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)

Methylethyl ketoxime (CAS No. 96-29-7; MEKO; 2-butanone oxime), an antioxidant agent used in paints, resins, and adhesives, was tested for reproductive toxicity in a two-generation study with CD (Sprague-Dawley) rats. Thirty-eight-week-old rats/sex/group (F0) were administered MEKO in water, by gavage, at 0, 10, 100, or 200 mg/kg/day (at a dosing volume of 2 ml/kg), 5 days/week for 10 weeks with vaginal cytology evaluation (VCE) of F0 females during the last 3 weeks of the prebreed period. Animals were mated within groups for 3 weeks with dosing during mating, gestation, and lactation for 7 days/week. F0 parents and F1 weanlings, 10/sex/dose, were necropsied (after a 2-week postwean VCE in F0 females) with hematologic evaluation (including methemoglobin) and histology of adult livers, spleens, and reproductive organs. F1 weanlings, 30/sex/dose, were dosed for 11 weeks and mated as described above. Because of poor reproductive performance, not treatment related, F1 animals with no F2a litters were rebred to produce F2b litters. F1 parents and F2a weanlings, 10/sex/dose, were necropsied and evaluated as described above. Inguinal mammary glands were examined histologically from all nonselected F1 and F2 (a and b) female weanlings. Adult toxicity was observed in both generations and both sexes at all doses. Treatment-related parental deaths occurred at 200 mg/kg/day. At 100 and 200 mg/kg/day, parents exhibited dose-related reduced body weights and weight gains, reduced feed consumption, clinical signs of toxicity, and anemia with concomitant extramedullary hematopoiesis and hemosiderosis in livers and spleens (and increased spleen weights). At 10 mg/kg/day, only adult liver and spleen histologic effects were present. There was no evidence of reproductive organ or mammary glad pathology or of reproductive or postnatal toxicity at any dose tested. There was no adult "no observable adverse effect level" (NOAEL) established; the NOAEL for reproductive and postnatal toxicity was at least 200 mg/kg/day for rats in this study.
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PMID:Reproductive toxicity evaluation of methylethyl ketoxime by gavage in CD rats. 878 80

A previous study revealed that DQ-2511, a new gastroprokinetic drug, induced hemolytic anemia together with increased Heinz body formation, preceded by a marked decrease in erythrocyte reduced glutathione (GSH) content, after 2 weeks of dosing onward in dogs. In this study, the effect of DQ-2511 on erythrocytes in the early period of dosing, in comparison with that of beta-acetylphenylhydrazine (APHZ), was investigated to confirm the difference between this drug and APHZ in the mechanism of increased Heinz body formation. DQ-2511 and APHZ were administered orally to beagle dogs for 1 week at dose levels of 600 and 4 mg/ kg, respectively. Dogs receiving APHZ showed anemia after dosing for 7 days, together with an increase in methemoglobin and Heinz body formation after 3 days of dosing. In contrast, blood GSH, glutathione reductase, and gamma-glutamylcysteine synthetase were only slightly decreased after dosing for 7 days. In dogs treated with DQ-2511, erythrocyte GSH began to decrease after 1 day of treatment and was about 25% of the control value after 7 days; however, no changes were seen in blood glutathione reductase, GSH peroxidase, or gamma-glutamylcysteine synthetase level. Hepatic GSH was decreased slightly. In another experiment, SD rats were administered DQ-2511 and APHZ orally for 1 week at dose levels of 1600 and 15 mg/kg, respectively. Rats receiving DQ-2511 showed no anemia or any changes in erythrocyte GSH and Heinz body formation. In contrast, rats treated with APHZ showed a marked anemia and increases in Heinz body formation and erythrocyte GSH. These results demonstrate that DQ-2511 causes a marked decrease in GSH in dogs, resulting in Heinz body anemia, whereas APHZ induces Heinz body formation after a significant increase in methemoglobin, and suggest that impairment of the GSH redox cycle and synthetases of GSH are not involved in the decreased GSH after DQ-2511 treatment. This difference in effects on GSH content may indicate the existence of a species difference in the anemia induced by DQ-2511.
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PMID:A possible mechanism of heinz body hemolytic anemia induced by DQ-2511, a new gastroprokinetic drug, in dogs. 892 30

Twenty subjects--patients with anemia and their close relatives representing 7 families, were tested for thalassemia. Heterozygotic beta-thalassemia was detected in 17 cases. The national composition of this patient population was as follows: 7 Pathans (Afghanistan), 1 family; 2 Armenians (Georgia), mother and son; 2 Tajiks, sibs; 2 patients of mixed Russian-Ukrainian-Polish-Azerbaijan origin, mother and son; 1 Russian-Arab child and his Arab father (Syria); 1 Uzbek woman and 1 Russian child. The mean content of Hb in the blood for patients with heterozygotic beta-thalassemia is 110 +/- 3.8 g/liter, that of HbA2 fraction 4.8 +/- 0.26% and of HbF fraction 2.6 +/- 0.39%. Clinical manifestations of the disease varied, being more grave in children than in adults. In an Armenian family from Batumi thalassemia minor was diagnosed in the mother and son, whereas in the father and other son a periodic disease was revealed. In a family of 7 members from Afghanistan thalassemia minor was found in 4 representing the paternal line, minimal thalassemia was suspected in 3, and a deficiency of glucose-6-phosphate dehydrogenase in red blood cells was revealed in 5: in the mother and 4 children. No increase of methemoglobin level was revealed in either of the examinees.
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PMID:[Beta-thalassemia and glucose-6-phosphate dehydrogenase deficiency]. 904 21

Two major causes of the anemia in beta-thalassemia are a deficiency in hemoglobin (Hb) beta-subunit (and consequently HbA) synthesis and, due to the resulting excess of Hb alpha-subunits, erythroid cell hemolysis. The hemolytic component might be ameliorated by increasing the intracellular proteolysis of the excess alpha-subunits. Isolated 3H-labeled alpha-chains are known to be degraded primarily by the adenosine triphosphate (ATP)- and ubiquitin (Ub)-dependent proteolysis pathway in unfractionated beta-thalassemic hemolysates. Our objective was to increase this degradation by targeted intervention. Ub aldehyde (Ubal), a synthetic inhibitor of isopeptidases (proteases that hydrolyze the bond between the Ub polypeptide and its protein adduct), was added to reaction mixtures containing a hemolysate from the blood cells of one of four beta-thalassemic donors and 3H-alpha-chains or 3H-alpha-globin as a substrate. Optimum enhancement of ATP-dependent degradation occurred at 0.4 to 1.5 micromol/L Ubal and ranged from 29% to 115% for 3H-alpha-chains and 47% to 96% for 3H-alpha-globin among the four hemolysates. We suggest that Ubal stimulates 3H-alpha-subunit proteolysis by inhibition of an isopeptidase(s) that deubiquitinates, or "edits," Ub-3H-alpha-subunit conjugates, intermediates in the degradative pathway. In control studies, similarly low Ubal concentrations did not enhance the degradation of 3H-alpha2beta2 (HbA) tetramers or inhibit the activities of methemoglobin reductase and four selected glycolysis pathway enzymes. These and other results may be the basis for a therapeutic approach to beta-thalassemia.
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PMID:Ubiquitin aldehyde increases adenosine triphosphate-dependent proteolysis of hemoglobin alpha-subunits in beta-thalassemic hemolysates. 924 65

Hematological investigation of an antenatal patient led to the identification of a new beta-thalassemia mutation involving the net insertion of eight nucleotides into exon 2 of the beta-globin gene. As a result of the shift in the protein reading frame, this gene codes for an elongated beta-globin chain (159 amino acids) with an abnormal amino acid sequence beyond residue beta 99. There is no evidence of any abnormal hemoglobin in the circulation. The patient has a mild form of beta-thalassemia intermedia with moderate anemia, evidence of iron overload, severe red cell morphological changes, a significant reticulocytosis, and a marked increase in the proportion of fetal hemoglobin.
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PMID:Mild thalassemia intermedia resulting from a new insertion/frameshift mutation in the beta-globin gene. 941 43

Duodenal iron absorption from food is selectively blocked to prevent iron intoxication. The prime example of pathologic increase in intestinal iron absorption is seen in patients with hemochromatosis. They suffer iron damage to the heart, liver, and other tissues resulting in premature death if the iron is not removed by vigorous phlebotomy. Examples of overcoming the intestinal barrier to iron are alcohol consumption, vitamin preparations with vitamin C, and iron consumed by individuals without anemia. Endogenous generation of excess iron by hemolysis, owing to abnormal hemoglobin or many transfusions, are not controlled by the intestinal barrier.
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PMID:Understanding iron absorption and metabolism, aided by studies of hemochromatosis. 951 82

Dapsone (4,4'diaminodiphenyl-sulphone) commonly used in the treatment of patients who suffer from leprosy, is a strongly oxidative drug, producing damage to the red cell membrane. This study investigated whether Vitamin E would have a protective effect on the red cell membrane from oxidant damage caused by Dapsone in patients with leprosy. We have studied 16 patients for 4 months, divided into two groups. Group 1 (n = 7) dapsone (DDS): 100 mg/day; Group 2 (n = 9) dapsone: 100 mg/day in addition with Vitamin E: 800 U/day. We did not include patients with low levels of Glucose-6-Phosphate Dehydrogenase (G-6-PD) because of their sensibility to this drug. At the beginning of the treatment we determined the level of G-6-PD. All patients showed a normocytic normochromic anemia with a decrease in Haptoglobine levels (below 5 mg/dl). Statistical analyses showed that reticulocyte counts did not present significant differences between groups all through evolution. As for methemoglobin (Hi) we observed in Group 1 an increase between the first and the fourth month, which was not seen in group 2. Statistical analyses of the results suggest that oral Vitamin E confers partial protective effect and does not correct the hemolysis parameters produced by Dapsone treatment except for Hi levels which were more sensitive to the oxidant damage.
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PMID:[Vitamin E as protective agent against hemolysis in leprosy patients under dapsone treatment]. 953 24

Twelve patients with anemias and their close relatives were examined: 8 adults (3 men and 5 women) and 4 children (3 boys and 1 girl). Six of them were Armenians, 1 woman was Russian, and the rest were of mixed origin: 3 Russian-Azerbaijan-Ukrainian, 1 child Russian-Ukrainian-African, and 1 woman Russian-Ukrainian. Hemoglobinopathies were detected in 10 subjects from 4 families (3 families from Donetsk and 1 from Moscow). Homozygotic beta-thalassemia major (Hb F 98.9%) was diagnosed in a 2-year-old Armenian girl from Donetsk. The girl lags behind in development and suffers from anemia with hepatosplenomegaly and jaundice. Heterozygotic beta-thalassemia minor with increased levels of Hb A2 and Hb F was diagnosed in her parents (Armenians from Azerbaijan). A 15-year-old Russian-Azerbaijan-Ukrainian boy from another family in Donetsk had beta-thalassemia with HbD (94%). The boy suffers from anemia with hepatosplenomegaly, jaundice, and chronic hepatitis. Heterozygotic beta-thalassemia with increased levels of Hb A2 and Hb F was revealed in proband's mother and brother; the father was not examined. alpha-Thalassemia is suspected in a 3-year-old boy from a Russian-Ukrainian-African family in Donetsk; he presented with a very small "fast" abnormal hemoglobin fraction. The boy suffers from anemia with splenomegaly and systolic murmur. Blurred form of thalassemia minor is diagnosed in the mother. The father, an African from Zaire, was not examined. Heterozygotic beta-thalassemia with increased Hb A2 level was revealed in a 20-year-old Armenian boy from Moscow. He presented with manifest splenomegaly, chronic gastritis, and mitral valve prolapse. His mother suffers from thalassemia minor, was anemic during pregnancy, and there are cases of anemia in the family. No hematologic disorders were found in the father. No hemoglobinopathies were detected in a 59-year-old Russian women from the town of Tver with very grave anemia; apparently, her condition was acquired, but not hereditary. Data on patients in the city of Donetsk are of special interest, for there are virtually no reports about hemoglobinopathies in the Ukraine.
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PMID:[Beta-thalassemia and Hb D in patients with anemia]. 957 28

HbOThrace is an abnormal hemoglobin which is constructed by defective beta chains (Glu121-->Lys121). It mostly characterises the Muslim minority of the Thrace region. During the last 6 years, our department detected HbOThrace in 118 cases. Four groups were formed, the first consisted of cases of HbOThrace trait with normal iron and ferritin levels, the second of cases of HbOThrace hemoglobinopathy, the third of cases of HbOThrace/Hb beta zero hemoglobinopathy and the fourth of cases of HbOThrace trait with low iron and ferritin levels. The second, third and fourth group were compared with the first one. The conclusion is that the presence of HbOThrace leads to a mild hypochromic anemia, with no clinical findings, but the coexistence of beta zero gene or iron deficiency produces more pronounced laboratory findings and even clinically evident anemia.
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PMID:HbOThrace trait, HbOThrace hemoglobinopathy and HbOThrace/Hb beta zero hemoglobinopathy: a retrospective study of 118 cases. 1020 93

In this clinical investigation 35 patients under mechanical ventilation were studied. It was possible to establish the precision of two pulse oximeters of different brands. The performance of these equipments was evaluated by comparing data with the hemo-oximeter and a statistical analysis employed the student t test. Results showed that bias between oximeters reading and hemo-oximeter was similar for both instruments. Eventually critical patients may present conditions that limit the use of this technique. The study showed that the discrepancy in the results observed may be attributed to the presence of the methemoglobin and possible to anaemia associated to hypoxia.
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PMID:[Pulse oximetry for the evaluation of oxygen transport in patients in critical condition]. 1073 54


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