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)

Intravenous administration of lead acetate to rabbits for 10 weeks at 2 week intervals resulted in significantly elevated blood lead levels, slight anemia with marked microspherocytosis and moderate basophilic stippling, and marked depression of red cell delta-aminolevulinic acid (ALA) dehydratase activity. However the decrease in red cell pyrimidine 5'-nucleotidase (P5N) activity was slight when compared to the red cell P5N activity of comparable reticulocyte-rich blood, and intracellular accumulation of pyrimidine nucleotides could not be demonstrated. In the in vitro inhibition test the same degree of inhibition of red cell P5N activity seen in hereditary red cell P5N deficiency was obtained by using a lead concentration 200--400 times higher than the lead levels detected in human plumbism. Most importantly, there were no differences in the lead-induced inhibition of human and rabbit red cell P5N. From the results of the in vitro inhibition test, lead-induced red cell P5N deficiency appears to be one of several pathogenic mechanisms in chronic lead exposure associated with the accumulation of lead in bone marrow. A decrease in rec cell P5N activity could not be demonstrated despite the marked depression in red cell ALA dehydratase activity, and slight anemia with marked microspherocytosis and moderate basophilic stippling in this experiment. These results suggest that lead affects red cells at multiple metabolic loci.
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PMID:A role of red cell pyrimidine 5'-nucleotidase in experimental lead poisoning. 23 20

Blood-lead level (Pb-B), erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, delta-aminolevulinic acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10-13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10-40 mug/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a significant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children larger than or equal to women greater than men. Based on the FEP response, it is proposed that 25 mug Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.
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PMID:Impact of air pollution by lead on the heme biosynthetic pathway in school-age children. 99 44

Three groups of rabbits (A, B, and C; 6 rabbits/group) were fed a lead supplement of 25, 50, and 100 mg of Pb/kg of live weight/day for 87 days to compare the efficacies of 3 diagnostic tests--whole blood lead concentration, urinary delta-aminolevulinic acid (UALA), and fluorescent erythrocyte test (FET)--and to determine the clinicopathologic changes of experimentally induced lead poisoning in rabbits. All rabbits given lead had whole-blood lead concentrations greater then the maximum value (0.030 mg/dl) for control rabbits (group D), indicating that this measurement is a reliable indicator of lead ingestion. All group A rabbits (fed 25 mg of Pb/kg) and 66% negative UALA test results, with values less than the maximum value (0.12 mg/dl) for group D (control) rabbits. Only group C rabbits (fed 100 mg of Pb/kg) had consistently positive UALA FINDINGS. The test was therefore considered unreliable for detecting daily lead intakes less than 100 mg/kg of live weight of rabbits. All rabbits given lead had erythrocytes which fluoresced red when exposed to light rays with wavelenghts from 320 to 400 nm; fluorescence was not observed in erythrocytes of control rabbits. The FET appears to be a convenient and reliable diagnostic test for lead ingestion. In groups B and C, clinical signs of lead poisoning were mild, nonpersistent anemia characterized by the presence of poikilocytes, hupochromic erythrocytes, target cells, erythroblasts, erythrocytes with punctate basophilic stippling, reduced mean corpuscular hemoglobin concentrations, and relative lymphocytosis, neutropenia, and eosinopenia. One rabbit from the group fed the largest dose displayed partial anorexia.
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PMID:Chronic plumbism in rabbits: a comparison of three diagnostic tests. 115 38

The intraperitoneal administration of Pb acetate (5 x 20 mg Pb/kg per day) evokes a moderate and transient hypochromic anemia, a long-lasting enhanced urinary excretion of delta-aminolevulinic acid whereas the urinary excretion of alkaline phosphatase is not affected and that of lactic dehydrogenase only marginally. It is concluded that neither the hematologic response nor the slight nephrotoxicity are responsible for the lethal action of Pb. Chelate treatment started 3 days after the last Pb dose and was continued over 7 weeks. The daily intraperitoneal dose was 25, 50, and 100 mumol/kg, respectively. The efficacy in promoting the urinary excretion of Pb decreased in the following order: Ca diethylenetriaminepentaacetate greater than 2,3-dimercaptopropane-1-sulfonate greater than Zn diethylenetriaminepentaacetate greater than D-penicillamine. This effect was mainly due to the mobilization of skeletal Pb. The chelating agents also lowered the excretion of delta-aminolevulinic acid but failed to exert a beneficial influence on the anemia and the lethal action of Pb. These negative results raise questions about the usefulness of chelation therapy in cases of acute Pb poisoning.
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PMID:Influence of chelation therapy on acute lead intoxication in rats. 124 21

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.
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PMID:Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism. 231 47

The hemin regulation of L-alanine:4,5-dioxovalerate transaminase, the enzyme proposed for an alternate route of delta-aminolevulinic acid (ALA) biosynthesis in mammalian system was studied in different conditions: phenylhydrazine induced anemia, polycythemia by erythropoietin to anemic rats, treatment with cobalt chloride, a porphyrogenic drug. The activity of L- alanine:4,5-dioxovalerate transaminase in liver and kidney is stimulated in phenylhydrazine, whereas, erythropoietin injection to anemic rats prevents such stimulation. Further treatment with cobalt chloride to erythropoietin treated anemic rats stimulates the enzyme activity. Actinomycin D, however, inhibits the stimulation of L-alanine:4,5-dioxovalerate transaminase by phenylhydrazine suggesting that induction is at the level of transcription. Induced level of this enzyme in anemic condition was estimated quantitatively by radial immunodiffusion using antibody raised against L-alanine:4,5-dioxovalerate transaminase. Moreover, our studies reveal that stimulation of L-alanine:4,5-dioxovalerate transaminase in anemic condition is dependent on depletion of heme level. The regulatory role of intracellular heme pool on the induction of this enzyme suggests its physiological importance in heme biosynthesis.
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PMID:Induction of L-alanine:4,5-dioxovalerate transaminase by phenylhydrazine is associated with depletion of heme level. 309 Oct 22

5-Aminolaevulinic acid (ALA) synthase activity was measured in highly purified preparations of age-matched human erythroblasts. Enzyme activity in immature normoblasts was four-fold higher than that found in late orthochromatic normoblasts. ALA synthase activity in the immature erythroblasts in primary acquired sideroblastic anaemia (PASA) was reduced and remained unchanged during further erythroid differentiation. The pattern of erythroblast ALA synthase activity in two patients with congenital dyserythropoietic anaemia (CDA) and in one patient with beta-thalassaemia intermedia was similar to that found in PASA. This study has clearly demonstrated reduced erythroblast ALA synthase activity in PASA but has also found reduced enzyme activity in conditions in which ring sideroblasts are not prominent. This would suggest that haem synthesis is abnormal in PASA but that reduced erythroblast ALA synthase activity does not inevitably lead to ring sideroblast formation.
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PMID:5-Aminolaevulinic acid synthase activity in developing human erythroblasts. 339 Mar 96

The possible effect of cisplatin on porphyrin metabolism was studied in 25 patients with various malignancies treated with high-dose cis-diamminedichloroplatinum. Haematocrit, red blood cells, haemoglobin, white blood cells, platelets and reticulocytes together with coproporphyrin and protoporphyrin in red blood cells were determined before each course of chemotherapy in all patients. In addition, coproporphyrin, uroporphyrin, delta-aminolevulinic acid, and porphobilinogen were determined in the urine just before and 24 h after each course of treatment. Cisplatin administration was followed by a significant suppression of coproporphyrin and protoporphyrin in red blood cells and coproporphyrin, uroporphyrin, delta-aminolevulinic acid and porphobilinogen in urine. The changes observed paralleled similar changes in haematocrit, red blood cells and haemoglobin, strongly suggesting that cisplatin-induced anaemia may be due to a blocking effect of the drug affecting one or more enzymatic steps in the biosynthesis of porphyrins and haem. A moderate fall in the white blood cell count and a mild fall in platelets together with a steady increase of reticulocytes were also observed during treatment.
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PMID:Adverse effect of cis-diamminedichloroplatinum II (CDDP) on porphyrin metabolism in man. 371 97

In a study of the urinary excretion of haem precursors in patients with rheumatoid arthritis, iron-deficiency anaemia, and in healthy controls, certain differences were found. In iron-deficiency anaemia the excretion of both porphobilinogen and delta-aminolevulinic acid was increased, whereas in patients with rheumatoid arthritis only the porphobilinogen excretion was increased.A further study on the erythrocyte activity of delta-aminolevulinic acid dehydrase showed a higher activity in the erythrocytes from patients with rheumatoid arthritis compared with healthy controls.
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PMID:Haem biosynthesis studied in patients with rheumatoid arthritis. 501 45

We have studied the effect of lead on the fluidity of erythrocyte membrane to clarify if lead can interact in vivo with biological membranes. Erythrocyte membranes were chosen in our study because a decrease of red cell osmotic fragility is also evident in the absence of laboratory and clinical signs of anaemia. The study was undertaken using the Electron Spin Resonance technique with two spin labels 5-doxyl stearate and 16-doxyl-stearate, which probe the physical state of the polar surface and the inner core of the membrane respectively. Red blood cells and erythrocyte ghosts were prepared from the blood of workers occupationally exposed to lead and from healthy controls. The determinations of Pb blood, Pb urine, urine coproporphyrin and delta-aminolevulinic acid showed an increased internal dose of lead, but the ordinary metabolic and haematological parameters were in the normal range. Our results show that in lead workers there is a change in chemical physical state both in erythrocytes and erythrocyte ghosts consistent with a decrease of membrane fluidity, which is evident in the surface as well as in the inner core of the membrane. The degree of membrane fluidity modification does not appear correlated with blood lead level. Changes in the membrane structural organization could be the molecular basis of some pathological alterations induced by lead.
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PMID:Changes of membrane fluidity in erythrocytes of lead-exposed workers. 629 13


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