Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of recombinant human erythropoietin (rEPO) on angina pectoris in patients with chronic maintenance hemodialysis. We evaluated hemodynamic changes and exercise tolerance in 6 patients underwent symptom-limited treadmill exercise tests, before and 3-months after treatment with rEPO. Hemoglobin concentration and hematocrit increased significantly from 8.1 +/- 1.0 to 10.3 +/- 1.1 g/dl, from 25.7 +/- 2.7 to 31.5 +/- 2.5%, respectively. Exercise duration increased significantly from 291 +/- 68 to 396 +/- 77 sec. Maximal oxygen uptake (VO2max) also increased significantly from 18.3 +/- 3.3 to 24.2 +/- 3.4 ml/kg/min during correction of anemia. Systolic blood pressure (SBP) and pressure rate product (PRP) at rest, and at maximal exercise showed no significant changes, on the other hand ischemic ST change at maximal exercise decreased significantly from 1.2 +/- 0.7 to 0.2 +/- 0.3 mm under 3-months treatment. Our results suggest that improvement of exercise capacity and ST depression in patients with chronic hemodialysis is the outcome of increased coronary oxygen supply with unchanged cardiac oxygen demand after correction of renal anemia treated with rEPO.
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PMID:[Effect of recombinant human erythropoietin (rEPO) on angina pectoris in patients with chronic maintenance hemodialysis]. 187 59

Retrospective studies have provided indirect evidence that allogeneic blood transfusion may adversely influence the prognosis of cancer patients. This effect may be prevented by using autologous blood transfusions. However, this involves preoperative donation of blood, the consequences of which are still unknown. The aim of the present study was to investigate the possible effects of blood loss on tumour growth and on NK-cell activity. An artificial lung metastasis model was used in the BN rat from which 20 per cent of the blood volume was taken at different time intervals. The results showed that blood loss, one day prior to tumour challenge, had a profound stimulating effect on tumour growth. After blood loss, the number of lung metastases was doubled as compared to controls. This tumour-promoting effect could be prevented by an immediate plasma transfusion, but not by evoking a normal haemoglobin level after blood loss by pretreatment with recombinant erythropoietin (rEpo). The NK-cell activity of spleen cells was significantly depressed, 24 hours after blood loss. At a 50:1-lymphocyte-to-target cell ratio, the NK-cell activity dropped from 25.3 per cent in controls to 9.3 per cent in experimental animals. Since NK-cells are assumed to play a role in the clearance of tumour cells from the circulation, the enhanced tumour growth observed after blood loss might be caused by this depression.
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PMID:The influence of blood loss on tumour growth: effect and mechanism in an experimental model. 194 94

The long-term cardiorespiratory effects of recombinant human erythropoietin treatment were investigated in ten haemodialysis patients by means of maximum exercise testing, lung function tests, echocardiography, chest X-ray, and rheological assessment over 12 months. There were significant rises in exercise time (mean [SD] 13.2 [5.5] to 20.0 [6.2] min), maximum oxygen consumption (19.1 [7.0] to 25.0 [6.7] ml.min-1.kg-1), and anaerobic threshold (11.7 [3.6] to 15.4 [4.8] ml.min-1.kg-1) after 2 months of erythropoietin treatment. The improvements were maintained but not augmented on repeat testing after 4, 8, and 12 months of therapy. Carbon monoxide transfer [corrected] rose from 15.5 (2.9) to 18.6 (3.7) ml.min-1.mm Hg-1. There was a substantial reduction in exercise-induced cardiac ischaemia (eight patients had significant ST segment depression before erythropoietin, only one after 2 months' treatment, and none after 12 months' treatment), despite a significant rise in whole blood viscosity. Left ventricular mass, as estimated by echocardiography, progressively decreased from 354 (169) g to 251 (95) g after 12 months' treatment, and four patients showed a reduction in cardiothoracic ratio on chest X-ray.
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PMID:Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. 196 26

Adult female Wistar rats were injected with 125 mg/kg b.w. of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (HMARF). Eleven days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of HMARF. Evaluation of renal function, histopathology studies, and determinations of plasma and kidney erythropoietin (Epo) titers by radioimmunoassay in normoxic and hypoxic conditions were performed 1, 2, 3, 5 and 10 days after M-Hb administration. Treatment induced transient increases in plasma urea concentration, fractional sodium excretion, and urine volume, and significant depression in urine osmolality. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection, and observed on the 5th post-injection day. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. Treatment with M-Hb depressed Epo titers in both kidney homogenates and plasma in normoxic as well as hypoxic rats. Here again, the effect of the first injection of the drug was higher than that of the second one. These observations indicate that there is a negative correlation between kidney tubule injury and Epo production in normoxic and hypoxic conditions. The findings give support to the concept that Epo production is related to proximal tubular function.
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PMID:Depressed plasma erythropoietin levels in rats with hemodynamically-mediated acute renal failure. 209 64

With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells.
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PMID:The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate. 273 90

Adult female Wistar rats were injected with 1 mg/kg body weight of uranyl nitrate (UN). Evaluation of renal function, histopathology studies, and determination of plasma erythropoietin (Ep) titers after exposure to 456 mb for 16 h were performed at 1, 2, 7, 10, 15, and 21 days after drug injection. Plasma urea and creatinine concentrations markedly increased during the first seven days after injection, reaching maximal values on day 7 and decreasing thereafter. Significant increases in urine volume and significant depressions in urine osmolality also were observed; both alterations were most marked on day 7 after injection. A coagulative necrosis of the epithelium of proximal convoluted tubules, desquamation of the necrotic cells, and dilation or collapse of the tubular lumen were observed; the lesions were more marked on day 7. Plasma Ep levels in UN-treated rats exposed to hypobaria were markedly lower than in noninjected controls similarly exposed. Measurements were performed one, two, and seven days after UN injection, with maximal depression observed on day 7. These observations indicate that there is a correlation between the extent of both tubule damage and degree of renal dysfunction and plasma Ep production during exposure to hypoxia in UN-treated rats. This suggests that the renal Ep component is derived primarily from tubular cells.
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PMID:Relationship between severity of renal damage and erythropoietin production in uranyl nitrate-induced acute renal failure. 369 9

The time-response curve for RBC-59Fe uptake following i.p. injections of 3 doses of 5 mg of acetylsalicylic acid (ASA) at 4 hour interval into normal, nonpolycythemic mice, shows a maximal depression (35% of normal) at 3 days after ASA with return to almost normal values by 7 days. The effect is dose-related, showing a plateau with doses of ASA above 5 mg/4 hr. The shape of the time-response curve indicates that the more mature cells in the erythron are not affected by ASA and that the major effect of the drug must be on earlier erythroid cells. Administration of ASA prior to administration of erythropoietin (Epo) into post-hypoxic polycythemic mice depresses the incorporation of 59Fe into erythrocytes. The depression of radioiron uptake is similar when ASA is given prior to or simultaneously with Epo. When ASA is given 24 hr after injection of Epo, suppression is less marked. These results suggest a suppressive effect of the drug on the erythropoietin-responsive cells (ERC).
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PMID:Suppressive effect of acetylsalicylic acid on erythropoietin-responsive cells in mice. 624 81

The capability of chronic beta 2-adrenoceptor activation to effectively stimulate erythrocyte production in vivo was investigated in mice which had been treated with the hematopoiesis inhibiting agent busulfan. A relatively low dose (5 mg/kg i.p.) of busulfan produced moderate depression of erythropoiesis 10 days after a single injection, as determined by 59Fe-incorporation into erythrocytes. Administration of albuterol (1 mg/kg s.c. twice daily), a selective beta 2-adrenergic agonist, significantly enhanced erythropoiesis for 5--10 days after the injection of busulfan. In a long-term study with albuterol at the same dose a significant increase in hematocrit values as well as in the circulating erythrocyte mass was found in busulfan (5 mg/kg i.p. weekly) treated mice when compared to saline-busulfan treated control mice. Simultaneous injections of the beta-adrenergic blocking agent propanolol (4 mg/kg i.p.) diminished the effect of albuterol on erythropoiesis. Albuterol at a lower dose (0.1 mg/kg) had no significant effect on erythrocyte mass. In view of recent findings, which have shown that the proliferation of the pluripotent hemopoietic stem cell pool is blocked by busulfan, it is concluded that the main site of beta 2-adrenergic action on erythropoiesis is on the erythroid committed stem cell pool. In addition, enhanced release of erythropoietin from the kidney following the application of albuterol may contribute to beta 2-adrenergic stimulation of erythropoiesis.
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PMID:beta 2-Adrenergic stimulation of erythropoiesis in busulfan treated mice. 720 79

Plethoric mice treated with pharmacological doses of estradiol have decreased concentration of erythropoietin-responsive cells (ERC) in the marrow. We used the methylcellulose-culture system for growth of erythroid stem cells (CFU-E and BFU-E) to define more accurately these estrogen-induced changes. As an animal model we utilized plethoric mice given repeated injections of estradiol cypionate and found that at 14 days after the onset of treatment there was no significant change in the concentration of femoral CFU-E whereas there was a significant decrease of the BFU-E content. Both CFU-E and BFU-E increased progressively in the spleen over a 42-day period. Addition of estradiol directly to the cell-culture system showed no effect on CFU-E growth but induced a significant depression of BFU-E growth. This depression seemed to require the presence of adherent cells. It is our hypothesis that estrogens suppress only the early stages of erythroid proliferation and/or differentiation by a mechanism involving possibly the stromal (adherent) cells of the marrow microenvironment.
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PMID:The effect of estrogens on erythroid stem cells in polycythemic mice. 732 99

The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.
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PMID:Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients. 770 49


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