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)

Severe copper deficiency was induced in rats by rearing nursing dams and their offsprings on a semisynthetic diet comprising all the requisite nutrients and trace metals except copper. The copper-deprived rats exhibited growth retardation, severe anaemia, loss of caeruloplasmin, decrease of cytochrome oxidase, accumulation of salt-soluble collagen and a drastic decrease in iron in plasma and liver. Apart from these characteristic signs of deficiency, a marked inhibition of protein synthesis was found to occur both in vivo and in cell-free liver preparations. The curtailed ability to carry out endogenously coded amino acid incorporation into protein contrasted with the unimpaired poly(U)-acid-directed phenylalanine polymerization. This inhibition pattern, as well as the attendant disaggregation of the liver polyribosomes, suggested that the primary biosynthetic lesion was located at the stage of peptide-chain initiation. Concurrently with this alteration there was a pronounced depletion of the hepatic ATP content, associated with a parallel depression of mitochondrial respiration and an enhancement of ATPase activity. Supplementation of the copper-deficient diet with a 2-4-fold excess of iron (relative to the standard diet) prevented growth retardation and anaemia and restored normal energy metabolism, as well as unimpaired protein-synthesizing capacity. The conclusion that these disturbances were primarily determined by the secondary iron deficiency was also borne out by the finding that similar alterations occurred in rats maintained on a copper-sufficient but iron-deficient diet. On the other hand, the iron-fortified diet failed to reverse the other signs of copper deficiency, namely the loss of caeruloplasmin, the diminished rate of cytochrome oxidase and the increase of soluble collagen. The interrelations between the various biochemical lesions induced by deprivation of copper or iron are discussed and the possible role of ATP depletion in determining the derangement of protein synthesis is considered.
 ...
PMID:Biochemical lesions in copper-deficient rats caused by secondary iron deficiency. Derangement of protein synthesis and impairment of energy metabolism. 625 58

The survival of erythrocytes (RBC) is shortened in uremia, and it has been shown that calcium influx into RBC evoked crenation and increased their rigidity. The high blood levels of parathyroid hormone (PTH) may augment entry of calcium into RBC and hence affect their integrity. We examined the effect of PTH on osmotic fragility of human RBC and investigated the mechanisms through which PTH interacts with RBC. Both the amino-terminal (1-34) PTH and the intact (1-84) PTH, but not the carboxy-terminal (53-84) PTH, produced significant increases in osmotic fragility. This effect was abolished by prior inactivation of the hormone. There was a dose-response relationship between both moieties of PTH and the increase in osmotic fragility. This action of PTH required calcium, was mimicked by calcium ionophore, and was partially blocked by verapamil. PTH caused significant influx of (45)Ca into RBC, which was not associated with potassium leak. The hormone did not affect water content of RBC. Scanning electron microscopy revealed that the incubation of RBC with PTH was associated with the appearance of membrane filamentous extensions, which anchor RBC together. Inhibition of glycolytic activity of RBC with NaF or inhibition of Na-K-activated ATPase with ouabain did not abolish the effect of PTH on osmotic fragility. PTH did not stimulate RBC Na-K-activated ATPase or Mg-dependent ATPase but caused marked and significant stimulation of Ca-activated ATPase. The basal activity of the RBC adenylate cyclase was low and PTH produced only a modest stimulation of this enzyme. Both cyclic AMP and dibutyryl cyclic AMP had no effect on osmotic fragility. THE DATA INDICATE THAT: (a) the RBC is a target organ for PTH, (b) the hormone increases osmotic fragility of RBC, and (c) this effect of PTH is due to enhanced calcium entry into RBC. We suggest that the increased calcium influx may affect the spectrin-actin of the cytoskeletal network of the RBC and may alter the stability and integrity of the cell membrane. This action of PTH on the RBC could be, at least in part, responsible for the shortened survival of RBC in uremia, and assign a new role for PTH in the pathogenesis of the anemia of uremia.
 ...
PMID:Effect of parathyroid hormone on osmotic fragility of human erythrocytes. 628 9

A rare familial case of hereditary stomatocytosis with hemolytic anemia, increased autohemolysis, increased osmotic fragility, and shortened erythrocyte survival is described. The erythrocytes were abnormally permeable to sodium and potassium. In addition, "Na-K pump" rate of the red blood cells was increased, while Na+-K+-ATPase, Mg2+-ATPase and Mg2+-Ca2+-ATPase activities were within normal limits. Splenectomy induced marked improvement of anemia.
 ...
PMID:A family of hereditary stomatocytosis associated with normal level of Na+-K+-ATPase activity of red blood cells. 630 Dec 65

In acutely uremic animals, the contractile force of the heart is consistently increased; such an increase can be dissociated from changes of afterload or catecholaminergic drive. It is associated with diminished sarcolemmal Na,K-ATPase activity in the heart which, in turn, may be related to increased levels of endogenous digitalis-like substances (endigens) that have been postulated to represent a natriuretic factor. In patients with chronic uremia, myocardial contractility is usually normal, but occasionally there may be heart failure unrelated to pre-existing hypertension, coronary heart disease, anemia, fluid overload, or other recognizable factors. So far, the experimental basis for this clinical observation is uncertain. Possible causes for the clinical syndrome include an excess of parathyroid hormone or cardiodepressor substances. There is experimental evidence of impaired cardiac response to beta adrenergic agonists, e.g., decreased isoproterenol-dependent calcium uptake, diminished inotropic and chronotropic responses. In acutely uremic rats, cardiac cyclic AMP levels are high but can be reversed by beta blockers. Heart calcium content is variable and heart weight is constantly increased in acutely uremic rats, despite decreased skeletal muscle mass. The change in heart weight is not related to anemia, to an excess of parathyroid hormone, or to sympathetic activity; its cause remains unknown. Experimental studies to date have shown a variety of abnormalities, but do not provide a uniform concept of the mechanisms or an explanation for the cardiac dysfunction so often observed in patients with uremia.
 ...
PMID:Cardiac function in experimental uremia. 636 51

The high incidence of cardiac complications in endstage renal failure is not only related to the chronic pressure load of the left ventricle, although the proportion of patients with elevated blood pressure increases from 53 to 81% as reno-parenchymal disease progresses. Other factors as anemia, hyperparathyroidism, autonomic neuropathy and retention of electrolytes, metabolic products of toxins may cause damage to the heart. It is a matter of discussion whether uremia itself causes cardiomyopathy. Findings of a reduced Ca++-uptake during beta-adrenergic stimulation and a reduced reaction of (Na+, K+)-ATPase to digitalis suggest a basic change of myocardial membrane metabolism. Retention of an "endogenous digitalis" could help to explain some contradictory results.
 ...
PMID:[Reno-cardiac interactions in kidney failure (author's transl)]. 700 26

The examination of septic children has revealed characteristics of iron and red cell metabolism: deep and persistent hypotransferrinemia, normo- or hypersideremia, normal ferritin levels. Red cells of septic children contain low concentrations of ATPase, histidine, lipoproteins, there is compensatory enhancement of 2,3-DPG, G-6-PD SH-group activity. In terminal sepsis the activity of the above parameters drastically falls entailing hemolysis, anemia and severe hypoxia.
 ...
PMID:[The metabolic activity of the erythrocytes and the characteristics of ferrokinetics in children with sepsis]. 802 Jul 13

In this study rhEPO, 70 U/kg, was subcutaneously administered two times a week for eight weeks to twelve nondialysed patients with renal anaemia and chronic renal failure. Renal function tests, blood pressure, Hb, Hct, FENa and Na-K-ATPase enzyme activity before and after administration of rhEPO have been studied. We have searched for correlations, if any, between these parameters. After the treatment period mean Hb concentration and mean Hct values increased from 7.5 +/- 0.3 to 8.6 +/- 0.5 g/dl and from 22.5 +/- 1.2 to 26.7 +/- 1.6%, respectively (p < 0.05), whereas no significant differences between pretreatment and posttreatment Cr and CrCl values were found (p > 0.05). No changes in blood pressure were found throughout the study. While mean FENa decreased from 10.2 +/- 1.6 to 6.15 +/- 1.05% (p < 0.05), mean Na-K-ATPase enzyme activities decreased from 0.120 +/- 0.016 to 0.095 +/- 0.025 mumol Pi/h/mg protein (p > 0.05) after treatment. In conclusion, subcutaneous administration of rhEPO, at doses of 70 U/kg twice a week in nondialysed patients increased Hb and Hct values. A significant decrease of FENa was observed after rhEPO treatment and there was no correlation between Na-K-ATPase enzyme activity and FENa.
 ...
PMID:Effects of recombinant human erythropoietin on sodium balance in nondialysed children with chronic renal failure. 817 82

The activity of Na+, K(+)-ATPase (ouabain-inhibited 86Rb influx), Na+, K+ cotransport (ouabain-insensitive furosemide-inhibited 86Rb or 22Na influx), Na+/Na+ exchange (ouabain-insensitive phloretin-inhibited 22Na influx) and Na+/Li+ exchange (ouabain-insensitive Na0(+)-depended Li+ efflux) as well as the passive permeability of the erythrocyte membrane for Na+, K+ and Li+ have been studied in patients with primary (microspherocytosis, hemoglobinopathy) and secondary (autoimmune) hemolytic anemia. The activities of the Na+, K(+)-pump and Na+, K(+)-cotransport were increased in patients with microspherocytosis-by 45% and 70%, respectively. In patients with hemoglobinopathy the Na+/Li+ exchange and passive permeability for K+ were increased 2-3-fold in comparison with the control with the control group. The increased passive permeability for K+ may partly be due to the increased K+, Cl(-)-cotransport. In patients with autoimmune anemia the 3-fold increase in the passive permeability for monovalent cations and the 2-fold increased activity of Na+, K+ cotransport were found. There was no significant correlation between the Na+/Na+ and Na+/Li+ exchange which suggests that the cellular mechanisms of activity control in those ion transport systems differ essentially. No correlation was found between the passive permeability for Na+ and K+ either. These data indicate that simple diffusion (leakage) is not the only pathway for the passive permeability of the erythrocyte membrane for monovalent cations.
 ...
PMID:[Transport of ions into human erythrocytes in various forms of hemolytic anemia: a correlation analysis]. 836 10

This paper gives an overview of the hypotheses concerning the mechanisms of inorganic lead toxicity on cells and tissues, with emphasis on the effect of low-concentration lead. Inhibition of heme synthesis is responsible not only for lead-induced anaemia, but also for accumulation of delta-aminolaevulinic acid (ALA) and for lowering the concentration of cytochromes contained in the mitochondrial respiratory chain. Auto-oxidation of ALA is thought to result in the formation of free radicals. On the other hand, lead replaces ionic calcium in its role as second cell messenger. This mechanism would explain the abnormalities observed in synaptic transmission, arteriolar vasoreactivity and functioning of such cells as osteoclasts and osteoblasts. Nuclear toxicity, with abnormal expression of DNA genes and inhibition of certain enzymes such as membrane Na+/K+ ATPase, are also considered. The mechanisms of tissue toxicity are discussed.
 ...
PMID:[Physiopathology of inorganic lead poisoning]. 837 37

The frequency of cardiovascular diseases in patients with end-stage renal disease (ESRD) is high, since hypotension, hyperlipidemia, advanced age, diabetes and other systemic diseases that may affect the heart are common in such patients. In addition to the pre-existing factors for cardiovascular disease, there are also predisposing factors that relate specifically to life on hemodialysis (HD). These include myocardial stress related to recurrent volume expansion and contraction, anemia, secondary hyperparathyroidism, excess or deficit of certain trace metals that may act as enzyme cofactors, and factors that inhibit myocardial ATPase. The prevalence, pathogenesis, and significance of these factors in ESRD patients are examined, and the potential roles of management are reviewed.
 ...
PMID:Cardiovascular complications in end-stage renal disease and hemodialysis patients. 904 18


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