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

It has not yet been clarified whether prilocaine-induced methemoglobinemia is a problem in patients with chronic anemia. We therefore performed supraclavicular brachial blockade for upper limb surgery (6 mg/kg prilocaine 2% + 0.1 IU vasopressin/ml) in ten female patients with chronic renal failure (mean Hb 8.19%) requiring hemodialysis. Before the blockade, a catheter was inserted into the opposite internal jugular vein and blood samples were drawn before and 10, 15, 20, 30, 45, 60, 90, 120 and 180 min after injection. Plasma prilocaine concentrations and methemoglobin levels were within the ranges measured by other authors in healthy patients. There was no correlation between plasma prilocaine levels and methemoglobinemia. We therefore consider prilocaine to be a safe local anesthetic in patients with renal failure and chronic anemia.
 ...
PMID:[Supraclavicular plexus blockade using prilocaine in patients with chronic anemia]. 271 Sep 68

Clinical, hematologic and hemoglobin composition data on the first case of Hb 0-Arab in association with beta 0-thalassemia in Yugoslavia are reported here. The propositus was a 26-years-old female from Strumica who was admitted to the hospital for several times because of anemia, hepatosplenomegaly, occasional abdominal pains, malaise and fatigue. Laboratory results presented: Hb 10.0 g/dl, RBC 3.84.10(12)/L, PCV 0.260 l/l, MCV 68 fl, MCH 26 pg, reticulocyte count 1.8%, anisopoikilocytosis, polychromasis, numerous target cells, total bilirubin 2.1 mg/dl, (indirect 1.7 mg/dl), serum-Fe 32.3 microM/L. A starch gel electrophoresis of hemolysate provided evidence for the presence of abnormal hemoglobin (approximately 85%) and Hb F (approximately 15%); the Hb A was absent. Familial screening showed her father was heterozygous for the abnormal hemoglobin, whereas the mother was heterozygous for beta-thalassemia. In vitro biosynthesis disclosed a total absence of beta globin and reduced synthesis of beta x x and gamma globin. The alpha/beta x + gamma-globin ratio was 1.77 (normal, 1.0 + 0.1). Amino acid analysis revealed that lysine substituted for glutamic acid at the position one hundred twenty-one of the beta chain (= Hb 0-Arab or beta 121 Glu----Lys).
 ...
PMID:[Hemoglobin O Arab in interaction with beta 0-thalassemia]. 273 98

Dapsone, a sulfone compound used in the treatment of leprosy and, more recently, Pneumocystis carinii pneumonia, produces as a major side effect a hemolytic anemia. This anemia is characterized by oxidation of hemoglobin to methemoglobin and increased splenic uptake of red blood cells. Using a rat model, Grossman and Jollow (J. Pharmacol. Exp. Ther. 244: 118-125, 1988) found that dapsone hydroxylamine (DDS-NOH), a dapsone metabolite, is responsible for its hemolytic effect in vivo. DDS-NOH also promotes hemoglobin binding to SH groups on rat red cell membrane proteins (Budinsky et al., FASEB J. 2: A801, 1988). Since the binding of hemoglobin and other reagents (e.g., N-ethylmaleimide) to membrane SH groups has been associated with increased K transport in red blood cells, we examined the effect of DDS-NOH on K efflux from rat red blood cells in vitro. Cells shrink when exposed to DDS-NOH (100 microM) in media with plasma-like ionic composition. This shrinkage is prevented if extracellular K is raised to 110 mM or if intra- and extracellular Cl are replaced by methylsulfate (MeSO4), suggesting involvement of a K-Cl cotransport pathway. Indeed, 100 microM DDS-NOH produces a 4- to 5-fold increase in K efflux in cells containing Cl but less than a 2-fold increase in cells containing MeSO4. This stimulatory effect is specific for K; Na efflux is slightly inhibited by 100 microM DDS-NOH. The concentrations of DDS-NOH required for half-maximal stimulation of Cl-dependent K efflux (53 microM) is similar to its half-maximal hemolytic concentration in rats (approximately 100 microM). Furthermore, the stimulation of Cl-dependent K efflux by DDS-NOH is greater than 80% reversed by subsequent treatment of the cells with dithiothreitol, suggesting involvement of SH groups. Our results indicate that DDS-NOH exposure stimulates an apparent K-Cl cotransport in rat red blood cells, resulting in cell shrinkage under physiological ionic conditions. Since shrinkage of red blood cells renders them less deformable (Mohandas et al., J. Clin. Invest. 66: 563-573, 1980), this suggests a pathophysiological mechanism whereby DDS-NOH exposure in vivo could promote increased splenic uptake of red blood cells and hemolytic anemia.
 ...
PMID:Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone. 291 57

Hemoglobin as a vehicle for oxygen carries roughly 65 times the volume of oxygen that would otherwise be transported by simple solution in plasma. Conformational shifts of the molecule induce a cooperative oxygen-hemoglobin affinity. This property is reflected in the sigmoidal shape of the oxygen-hemoglobin dissociation curve. The affinity of hemoglobin is affected by temperature, hydrogen ions, carbon dioxide, and intraerythrocytic 2,3-DPG, with all these factors mutually influencing each other. Physiologic conditions associated with shifts in hemoglobin-oxygen affinity are oxygen uptake in the lung, oxygen delivery in the capillaries, and particularly oxygen delivery in working muscle, diaplacental oxygen transfer, and the regulation of erythropoesis. Hemoglobin-oxygen affinity attains pathological significance for oxygen supply during respiratory or metabolic alkalosis when the hemodynamic and tissue responses of the individual are limited: the increased affinity can critically lower capillary oxygen tension. Methemoglobin and carbon monoxide shift the oxygen dissociation curve to the left, so that intoxication with both substances reduces both total oxygen capacity and oxygen delivery of the remaining hemoglobin able to bind oxygen. This effect of methemoglobin and carbon monoxide must be considered in intensive care of intoxicated victims. Transfusions of large volumes of stored red cells, whose hemoglobin shows high affinity, can force the capillary oxygen tension down, especially in patients with impaired cardiac performance. The lowered oxygen affinity of patients with chronic renal disease and anemia must be preserved by avoiding an increase in the acidotic plasma pH. In the neonate, hemoglobin possesses a high affinity for oxygen physiologically; the hemodynamic reserve of the neonate is limited. Therefore, the hemoglobin content plays a crucial role in oxygen transport capacity during the initial months of extrauterine life. Consequently, red cell transfusion must be started much earlier in neonatal surgery than in adults. The red cells must be fresh, or at best "rejuvenated". Normally, oxygen affinity is not relevant for oxygen supply, but the position of the oxygen-hemoglobin dissociation curve may be a critical factor in the situations described above, particularly when blood flow is additionally restricted.
 ...
PMID:[Affinity of oxygen for hemoglobin--its significance under physiological and pathological conditions]. 331 47

Hb Mississippi was discovered in a 6-year-old Chinese girl with chronic anemia and thalassemia intermedia. Family studies revealed that she had inherited the Hb Mississippi from her father as well as inheriting a gene for beta+-thalassemia from her mother. Electrophoretic analyses of the hemolysate of the father of the father and the proband on polyacrylamide gels at pH 8.6 showed that the abnormal hemoglobin had three distinct mobilities. A similar pattern was also observed by isoelectricfocusing. In addition, multiple abnormal peaks were observed by high performance liquid chromatographic hemoglobin separations as well as high performance liquid chromatographic globin chain separation. Structural analysis of the abnormal hemoglobin demonstrated a single abnormality; the substitution of serine to cysteine at position 44 (CD3) of the beta-globin chain. Since CD3 is on the surface of the beta-globin chain, it was thought that polymerization of the abnormal hemoglobin by disulfide linkages might have been responsible for the anomalous behavior on electrophoresis and high performance liquid chromatography. Gel filtration chromatography on G-200 Sephadex confirmed this supposition and demonstrated that the abnormal globin chain polymerized with itself as well as with other globin chains.
 ...
PMID:Hb Mississippi [beta 44(CD3)Ser----Arg]: a new variant with anomalous properties. 342 43

Hemoglobin Chico was discovered in an asymptomatic 3-year-old boy when a mild anemia was detected by a routine blood count. Affected individuals in three generations are also mildly anemic. The abnormal hemoglobin amounts to about 45% of the total. It separates from Hb A by cellulose acetate electrophoresis at pH 8.5 with a mobility similar to Hb J but does not separate in citrate agar at pH 6.2. Stability in isopropanol is slightly decreased. Its structure differs from the normal by the substitution of a threonyl residue for lysyl residue at position 66(E10) of the beta chain. The P50 of the oxygen equilibrium curve of whole blood at 37 degrees C was 38 torr compared with controls of 27 +/- 2 torr. The P50 binding studies of the isolated Hb Chico revealed a unique right shift of the equilibrium curve with an oxygen binding constant (1/P50) about half of normal. The remaining allosteric properties were essentially normal. This significant decrease in oxygen affinity appears to be due to changes in the heme region which result from the substitution of the normal beta 66 lysyl by the threonyl residue.
 ...
PMID:Hemoglobin Chico [beta 66(E10)Lys----Thr]: a new variant with decreased oxygen affinity. 342 44

The acute toxicity of hydroxylamine sulfate (HS) and phenylhydrazine hydrochloride (PHZ) were compared in the rabbit and rat following a single 24-hr dermal exposure. The test materials were applied topically and occluded under a plastic or gauze cover or were injected sc. Distilled water served as a control. HS and PHZ produced similar hematotoxic effects consisting of methemoglobin formation, anemia, and reticulocytosis. HS and PHZ proved to be more toxic to the rabbit than to the rat although both chemicals produced similar hematological effects at equivalent dose levels within the same species. HS proved strikingly more toxic when administered under plastic than under gauze despite the fact that both methods included occlusion. PHZ toxicity was less variable with exposure method. HS and PHZ were lethal to the rabbit but no deaths occurred in the rat. The results of this study indicate that HS and PHZ show similar hematotoxicity and, therefore, the clinical data available on PHZ may be useful in predicting the hematological effects of HS on humans.
 ...
PMID:Toxicity of hydroxylamine sulfate following dermal exposure: variability with exposure method and species. 360 44

For evaluation of subchronic toxicity of the two single-ring nitroaromatics, p-nitroaniline (PNA) and p-nitrochlorobenzene (PNCB), groups of 10 male and 10 female Sprague-Dawley rats were exposed to an aerosol/vapor of PNA in isopropanol at target concentrations of 0, 10, 30, or 90 mg/m3 or to PNCB vaporized from a solution in ethylene glycol monoethyl ether at target concentrations of 0, 5, 15, or 45 mg/m3 for 6 hr/day, 5 days/week for 4 weeks. Clinical signs of toxicity, body weights, results of ophthalmoscopic exam, hematology and clinical chemistry tests, organ weights, gross and histopathological changes were recorded. Exposure to PNA or PNCB resulted in a dose-related increase in blood methemoglobin levels. Mean red blood cell counts, hematocrit, and hemoglobin were significantly decreased in mid and high level animals exposed to PNCB. Mean spleen weights (absolute and relative to body weight) were significantly increased at the high dose levels in the two studies. A slight increase in spleen weights was also observed at the low concentration level in the PNA study. Absolute and relative liver weights also were increased among animals exposed to 45 mg/m3 PNCB. Microscopic changes were observed mainly in the spleen and included an increase in intensity of extramedullary hematopoiesis and hemosiderosis with both compounds. Spleens of animals exposed to PNCB also exhibited congestion. Neither PNA nor PNCB exhibited significant toxicological effects other than those of methemoglobinemia, anemia, and splenic changes classically associated with nitroaromatics at levels significantly above presently accepted occupational standard. Our data suggest that the current TLV for PNA which is 3 mg/m3 will provide adequate protection to the workers. OSHA's PEL of 1 mg/m3 for PNCB is to be preferred over the current TLV of 3 mg/m3 to provide a comparable margin of safety.
 ...
PMID:Subchronic inhalation toxicity of p-nitroaniline and p-nitrochlorobenzene in rats. 371 33

Deficiency in human G-6PD is a widespread X-linked disorder, which is mainly characterized by susceptibility to hemolytic anaemia after the ingestion of certain drugs or toxic substances (e.g. pyrimidine derivates contained in fava beans). G-6PD deficiency in hemizygous males in easily detectable since enzymatic activity is almost absent. In heterozygous subjects the determination of enzymatic activity on red cell lysate cannot detect a partial G-6PD deficiency. Cytochemical methods as methemoglobin reduction test or tetrazolium reduction test are more sensitive than spectrophotometric quantitative test, but are not suitable for screening purposes. We measured both G-6PD activity and 6-PGD activity in G-6PD heterozygous females and we evaluated the G-6PD/6PGD ratio. We tested this ratio also in thalassemic traits and in G-6PD heterozygotes with thalassemic trait in order to detect the interference of thalassemic pathology with the phenotypic expression of the gene for G-6PD. We found that the mean G-6PD values were statistically reduced in G-6PD heterozygous females; on the contrary the measurement of true G-6PD activity alone is not a good tool for discriminating heterozygous subjects with and without thalassemic trait. Actually 100% and 79% of values observed were in the normal range +/- 2 DS respectively. The mean G-6PD/6-PGD ratio in heterozygotes for G-6PD deficiency with and without thalassemic trait was lower than normal and the individual values of G-6PD/6-PGD ratio were in the normal range +/- 2 DS only in a few subjects (8.3% and 10.7% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase ratio in the identification of glucose-6-phosphate dehydrogenase heterozygosity]. 372 8

Cats given DL-methionine (1 g/kg of body weight/day) developed severe hemolytic anemia with marked increase of methemoglobin (MetHb) concentration and Heinz-body formation at treatment-day 6 to 10. Cats fed 0.5 g of methionine/kg for 52 days had a moderate Heinz-body hemolytic anemia with methemoglobinemia at treatment days 17 to 31, but thereafter recovered from the anemia despite continuation of methionine feeding, indicating an adaptation of the cats. In vitro, significant (P less than 0.01) increases of MetHb concentration and Heinz-body formation were observed when RBC were incubated with plasma from cats fed (1 g of methionine/kg) or with 10 mM 3-methylthiopropionate, a product of methionine catabolism. However, these increases were not observed when RBC were incubated with 10 mM methionine. Seemingly, excessive methionine intake leads to production of an intermediate of the methionine catabolism that may affect RBC directly as an intensive oxidizing agent, resulting in an excessive oxidation of hemoglobin to MetHb and Heinz-body formation.
 ...
PMID:Methionine toxicosis in cats. 382 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>