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)

Low-risk myelodysplastic syndrome (MDS) is characterized by cytopenia, mainly anemia, because of ineffective hematopoiesis. Some of the patients with ineffective erythropoiesis, with or without ring sideroblasts in their bone marrow, develop severe anemia requiring frequent blood transfusions and consequently develop iron overload. Excess free iron in cells catalyses the generation of reactive oxygen species (ROS) that cause cell and tissue damage. Using flow cytometry techniques, we compared the oxidative status of red blood cells (RBC), platelets and neutrophils in 14 MDS patients with those of normal donors. The results show that ROS were higher while reduced glutathione (GSH) was lower in their RBC and platelets compared with normal cells. In neutrophils, no difference was found in ROS, while the GSH levels were lower. A correlation (r = 0.6) was found between serum ferritin levels of the patients and the ROS in their RBC and platelets. The oxidative stress was ameliorated by a short incubation with the iron-chelators, the deferrioxamine and deferiprone or with antioxidants such as N-acetylcysteine, suggesting that MDS patients might benefit from treatment with iron-chelators and antioxidants.
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PMID:Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. 1797 87

A previously undescribed mutation of hereditary gamma-glutamylcysteine synthetase (GCS) deficiency was found in a 5 year old boy of Moroccan origin. He presented with chronic haemolytic anaemia, delayed psychomotor development and progressive motor sensitive neuropathy of lower extremities. The parents were third degree relatives. The activity of glycolytic enzymes were found to be normal in the propositus, his parents and a sister, but and a complete lack of GSH was found in the propositus. Accordingly, the measurement of de novo GSH synthetic enzymes was undertaken, and severe GCS deficiency was found in the propositus. Both parents and his sister presented GCS activity ranging from 69% to 90% of normal. GCS gene sequencing showed that the propositus was homozygous for a 1241C>T mutation in exon 11 and both parents and his sister were heterozygous. This mutation predicts a Pro414Leu amino acid substitution. Even though the homology between GCS and crystallographically solved, functionally related proteins is not very high, a three-dimensional model of GCS was derived using Modeller Software. GCS deficiency is a very rare autosomal recessive disorder reported so far in only 8 unrelated probands with severe haemolytic anaemia. In only 3 of these was the anaemia associated with severe neurological dysfunction. We report here the fourth case of GCS deficiency presenting neuropathy, giving further support to the eventual relationship between this enzymopathy and neurological damage.
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PMID:Chronic non-spherocytic hemolytic anemia associated with severe neurological disease due to gamma-glutamylcysteine synthetase deficiency in a patient of Moroccan origin. 1802 85

A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS approximately FA approximately XP>DS approximately AT approximately controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (< or =15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed.
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PMID:Different patterns of in vivo pro-oxidant states in a set of cancer- or aging-related genetic diseases. 1805 16

The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.
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PMID:The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. 1955 Dec 93

Oxidative damage of biomolecules and antioxidant status in erythrocytes of humans from an outbreak of argemone oil (AO) poisoning in Kannauj (India) and AO intoxicated experimental animals was investigated. Erythrocytes of the dropsy patients and AO treated rats were found to be more susceptible to 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) induced peroxidative stress. Significant decrease in RBC glutathione (GSH) levels (46, 63%) with concomitant enhancement in oxidized glutathione (172, 154%) levels was noticed in patients and AO intoxicated animals. Further, depletion of glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G-6-PDH) and glutathione-S-transferase (GST) (42-52%) was observed in dropsy patients. Oxidation of erythrocyte membrane lipids and proteins was increased (120-144%) in patients and AO treated animals (112-137%) along with 8-OHdG levels in whole blood (180%) of dropsy patients. A significant reduction in alpha-tocopherol content (68%) was noticed in erythrocytes of dropsy patients and hepatic, plasma and RBCs of AO treated rats (59-70%) thereby indicating the diminished antioxidant potential to scavenge free radicals or the limited transport of alpha-tocopherol from liver to RBCs leading to enhanced oxidation of lipids and proteins in erythrocytes. These studies implicate an important role of erythrocyte degradation in production of anemia and breathlessness in epidemic dropsy.
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PMID:Antioxidant status of erythrocytes and their response to oxidative challenge in humans with argemone oil poisoning. 1842 7

Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to benzene or toluene alone suggests that, at the doses used in this study, toluene can enhance benzene-induced clastogenic or aneugenic bone marrow injury. These findings exemplify the importance of studying the effects of binary chemical interactions in animals exposed to lower exposure concentrations of benzene and toluene on benzene metabolism and clastogenicity. The relevance of these data on interactions for humans exposed at low benzene concentrations can be best assessed only when the mechanism of interaction is understood at a quantitative level and incorporated within a biologically based modeling framework.
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PMID:Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice. 1845 11

Methyldopa is used for treatment of hypertension in pregnancy. Side effects of methyldopa include anemia, which could result from decreased formation or accelerated death of circulating erythrocytes. Several drugs cause anemia by triggering of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling, the latter leading to phosphatidylserine exposure at the erythrocyte surface. Stimulators of erythrocyte membrane scrambling include increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) and ceramide. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study explored whether eryptosis could be triggered by methyldopa. Erythrocytes from healthy volunteers were exposed to methyldopa, and phosphatidylserine exposure (annexin A5 binding), cell volume (forward scatter), [Ca(2+)](i) (Fluo3-dependent fluorescence), and ceramide formation (anti-ceramide-fluorescein isothiocyanate antibody) were determined by flow cytometry. Methyldopa (6 microg/ml) did not increase [Ca(2+)](i) but led to stimulation of ceramide formation resulting in significant phosphatidylserine exposure and, at higher concentrations, to cell shrinkage. Methyldopa further decreased the GSH/GSSG ratio, pointing to oxidative stress. The scavenger N-acetyl-L-cysteine significantly blunted methyldopa-induced eryptosis. Clearance of erythrocytes from circulating blood was significantly accelerated by treatment with methyldopa. The present observations disclose a novel action of methyldopa, which may well contribute to drug-induced anemia.
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PMID:Stimulation of erythrocyte cell membrane scrambling by methyldopa. 1877 3

The puffer fish Lagocephalus lagocephalus represents serious public health problems in the world. The relative toxicity of each organ (liver and flesh) was determined by the relation dose-death time "mouse bioassay." The average liver toxicity of the puffer fish was the highest when compared with flesh giving 14.32 and 10.88 MU/g, respectively. A mouse unit is the amount of toxin (extract of fish organ) that kills a 20 g male mouse in 30 min after intraperitoneal injection. One mouse unit is equivalent to 0.22 microg of TTX. For the rat bioassay tests, Wistar rats were daily i.p. injected, for 10 d, with extracts of liver (LT) or flesh (FT) (muscles + skin) of L. lagocephalus. Control rats received injection of NaCl (0.9%). During the experiment, a significant reduction in red blood cell number (RBC), hemoglobin (HGB) concentration, and hematocrit (HCT) was observed essentially after 10 d of treatment in the FT and LT-exposed groups. Consequently, treatment led to severe anemia and hemolytic action as indicated by a significant reduction in the total number of erythrocytes. In fact, our study revealed a significant increase in erythrocyte lipid peroxidation (LPO) in FT and LT groups compared with controls after experimental exposure. The flesh and liver tissue extracts also altered antioxidative enzymes activities: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Histopathological alterations in the spleen occurred exclusively at the end of treatment. We marked also an increase in reticulo-endothelial cells, which led to remove damaged erythrocytes.
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PMID:Hematological toxicity associated with tissue extract from poisonous fish Lagocephalus lagocephalus--influence on erythrocyte function in Wistar rats. 1880 10

The present study was designed to evaluate the effect of a new iron tonic (squid ink melanin-Fe [SM-Fe]) on remission of iron deficiency anemia (IDA) using a rat model of IDA. The rat IDA model was established with low-iron diet feeding and caudal vein blooding. Then different dosages of SM-Fe were given to the rats once a day by intragastric administration, with FeSO4 and FeCl3 as positive control. The content of Hemoglobin (Hb), red blood cell (RBC), hematocrit (HCT), and mean corpuscular volume (MCV) were analyzed in addition to the contents of serum iron (SI) and intracellular free erythrocyte protoporphyrin (FEP). The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum was also measured. The results showed that anemia caused by iron deficiency was established as a consequence of the low-iron diets. SM-Fe showed an effective restoration action by returning Hb, RBC, HCT, MCV, SI, and FEP in IDA animals to normal values. An antioxidant effect was also observed that reduced MDA level, enhanced the activities of SOD and GSH-Px in serum, and protected erythrocytes from the injury of reactive oxygen species as a consequence of SM-Fe intake. In comparison with FeSO4 and FeCl3, higher bioavailability of iron and fewer side effects were also observed. In conclusion, SM-Fe remitted iron deficiency anemia symptoms significantly, suggesting that SM-Fe might contribute to improving hemopoietic function in IDA rats and might be exploited as a safe, efficient new iron tonic.
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PMID:Effect of squid ink melanin-Fe on iron deficiency anemia remission. 1901 17

This study was carried out on 68 Theileria annulata naturally infected buffaloes in addition to 25 parasitologically free buffaloes distributed in small herds at Dakahlia and Gharbya governorates, Egypt, to demonstrate the clinical picture associated with theileriosis in this buffaloes with particular emphasis to the oxidative stress and ketosis relationship. Clinical signs recorded in infected buffaloes were in the form of fever, enlargement of one or more lymph node, ocular discharge, corneal opacity, skin lesions, decreased milk yield, pale mucous membrane and anorexia. Blood and serum analysis revealed significant (p<or=0.05) decrease in RBCS and or Hb concentration in infected animals compared to control ones. Moreover, significant increase (p<or=0.05) in the levels of beta hydroxy butyric acid (BHBA) and non-esterified free fatty acid (NEFA) with a significant decrease (p<or=0.05) in the levels of reduced glutathione (R.GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), nitric oxide (NO), glucose and glucose-6-phosphate dehydrogenase (G6PD) in infected animals compared to control ones. It can be concluded that T. annulata plays an important role in the occurrence of anemia, oxidative and ketotic stressor in Egyptian water buffaloes.
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PMID:Clinical and biochemical studies on Theileria annulata in Egyptian buffaloes (Bubalus bubalis) with particular orientation to oxidative stress and ketosis relationship. 1955 34


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