroxidase (EC 1.11.1.9; GSHPx) activities respectively in the erythrocytes, and both supplements had elicited growth responses at pasture. 2. At the time of transfer to rape, lambs not treated with Cu had lower whole-blood haemoglobin (Hb) concentrations and a higher percentage of erythrocytes containing Heinz bodies (6.6 v. 3.7%, P less than 0.01) than Cu-treated lambs: the corresponding effects of Se treatment were similar in direction but lower in magnitude (P less than 0.05). 3. After grazing rape for 2 weeks the mean Hb concentration had fallen by 30 g/l while Heinz body count had increased from 5 to 25%. However, counts were negatively correlated with the initial values and were unaffected by the Cu and Se treatments which maintained high plasma Cu concentrations and SOD and GSHPx activities. 4. The results provide the first evidence that Cu deficiency can induce Heinz body formation and the anaemia in grazing Cu-deficient lambs may be partly haemolytic in origin. The concomitant Se deficiency added marginally to the problem but neither the separate nor combined deficiencies increased the susceptibility of lambs to brassica anaemia.
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PMID:Heinz body anaemia in lambs with deficiencies of copper or selenium. 368 53

Experiments were conducted in copper deficient male and female rats fed diets containing fructose or starch in order to determine whether the same type of interaction between copper status and dietary carbohydrate found in male rats also occurs in the female rat. Mortality occurred only in the male rats fed the fructose diet deficient in copper with 40% of the animals dying during the 8 week study. Only anemia, hypercholesterolemia, increased BUN, heart hypertrophy and reduced body weight were observed in these animals which could be related to their mortality. Despite the increased mortality, plasma ceruloplasmin, erythrocyte SOD and hepatic copper concentrations were reduced to a similar extent in all rats regardless of the sex of the animals or of the type of dietary carbohydrate fed. The results of the present study indicate that although direct measurements of copper status of female rats fed fructose diet deficient in copper are similar to their male counterpart, they are apparently protected from the lethal consequences of the deficiency.
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PMID:Female rats are protected against the fructose induced mortality of copper deficiency. 374 32

Liposomal-encapsulated superoxide dismutase was clinically applied to patient showing an increase in neutrophil active oxygen generation, and those with diseases such as severe rheumatoid arthritis (RA), Crohn's disease and progressive systemic sclerosis (PSS) in which presence of a plasmatic clastogenic factor has been demonstrated. Liposomal SOD injection (2.5 mg twice a week) resulted in marked remission in 12 out of 16 patients with active Behcet's disease. The drug was impressively effective on patients with intestinal Behcet. Remission rates in the other diseases was 7 out of 8 mucocutaneous lymphnode syndrome (MCLS, Kawasaki disease) 3 out of 5 dermatitis herpetiformis, IgA linear bullous dermatosis or severe cement dermatitis, 4 out of 9 active and severe RA, 3 out of 3 PSS, 4 out of 4 Crohn's disease, 3 out of 4 colitis ulcerosa, and 2 out of 2 unresponsive (hemolytic) anemia. To be emphasized was that three severe active RA patients and two terminal-stage PSS patients with dyspnea due to lung fibrosis showed dramatic improvement after administration of liposomal SOD. In addition, in 13 out of 15 malignant neo plastic patients including cancer, malignant lymphoma and leucemia who were receiving radiotherapy (total dose, more than 4000 rads) and chemotherapy including anthracycline analogs (total over 450 mg/m2) and bleomycin, the drug also prevented the appearance of myocardiac injury and fibrosis, sometimes seen as a consequence of chemotherapy. Liposomal SOD, which shows no toxicity, has various advantages compared to free SOD preparations, and is highly and broadly applicable to various clinical disorders.
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PMID:Effect of liposomal-encapsulated superoxide dismutase on active oxygen-related human disorders. A preliminary study. 388 Feb 79

The essentially of copper for normal fetal and neonatal development has been well documented, although copper metabolism during this period is poorly understood. The dietary requirement for copper is influenced by genetic background. The neurological phenotypic characteristics of the mutant gene quaking (qk) in mice resemble in part those of copper-deficient animals. Supplementation of the maternal diet with copper during pregnancy and lactation, or during lactation alone, greatly reduced the frequency of tremors characteristic of these mutants, and brought the otherwise low copper concentrations in the brain to normal. Prenatal copper supplementation of crinkled (cr) mice increased neonatal survival and produced nearly normal development of skin and hair. Non-supplemented cr/cr mice showed anaemia at 21 days of age which disappeared later. Similarly, copper concentration in liver and hair was low in young but normal in old cr/cr mice. However, activity of copper--zinc-superoxide dismutase (Cu-ZnSOD) remained low even at 60 days of age. Copper supplementation brought both SOD activity and copper concentration of liver and hair to normal. The errors in copper metabolism produced by qk and cr appear to be expressed at different periods of development. The hypothesis that there are rapid changes in the metabolism of copper is supported by the observation that molecular distribution of copper in rat intestine changes drastically during the neonatal period.
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PMID:Copper in fetal and neonatal development. 690 85

Lipid peroxidation as shown by malonic dialdehyde (MDA) levels and enzymic antioxidant defense systems were evaluated in red cells from patients with renal affections free of chronic renal failure (group 1), in conservative curable stage of chronic renal failure (group 2a), in terminal stage nondialysis patients (group 2b) and in healthy donors. MDA was higher in patients, in group 2b in particular. MDA levels correlated with concentrations of endogenic creatinine in the serum. Catalase and glutathione peroxidase were at control levels. SOD was not changed in group 1 but appeared reduced in other groups. Its activity was not related to serum creatinine. An inverse relationship existed between MDA content and SOD activity in red cells. It is believed that progression of chronic renal insufficiency leads to activation of lipid peroxidation and deterioration of antioxidant defense in red cells contributing to more active red cell destruction causing anemia in uremia.
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PMID:[The erythrocyte pro-oxidant and antioxidant systems of patients with chronic kidney failure]. 748 45


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