losartan-potassium and Starvation

The present study was performed to determine the stage of the erythropoietic pathway which is affected by starvation or protein deprivation and whose manifestation is a depressed response to exogenous erythropoietin (EPO). The response to recombinant human EPO was measured in post-hypoxic polycythemic mice by determination of 59Fe uptake into red cells, spleen and femur and/or erythroid colony forming units (CFU-E) and erythroid precursor cell concentrations in femoral marrow. Experimental mice were either starved or fed one of seven different diets whose protein (casein) content ranged from 0 to 20%. All diets were isocaloric. The response of mice maintained on the standard diet (Purina Lab chow) was taken as the normal one. Starvation during the 48-hour period immediately before EPO injection had no effect on the response to the hormone. Starvation, and protein deprivation to a lesser extent, during the 48-hour period following EPO, on the other hand, significantly reduced the response. There was a progressive increase in the response as the casein content of the diet was increased. A normal response was observed when dietary casein concentration was 10%. These findings indicate that nutritional deprivation or dietary protein alterations during the period immediately following EPO injection in polycythemic mice can have detrimental effects on the erythroid response in a model in which nutritional deprivation was relatively short and acute. They also indicate that the subnormal response is not due to a decreased size of the erythroid progenitor pool available for differentiation but to deficient rates of differentiation of erythropoietic units.

Topics: Animals; Caseins; Dietary Proteins; Drug Resistance; Erythrocyte Count; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Humans; Iron; Mice; Polycythemia; Protein Deficiency; Recombinant Proteins; Reticulocytes; Starvation

Erythropoietic responses of fed and starved species of teleosts, viz., Clarias batrachus and Heteropneustes fossilis, to human urinary erythropoietin and thyroxine have been examined. The effects of these hormones on energy reserves have also been evaluated. Twenty-four C. batrachus were divided into two groups: half were fed regularly; the remaining fish were starved 20 days. On the 21st day each group was further divided into three subgroups of four each and received either saline, thyroxine (8 micrograms), or erythropoietin (6 IU) over 4 consecutive days. The experimental protocol was identical for H. fossilis; however, for H. fossilis two identical studies were conducted approximately 1 year apart. A decline in the rate of erythropoiesis and a stimulatory response to human urinary erythropoietin followed starvation in both species of teleosts. In addition, erythropoietin had a pronounced effect on hepatic glycogenesis of fed H. fossilis and stimulated erythropoiesis in the fed teleosts of both species. Prolonged starvation drastically depleted hepatic glycogen in C. batrachus. In contrast, it had no effect on hepatic glycogen in H. fossilis and on muscle glycogen and protein in both species. In general, while both species could respond to erythropoietin and withstand prolonged starvation, H. fossilis alone exhibited remarkable tolerance to fasting.

Topics: Animals; Energy Metabolism; Erythrocyte Count; Erythropoietin; Fish Diseases; Fishes; Food; Glycogen; Hematocrit; Hemoglobins; Liver Glycogen; Muscle Proteins; Muscles; Starvation; Thyroxine

Starved animals having low levels of erythropoietin in blood showed increased MDA, fluorescent pigments, and met-Hb values whereas the hemoglobin concentration decreased significantly on starvation. In vivo and in vitro studies with Ep reversed the effects of starvation and brought these values close to normal. The activities of the enzymes (SOD, catalase, GSH-PX, GR G6PD, and 6PGD) which protect the RBC membrane directly or indirectly from peroxidative threat, decreased on starvation and restored to normal levels after Ep treatment.

Topics: Animals; Catalase; Erythrocyte Membrane; Erythrocytes; Erythropoietin; Glutathione Peroxidase; Kinetics; Lipid Peroxidation; Membrane Lipids; Microscopy, Electron; Rats; Reference Values; Starvation; Superoxide Dismutase

The effect of Ep on different ATPases and acetylcholinesterase of rat RBC membrane was studied. Starvation caused a slight decrease in Mg2+-, Ca2+-, and Na+ + K+-ATPases. However, these enzyme activities were markedly increased on Ep treatment of starved rats. Specific activities of all three ATPases increased linearly with increasing concentration of Ep. Under identical conditions the hormone failed to stimulate the ATPase activity of liver plasma membrane. Desensitization by fluoride of allosteric inhibition of erythrocyte membrane-bound Na+ + K+-ATPase was observed under starvation which showed a return to normal n values on Ep administration. The enzyme from normal animals was inhibited almost completely at 0.1 mM fluoride whereas enzyme from starved and Ep-treated animals showed only about 50% inhibition at that fluoride concentration. Ep increased the acetylcholinesterase activity of normal RBC membrane to a small extent whereas the stimulation was much higher under starvation. The fluoride inhibition curve of this enzyme changed from sigmoidal to hyperbolic under starvation which again changed to allosteric on administration of Ep. These changes were closely correlated to n values. Red blood cells of Ep-treated animals became more susceptible to osmotic shock under the experimental conditions.

Topics: Acetylcholinesterase; Adenosine Triphosphatases; Animals; Ca(2+) Mg(2+)-ATPase; Calcium-Transporting ATPases; Erythrocyte Membrane; Erythropoietin; Fluorides; Osmotic Fragility; Rats; Sodium-Potassium-Exchanging ATPase; Starvation

Effect of Ep on [14C]acetate incorporation into different lipid fractions of RBC membranes in starved and phenylhydrazine-treated rats was studied. The incorporation was increased into both neutral and phospholipid fractions on Ep treatment to starved or phenylhydrazine-treated rats. A slight decrease in the ratio of neutral lipid to phospholipid was observed under the influence of Ep in starved rats (23%) or in phenylhydrazine-treated rats (36%). Incorporation of radioactivities into different phospholipid fractions of RBC membrane increased on Ep treatment to starved rats, whereas, the relative percentages of these phospholipids (except LPC) remained more or less unchanged under similar conditions. Phenylhydrazine treatment increased the relative percentage of PC and concomitantly decreased the percentage of Sph. Percentage composition of both these two phospholipids showed a tendency to return to their normal levels on administration of Ep to phenylhydrazine-treated rats. Ep decreased the sigma saturated/sigma unsaturated ratio of fatty acids in PE, PS, and PC of RBC membrane in starved rats. On the other hand, no significant change was observed in this ratio of fatty acids in the phospholipids except Sph of RBC membrane in the presence of phenylhydrazine and Ep. In Sph, the ratio went down under similar conditions.

Topics: Acetates; Animals; Chemical Phenomena; Chemistry; Cholesterol; Erythrocyte Membrane; Erythropoietin; Fatty Acids; Fatty Acids, Unsaturated; Membrane Lipids; Phenylhydrazines; Phospholipids; Rats; Starvation

The erythropoietic response of snakes was examined after injecting human urinary erythropoietin (Ep), testosterone propionate (TP), and L-thyroxine (T4), separately and in combinations, into starved ophids. The effect of starvation was reflected by a decrease in the number of erythrocytes, a fall in hemoglobin concentration, and a decline in hematocrit. Statistically significant elevation of erythrocyte number, hemoglobin concentration, and hematocrit was observed at 24 hr following the administration of Ep + T4, and Ep + TP + T4 into starved ophids. The erythrocyte number was also increased by T4 treatment at 24 hr. Furthermore, while T4 and Ep individually increased the red blood cell number at 168 hr, T4, TP + T4, and Ep + TP + T4 elevated the hemoglobin concentration and Ep + T4 and Ep + TP + T4 increased the hematocrit value. It is suggested that the influence of any one of the hormones utilized in the present study on blood morphology of fasted snakes depends to a greater extent on the presence or absence of the other hormone(s).

Topics: Animals; Erythrocyte Count; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobins; Humans; Snakes; Starvation; Testosterone; Thyroxine

Topics: Acetates; Animals; Erythrocyte Membrane; Erythrocytes; Erythropoietin; Kinetics; Lipids; Phenylhydrazines; Rats; Reticulocytes; Sheep; Starvation

Radioiron uptake by erythrocytes, metabolic rate, erythropoietin formation during hypoxia and erythroid responsiveness to exogenous erythropoietin were determined in both starved and water deprived rats. The feed intake showed a marked and progressive reduction during water deprivation. The metabolic rates of rats deprived of either food of water declined progressively showing a 40% reduction 5d after water deprivation or starvation began. At this time, the 24 h red blood cells 59Fe incorporation was 85% lower in both starved and dehydrated rats than in normal rats. Plasma erythropoietin levels in response to hypoxia were approximately 50% decreased in both starved and dehydrated rats. Both polycythaemic starved and polycythaemic water deprived rats injected with human urinary erythropoietin showed a 75% decrease in 59Fe incorporation into erythrocytes when compared to control rats. It is suggested that depression of erythropoiesis during water deprivation in the rat depends on a reduced sensitivity to erythropoietin, possibly associated with decreased production of the hormone. Since water deprived rats drastically reduce feed intake it is suggested that secondary starvation is the principal cause of the decreased erythropoiesis induced in the rat by water deprivation.

Topics: Animals; Dehydration; Energy Metabolism; Erythropoiesis; Erythropoietin; Female; Hypoxia; Male; Polycythemia; Rats; Starvation; Water Deprivation

Topics: Animals; Caseins; Dietary Proteins; Egg Yolk; Erythrocytes; Erythropoietin; Female; Glutens; Iron; Male; Polycythemia; Protein Deficiency; Rats; Starvation; Zea mays

Mammalian erythropoiesis is regulated primarily by the hormone erythropoietin (ESP). Studies of ESF have provided information about its biochemistry and its role in regulating hemoglobin synthesis. Such studies rely on assays for erythropoietic activity in biological fluid. The assay which has proven most valuable and is used most widely is based upon the incorporation of radioactive iron into newly-formed red cells of polycythemic mice. While this assay has gained wide acceptance, it is expensive, cumbersome, imprecise, and insensitive, capable of reliably detecting no less than 50 milliunits of erythropoietin. Improvements in assay techniques will require new methodology relying primarily on immunologic recognition for the determination of hormone activity. Currently under development and in experimental use are radioimmunoassays and a hemagglutination inhibition assay. While work has progressed in these areas, these assays are not of proven value at present and meaningful physiological correlations have not emerged from their use. Alternatively, assays for hormone activity using suspensions of hematopoietic cells and the measurement of incorporation of radioactive isotopes into hemoglobin have provided both improvement in sensitivity and precision. The disadvantage of these types of assays is that they are sensitive to factors other than ESF and may give misleading information, depending on whether the factors present stimulate or inhibit cellular proliferation and hemoglobin synthesis. While such techniques may provide a temporary solution to some problems associated with assaying ESF for purification or physiological studies, they are not the best answer to the overall problem of hormone detection and characterization. The most important contribution to this field will be the availability of large amounts of highly purified and well-characterized ESF.

Topics: DNA; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Hypophysectomy; Iron; Phosphates; Polycythemia; Starvation

Topics: Animals; Biological Assay; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Erythropoietin; Fetus; Hemoglobins; Iron; Liver; Methods; Mice; Polycythemia; Protein Binding; Rats; Spleen; Starvation; Time Factors

Topics: Animals; Erythrocytes; Erythropoiesis; Erythropoietin; Hypoxia; Iron; Iron Radioisotopes; Polycythemia; Rats; Starvation

Topics: Anemia; Animals; Antigen-Antibody Reactions; Biological Assay; Chromatography, DEAE-Cellulose; Chromatography, Gel; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Erythropoietin; Humans; Hydrogen-Ion Concentration; Iron; Iron Radioisotopes; Mathematics; Rats; Sodium Dodecyl Sulfate; Spectrophotometry, Ultraviolet; Starvation; Urea

Topics: Animals; Cobalt; Cobalt Isotopes; Enzyme Induction; Erythrocytes; Erythropoietin; Iron; Iron Isotopes; Kidney; Male; Mice; Monoiodotyrosine; Neuraminidase; Peroxidases; Rats; Sheep; Starvation; Submandibular Gland; Thyroid Gland; Vitamin B 12

Topics: Amino Acids; Anemia; Animals; Biological Assay; Blood Protein Electrophoresis; Carbohydrates; Chromatography, Gel; Electrophoresis, Disc; Erythrocytes; Erythropoietin; Glycoproteins; Humans; Hydrogen-Ion Concentration; Immunodiffusion; Iron; Iron Isotopes; Rats; Spectrophotometry, Ultraviolet; Starvation

Topics: Adrenocorticotropic Hormone; Animals; Drug Synergism; Erythropoiesis; Erythropoietin; Female; Hydrocortisone; Hypoxia; Immune Sera; Iron Isotopes; Mice; Polycythemia; Starvation; Stimulation, Chemical; Testosterone; Thyroxine; Triiodothyronine

Topics: Ammonium Sulfate; Animals; Antibody Formation; Antigen-Antibody Complex; Antigen-Antibody Reactions; Biological Assay; Chemical Precipitation; Erythrocytes; Erythropoietin; Humans; Hydrogen-Ion Concentration; Immune Sera; Immunization; Immunodiffusion; Iron; Iron Isotopes; Kinetics; Rabbits; Rats; Starvation; Temperature

Topics: Anemia; Animals; Atmospheric Pressure; Blood Volume; Dehydration; Erythrocytes; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Polycythemia; Rats; Starvation

Topics: Animals; Blood Volume; Erythropoiesis; Erythropoietin; Fishes; Iron Isotopes; Starvation

Topics: Anemia, Aplastic; Animals; Atmospheric Pressure; Biological Assay; Blood Cells; Bone Marrow; Bone Marrow Cells; Dactinomycin; Erythropoiesis; Erythropoietin; Hematocrit; Iron Isotopes; Methods; Mice; Nitrogen Mustard Compounds; Oxygen; Phenylhydrazines; Polycythemia; Rats; Starvation

Topics: Animals; Animals, Laboratory; Biological Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Iron; Iron Isotopes; Mice; Polycythemia; Rabbits; Rats; Starvation; World Health Organization

Topics: Animals; Biological Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hypoxia; Iron; Iron Isotopes; Kidney; Male; Mice; Mutation; Nandrolone; Nephrectomy; Polycythemia; Sex Factors; Starvation; Testosterone; Ureter

Topics: Animals; Animals, Newborn; Bone Marrow; Bone Marrow Cells; Erythropoiesis; Erythropoietin; Female; Fetus; Guinea Pigs; Humans; Infant, Newborn; Nephrectomy; Pregnancy; Rats; Starvation

Topics: Animals; Biological Assay; Blood; Epoetin Alfa; Erythropoietin; Hypophysectomy; Mice; Plasma; Polycythemia; Starvation

Topics: Androgens; Animals; Basal Metabolism; Drug Synergism; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Iron; Iron Isotopes; Mice; Nandrolone; Pharmacology; Polycythemia; Research; Starvation; Testosterone; Triiodothyronine

Topics: Animals; Biological Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Rats; Starvation

Topics: Animals; Blood Cell Count; Blood Volume; Bloodletting; Erythropoiesis; Erythropoietin; Iron Isotopes; Reptiles; Starvation

Topics: Animals; Biological Assay; Dogs; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypophysectomy; Plasma; Polycythemia; Rats; Research; Starvation; Thyroidectomy

Topics: Blood; Bone Marrow; Epoetin Alfa; Erythropoietin; Intestinal Absorption; Iron; Kidney; Liver; Pharmacology; Rats; Research; Spleen; Starvation

Topics: Anemia; Biological Assay; Cobalt; Epoetin Alfa; Erythropoietin; Humans; Hypophysectomy; Hypoxia; Oxygen; Starvation

Topics: Animals; Cobalt; Epoetin Alfa; Erythrocytes; Erythropoietin; Iron; Nephrectomy; Rats; Sheep; Starvation

Topics: Epoetin Alfa; Erythropoietin; Iron Isotopes; Rats; Research; Starvation

Topics: Animals; Epoetin Alfa; Erythropoietin; Rats; Reticulocytes; Starvation

Topics: Animals; Epoetin Alfa; Erythropoiesis; Erythropoietin; Protein Deficiency; Proteins; Rats; Research; Starvation

Topics: Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Polycythemia; Rats; Starvation