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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroma-free haemolysates of red cells from patients with acute or latent anaemia inhibit the NADH oxidase activity of submitochondrial particles from beef heart. The inhibitory activities appeared significantly more frequently in anaemic patients than in normal persons and are likely due to the action of a factor which is identical or similar to the inhibitory protein RF present in rabbit reticulocytes. The possible use of the inhibitor assay for clinical purpose is under discussion.
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PMID:Activity of the respiratory inhibitor RF in human red cells in anaemia. 59 52

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.
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PMID:[Effects of ethylene glycol on drug metabolizing enzymes in rat liver]. 202 9

The changes in the cytochrome P-450 enzyme system of rat liver, lung and brain after inhalation of ethylene oxide were studied. When Wistar male rats were exposed to 500 ppm ethylene oxide three times a week for three months, they showed a suppressed gain of body weight. Therefore, the present study was done using pair-fed rats. Haematological examination revealed normocytic and normochromic anemia. Liver and renal functions were normal. The cytochrome P-450 enzyme system in the lung and brain were not affected. However, hepatic cytochrome P-450 and protoheme decreased by 28% and 19%, respectively. Hepatic total microsomal protein, cytochrome b5, NADPH-cytochrome c reductase and NADH-ferricyanide reductase were not affected. The activity of hepatic heme oxygenase showed a 2-fold increase. These results suggest that the heme moiety of hepatic cytochrome P-450 was primarily attacked by exposure of ethylene oxide and the cellular heme balance in liver was altered.
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PMID:[Effects of chronic exposure of ethylene oxide, especially on heme metabolism]. 336 71

1. Chronic marginal riboflavin deficiency was induced in groups of weanling rats by feeding a deficient diet supplemented with 0, 0.5, 1.0 and 1.5 mg riboflavin/kg diet. Ad lib.- and pair-fed controls received 3.0 and 15 mg riboflavin/kg diet respectively. 2. Serial measurement of erythrocyte NAD(P)H2 glutathione oxidoreductase (glutathione reductase; EC 1.6.4.2) and its activation coefficient revealed that after 12 weeks a steady-state of deficiency had been reached following initial fluctuations in status; the animals were then killed, and their tissues analysed. 3. Food intake, growth rate and the appearance of pathological signs were directly proportional to riboflavin content; however relative liver weight was increased above control levels only in the most-severely-deficient group, and anaemia was not detected in any group. 4. The activation coefficient of glutathione reductase in erythrocytes and liver was closely related to dietary riboflavin content; that of skin responded maximally even in the least-severely-depleted animals. 5. Hepatic and renal flavin contents were directly proportional to dietary riboflavin, FAD being conserved at the expense of riboflavin and FMN. ATP:riboflavin 5-phosphotransferase (flavokinase; EC 2.7.1.26) activity was reduced, even in the least-severely-deficient animals; ATP:FMN adenylyltransferase(FAD pyrophosphorylase; EC 2.7.7.2) was increased in liver, but only in the most-severely-deficient animals. 6. Hepatic succinate:(acceptor) oxidoreductase (succinate dehydrogenase; EC 1.3.99.1) activity fell sharply between 1.5 and 0.5 mg riboflavin/kg diet, producing an S-shaped dose-response curve; it showed smaller or less specific changes in other tissues such as brain, skin and intestine. NADH:(acceptor) oxidoreductase (NADH dehydrogenase; EC 1.6.99.3) activity declined in liver and intestine, but not in skin or brain. 7. The activation coefficient of glutathione reductase was correlated strongly with nearly all the riboflavin-sensitive variables measured, once equilibrium had been reached in this chronic deficiency model, and it was particularly strongly correlated with hepatic and renal FAD levels. Under equilibrium conditions, therefore, it appears to represent a good index of the extent of riboflavin deficiency, and significant changes in flavin levels and enzymes in the internal organs were detected even under conditions of marginal deficiency, associated with relatively small increases in the activation coefficient.
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PMID:A biochemical evaluation of the erythrocyte glutathione reductase (EC 1.6.4.2) test for riboflavin status. 2. Dose-response relationships in chronic marginal deficiency. 747 Apr 38

Diminished availability of oxygen at the cellular level might account for organ dysfunction in sepsis. Although the classical forms of tissue hypoxia due to hypoxemia, anemia, or inadequate perfusion all might be important under some conditions, it seems increasingly likely that a fourth mechanism, namely cytopathic hypoxia, might play a role as well. The term cytopathic hypoxia is used to denote diminished production of adenosine triphosphate (ATP) despite normal (or even supranormal) PO2 values in the vicinity of mitochondria within cells. At least in theory, cytopathic hypoxia could be a consequence of several different (but mutually compatible) pathogenic mechanisms, including diminished delivery of a key substrate (e.g., pyruvate) into the mitochondrial tricarboxylic acid (TCA) cycle, inhibition of key mitochondrial enzymes involved in either the TCA cycle or the electron transport chain, activation of the enzyme, poly-(ADP)-ribosylpolymerase (PARP), or collapse of the protonic gradient across the inner mitochondrial membrane leading to uncoupling of oxidation (of NADH and FADH) from phosphorylation of ADP to form ATP. Tantalizing, but limited, data support the view that cytopathic hypoxia occurs in both animals and patients with sepsis or endotoxemia.
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PMID:Cytopathic hypoxia in sepsis. 924 46

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymic defense consists of scavenging molecules that are endogenously produced (GSH, ubiquinols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiquinols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.
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PMID:Interaction of antioxidants and their implication in genetic anemia. 1060 86

The erythrocyte is a highly specialized cell whose main functions are oxygen transport and the mediation of carbon dioxide transport. Energy production in the mature erythrocyte depends on glycolysis, with glucose as the principal substrate. Glycolysis and the oxidative pentose phosphate pathway generate NADH and NADPH to reduce methemoglobin, which is being continuously produced, and the antioxidant glutathione, which is present in high concentrations. Red blood cells are equipped with a highly effective antioxidant defense even without the glutathione system. Compared with other cell types, they possess high activities of the most important antioxidant enzymes. Most of the nonenzymatic antioxidant capacity of whole blood is likewise localized in the erythrocytes. Circulating red cells are mobile free radical scavengers and provide antioxidant protection to other tissues and organs. An imbalance between pro-oxidant reactions and antioxidant defense is described in patients with chronic renal failure. Oxidative stress increases as antioxidant defenses are weakened by pro-oxidant hemodialysis factors; it increases further still in renal anemia with a very low red cell count. Thus in terms of free radical metabolism, the only arguments remaining over the complete correction of renal anemia are those in favor, with none against.
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PMID:Erythrocyte free radical and energy metabolism. 1074

A functional requirement for all hemoglobin-based oxygen carriers (HBOCs) is the maintenance of the heme-iron in the reduced state. This is necessary for the reversible binding/release of molecular oxygen and minimization of methemoglobin (Fe+3) formation. Acellular hemoglobins are especially susceptible to oxidation and denaturation. In the absence of the intrinsic reducing systems of the red blood cell, the reduced heme-Fe+2 can be oxidized to form increasing levels of methemoglobin that can give rise to free radicals and oxidative cellular damage. If acellular HBOCs are to be utilized as red cell substitutes for oxygen delivery, these carriers must be stabilized in the plasma, the carrier medium. Normal plasma contains reducing components, such as ascorbic acid and glutathione, that can afford protection to these acellular HBOCs through electron-transfer mediated processes. For these components to provide effective reduction to an HBOC, a favorable reduction potential difference must exist between the reducing agent and the HBOC. Using a modified thin-layer spectroelectrochemical method, a determination of the formal reduction potential (vs. Ag/AgCl) of several oxygen carriers, including monomeric myoglobin, tetrameric HbA and HbS, chemically cross-linked HbXL99alpha, polymerized oxyglobin (FDA approved for canine anemia), and the natural cross-linked polymeric Lumbricus hemoglobin, have been determined. In contrast to the negative formal reduction potentials (-155 to -50 mV) obtained for Mb, HbA, HbS, HbXL99alpha, and oxyglobin, Lumbricus hemoglobin exhibited a positive formal reduction potential (approximately 100 mV). These results may help explain the greater effectiveness of the tested reducing agents to reduce met Lumbricus hemoglobin, compared to the other HBOCs, back to the required reduced form necessary for physiological binding/release of oxygen. Each reducing agent was capable of reducing met Lumbricus hemoglobin to the fully reduced state, although the kinetics of these reactions were different. HbA, HbXL99alpha, and oxyglobin were only partially reduced (10 to 37%) by glutathione, beta-NADH, and ascorbic acid under similar conditions.
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PMID:Role of redox potential of hemoglobin-based oxygen carriers on methemoglobin reduction by plasma components. 1200 Feb 25

Mycoplasma suis, the causative agent of porcine infectious anemia, has never been cultured in vitro and mechanisms by which it causes disease are poorly understood. Thus, the objective herein was to use whole genome sequencing and analysis of M. suis to define pathogenicity mechanisms and biochemical pathways. M. suis was harvested from the blood of an experimentally infected pig. Following DNA extraction and construction of a paired end library, whole-genome sequencing was performed using GS-FLX (454) and Titanium chemistry. Reads on paired-end constructs were assembled using GS De Novo Assembler and gaps closed by primer walking; assembly was validated by PFGE. Glimmer and Manatee Annotation Engine were used to predict and annotate protein-coding sequences (CDS). The M. suis genome consists of a single, 742,431 bp chromosome with low G+C content of 31.1%. A total of 844 CDS, 3 single copies, unlinked rRNA genes and 32 tRNAs were identified. Gene homologies and GC skew graph show that M. suis has a typical Mollicutes oriC. The predicted metabolic pathway is concise, showing evidence of adaptation to blood environment. M. suis is a glycolytic species, obtaining energy through sugars fermentation and ATP-synthase. The pentose-phosphate pathway, metabolism of cofactors and vitamins, pyruvate dehydrogenase and NAD(+) kinase are missing. Thus, ribose, NADH, NADPH and coenzyme A are possibly essential for its growth. M. suis can generate purines from hypoxanthine, which is secreted by RBCs, and cytidine nucleotides from uracil. Toxins orthologs were not identified. We suggest that M. suis may cause disease by scavenging and competing for host' nutrients, leading to decreased life-span of RBCs. In summary, genome analysis shows that M. suis is dependent on host cell metabolism and this characteristic is likely to be linked to its pathogenicity. The prediction of essential nutrients will aid the development of in vitro cultivation systems.
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PMID:Complete genome sequence of Mycoplasma suis and insights into its biology and adaption to an erythrocyte niche. 2157 7

Energetic metabolism plays an essential role in the differentiation of haematopoietic stem cells (HSC). In Fanconi Anaemia (FA), DNA damage is accumulated during HSC differentiation, an event that is likely associated with bone marrow failure (BMF). One of the sources of the DNA damage is altered mitochondrial metabolism and an associated increment of oxidative stress. Recently, altered mitochondrial morphology and a deficit in the energetic activity in FA cells have been reported. Considering that mitochondria are the principal site of aerobic ATP production, we investigated FA metabolism in order to understand what pathways are able to compensate for this energy deficiency. In this work, we report that the impairment in mitochondrial oxidative phosphorylation (OXPHOS) in FA cells is countered by an increase in glycolytic flux. By contrast, glutaminolysis appears lower with respect to controls. Therefore, it is possible to conclude that in FA cells glycolysis represents the main pathway for producing energy, balancing the NADH/NAD+ ratio by the conversion of pyruvate to lactate. Finally, we show that a forced switch from glycolytic to OXPHOS metabolism increases FA cell oxidative stress. This could be the cause of the impoverishment in bone marrow HSC during exit from the homeostatic quiescent state. This is the first work that systematically explores FA energy metabolism, highlighting its flaws, and discusses the possible relationships between these defects and BMF.
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PMID:Defects in mitochondrial energetic function compels Fanconi Anaemia cells to glycolytic metabolism. 2831 53


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