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)

Male weanling rats were made copper deficient with a purified diet containing all known essential dietary nutrients except copper. Copper deficiency was verified by indirect (anemia, growth retardation, hypercholesterolemia, gross pathology, and abnormal electrocardiograms) and direct (tissue copper analysis) criteria. His bundle electrographic and electrocardiographic changes detected in the copper-deficient group consisted most notably of depressed His-Purkinje system conductivity and S-T segment depression. Phosphorus-31 nuclear magnetic resonance spectroscopic analysis of cardiac, renal, and hepatic tissue perchloric acid extracts revealed significant metabolic changes associated with the dietary copper deficiency, including a generalized marked decrease in ATP and phosphocreatine levels and a corresponding increase in inorganic orthophosphate and ADP levels in the various tissues. Tissue-specific changes consisting of elevated ribose 5-phosphate (heart), phosphocholine (heart), and inosine monophosphate (kidney) and decreased glycerol 3-phosphorylethanolamine (liver) and glycerol 3-phosphorylcholine (liver) levels were detected in copper-deficient rats. Microscopic examination of heart tissue from copper-deficient rats revealed extensive disruption of mitochondrial fine structure, including fragmentation of cristae and inner and outer mitochondrial membranes, which resulted in pronounced vacuolization throughout the tissue. Although the physiological and metabolic disturbances manifested in hearts from copper-deficient animals generally mimic myocardial responses to chronic ischemia, the observed changes are interpreted in a broader context to represent the appearance of a copper-dependent cardiomyopathy.
 ...
PMID:Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. 663 5

Erythropoietin corrects anemia and improves hemostasis, but on the other hand bears a risk of thrombotic complications. Therefore in the present study an attempt has been made to evaluate bleeding time, platelet functions and some hemostatic and fibrinolytic parameters in relation to blood and platelet serotonin before and after 1, 2, 4, 8 and 12 weeks of treatment. 22 chronically hemodialyzed patients were administered with human recombinant erythropoietin (rHuEPO) in a dose of 2000 IU s.c. 3 times a week. Bleeding time was shortened significantly as early as after 1 week of the therapy, whereas hematocrit and hemoglobin increased after 2 weeks. These changes lasted throughout the study. Only a transient rise in platelet count, collagen-induced platelet aggregation, beta-thromboglobulin and VIII:C activity were observed during therapy relative to baseline values. ADP- and arachidonic acid-induced platelet aggregation seemed to be unaffected by rHuEPO treatment, whereas a gradual and progressive enhancement in platelet aggregation in response to ristocetin was found, starting from the 2nd week of the therapy. It lasted throughout the study and correlated inversely with the bleeding time and positively with a rise in both blood and platelet serotonin. rHuEPO did not alter plasminogen, fibrinogen, platelet factor 4, alpha 2 macroglobulin levels, protein C activity and euglobulin clot lysis time. A decline in protein C and S concentrations and antithrombin III activity observed during the therapy were counterbalanced by a fall in the activity of alpha 2 antiplasmin, C1 esterase inhibitor and plasminogen activator inhibitor. It is concluded that rHuEPO may improve platelet/vessel wall interactions possibly by means of serotonergic mechanisms. A lowered activity of inhibitors of fibrinolysis may be regarded as a protection against a general tendency to thrombosis during rHuEPO therapy.
 ...
PMID:A study of platelet functions, some hemostatic and fibrinolytic parameters in relation to serotonin in hemodialyzed patients under erythropoietin therapy. 774 May 5

The mechanism of the inhibitory effects of chelators (desferrioxamine, EDTA, rutin, phenanthroline and ADP) on the production of oxygen radicals in the Fenton reaction and on lipid peroxidation of rat brain homogenates has been studied. It was found that the inhibitory effects of the chelators correlated well with their abilities to oxidize ferrous ions in solution and brain homogenates. On these grounds, it was concluded that the oxidation of Fe2+ ions inside a ferrous ion-chelator complex is a major mechanism of inhibitory effects of these chelators on free radical processes. It is proposed that this mechanism is also realized during therapeutic treatment with chelators of patients with "free radical" pathologies such as Fanconi anemia, beta-thalassemia and Diamond-Blackfan anemia.
 ...
PMID:Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat brain homogenates. 813 55

Chronic exposure of adult rats to dietary intake of cadmium (15 mg CdCl2/day/kg for 30 days) leads to development of anemia and thrombocytosis. Anemia is characterized by significant reticulocytosis (13.1 +/- 1.0%), anysocytosis, poikilocytosis, iron deficiency and marked alterations of antioxidant and metabolic status of red blood cells. Activities of SOD, catalase, GPx and GR were significantly increased in red blood cells of cadmium-treated rats. In treated animals cadmium induced an increase of red cell reduced and oxidized glutathione with no changes of GSSG/GSH ratio. However, significant reduction of lipid peroxidation was found. Plasma levels of tocopherol and ascorbate, as well as activity of glutathione-S-transferase, were all significantly increased in cadmium-treated rats. The energy metabolism of red blood cells was deeply altered in cadmium-treated rats. The levels of ATP, ADP, AMP and TAN were significantly increased while ATP/ADP ratio and adenylate energy charge (AEC) were significantly reduced. The level of 2,3-BPG was somewhat lower, but 2,3-BPG/Hb ratio was considerably higher, in red blood cells of cadmium-treated rats.
 ...
PMID:Cadmium-induced changes of antioxidant and metabolic status in red blood cells of rats: in vivo effects. 837 Apr 23

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.
 ...
PMID:Effect of chronic uraemia on skeletal muscle metabolism in man. 838 87

The effect of uremia on skeletal muscle metabolism of the rat was examined using 31P-magnetic resonance spectroscopy. Three weeks following either a 5/6 nephrectomy or a sham operation, Wistar rats were placed in a 7T magnet, and the sciatic nerve was stimulated for 10 min. Analysis of spectra allowed calculation of intracellular pH and the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP. [ADP] was calculated from the creatine kinase equilibrium. There was a significant reduction in the resting intracellular [Pi] despite an elevation in extracellular [Pi], probably due to a reduction in the activity of the membrane Na/Pi cotransporter on account of a reduced sodium gradient. Despite anemia and uremia, there were no significant metabolic abnormalities during exercise and recovery accompanying this substantial reduction in glomerular filtration rate implying that at this level of renal impairment, there is no mitochondrial dysfunction.
 ...
PMID:Skeletal muscle metabolism in uremic rats: a 31P-magnetic resonance study. 844 72

Recombinant human erythropoietin (rHuEpo) is now well established in the management of the anaemia associated with chronic renal failure. The aim of this study was to assess the efficacy and safety of low doses of subcutaneous (s.c.) erythropoietin in continuous ambulatory peritoneal dialysis (CAPD) patients and particularly its effects on haemostasis. Seven CAPD patients were given s.c. erythropoietin for more than 1 year. Their mean age was 36.2 +/- 9.2 years and their mean pretreatment haemoglobin (Hb) was 7.05 +/- 0.53 g/dl. All patients were started on 20 U/kg, 3 times/week, to be doubled every 4 weeks if no response was obtained. Five patients had a good response and attained the target Hb of 10-12 g/dl and were maintained on low doses of rHuEpo (20 U/kg s.c., twice a week). A marked improvement in haemostatic function was noted when comparing the pre- with the post-treatment measurements. There was a significant reduction in the bleeding time, significant increases in fibrinogen and factor VIII clotting activity but not in von Willebrand factor antigen or ristocetin cofactor. There was also simultaneous enhancement of the platelet aggregation responses to adrenalin, collagen, arachidonic acid and ADP. In conclusion, long-term treatment with small doses of s.c. rHuEpo is safe, convenient and effective in correcting anaemia in patients on CAPD, rHuEpo caused significant improvement of bleeding time which can be explained partly through the correction of anaemia and in part by the improvement in haemostatic function.
 ...
PMID:One-year experience of very low doses of subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis and its effect on haemostasis. 858 21

Erythropoietin treatment is known to correct anemia and to improve hemostasis. Since platelets may contribute to thromboembolic complications, we assessed platelet aggregation in whole blood and platelet-rich plasma from chronically hemodialyzed patients treated with erythropoietin and evaluated in vitro effects of this drug on aggregatory responses of uremic and normal platelets. Recombinant human erythropoietin was given to uremic patients at a dose of 2,000 IU subcutaneously three times a week. Platelet aggregation in whole blood and platelet-rich plasma was induced by collagen, ADP, arachidonic acid, and ristocetin. In uremic patients, erythropoietin therapy resulted in an enhancement of platelet sensitivity to various agonists, particularly in platelet-rich plasma, reaching values comparable to those of healthy volunteers. In vitro studies we were unable to show any direct effect of erythropoietin, used at concentrations that occurred post intravenous administration, on platelet aggregation both in whole blood and in platelet-rich plasma.
 ...
PMID:Erythropoietin and uremic platelet aggregation in vivo and in vitro. 890 52

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.
 ...
PMID:Cytopathic hypoxia in sepsis. 924 46

Correction of uremic platelet serotonin (5-HT) storage pool deficiency is one of the very early hemostatic effects of erythropoietin (Epo) therapy. In this work, platelet 5-HT with relation to primary hemostasis was studied in 15 hemodialysis patients treated with Epo for 8 months. Moreover, effects of ketanserin, a blocker of platelet and vascular smooth muscle cell 5-HT2A receptors, in these patients were followed. The parameters studied were compared with relevant values in healthy controls and in hemodialysis patients not treated with Epo, and remeasured in the long-term Epo patients after a 14-day oral ketanserin trial. Platelet 5-HT content in the eighth month of Epo therapy was not different from the one in untreated patients. Ristocetin- and collagen-induced platelet aggregation were enhanced in comparison with both control groups, as opposed to unaltered response to ADP and arachidonic acid. Fibrinogen concentration was lower than in the untreated group. An inverse correlation between ADP-induced platelet aggregation and the skin bleeding time (r=-0.536, p<0.05) and a positive one between the former and platelet 5-HT (r=0.644, p<0.01) were found. Platelet count correlated positively with both platelet 5-HT (r=0.823, p<0.0002) and ADP-induced platelet aggregation (r=0.596, p<0.02). Ketanserin produced a decrease in ristocetin-induced platelet aggregation, fibrinogen, and prolongation of the bleeding time. The first two of the changes correlated positively with their pre-ketanserin values (r=0.923, p<0.00001 and r=0.839, p< 0.0001, respectively). Post-ketanserin, positive correlations between depressed ristocetin- and arachidonic acid-induced platelet aggregation (r=0.760, p<0.005), and between collagen- and corresponding values of arachidonic acid- (r=0.622, p<0.02), ADP-induced platelet aggregation (r=0.396, p<0.01), and platelet 5-HT (r=0.654, p<0.05) were found. Efficient hemostasis in hemodialysis patients on protracted Epo therapy is, in part, dependent on enhanced platelet aggregability. Correction of platelet 5-HT storage pool deficiency is not evident in this stage but 5-HT still influences complex mechanisms of primary hemostasis. Ketanserin is of anticoagulant value in these patients but its effects must be weighted against possible exacerbation of the anemia.
 ...
PMID:Long-term effects of erythropoietin on platelet serotonin storage and platelet aggregation in hemodialysis patients with reference to ketanserin treatment. 969 16


<< Previous 1 2 3 4 5 Next >>