Urinary elimination of erythropoietin in patients under treatment with cytostatics drugs.

Reductions in the hemoglobin (Hb) mass are followed by increases in the level of plasma erythropoietin (EPO) concentrations which are directly proportional to the level of the hormone required to bring the hemoglobin values back to normalcy. Hypoplastic anemias (AHC) on the other hand, are accompanied by significantly larger increases in the erythropoietin concentration. In this study we have measured the relationship between the severity of the anemia and the levels of erythropoietin elimination in the urine patients (EpoU) under treatment with cytostatic drugs. Simultaneously other parameters used as indicators of bone marrow activity were determined. These observations suggest that the levels of erythropoietin depends not only by the tissue oxygen availability but by others factors related to the marrow cellularity.

Urinary elimination of erythropoietin in patients under treatment with cytostatics drugs

La reducción de la masa de hemoglobina (Hb) que ocurre en las anemias aumenta la producción de eritropoyetina (EPO) en una proporción conmensurada con el nivel de estímulo eritropoyético necesario para reponer la normalidad de la dimensión de la masa del pigmento transportador de oxigeno. Las anemias hipoplásticas congénitas (AHC) muestran niveles de Epo plasmática substancialmente mayores que las que se comprueban en anemias en las que no existe esa alteración medular. En este estudio hemos medido los niveles de Epo eliminada por orina (EpoU) en pacientes bajo tratamiento con drogas citostáticas (DC). Simultáneamente se determinaron otros parámetros hemáticos utilizados corrientemente como indicadores de la actividad medular. Nuestras observaciones sugieren que existen otros factores involucrados en la produccion de Epo además de la hipoxia tisular, los que estarían probablemente relacionados a la celularidad medular. (AU)

Urinary elimination of erythropoietin in patients under treatment with cytostatics drugs

La reducción de la masa de hemoglobina (Hb) que ocurre en las anemias aumenta la producción de eritropoyetina (EPO) en una proporción conmensurada con el nivel de estímulo eritropoyético necesario para reponer la normalidad de la dimensión de la masa del pigmento transportador de oxigeno. Las anemias hipoplásticas congénitas (AHC) muestran niveles de Epo plasmática substancialmente mayores que las que se comprueban en anemias en las que no existe esa alteración medular. En este estudio hemos medido los niveles de Epo eliminada por orina (EpoU) en pacientes bajo tratamiento con drogas citostáticas (DC). Simultáneamente se determinaron otros parámetros hemáticos utilizados corrientemente como indicadores de la actividad medular. Nuestras observaciones sugieren que existen otros factores involucrados en la produccion de Epo además de la hipoxia tisular, los que estarían probablemente relacionados a la celularidad medular.

A new approach to the etiopathogenesis of AIDS.

This hypothesis proposes as an explanation for the origin of the Acquired Immuno-Deficiency Syndrome (AIDS), the homosexual transmission of spermatozoons. The male gamete may possess a depressing action on the immuno-competence of the egg aimed to prevent the rejection of the spermatozoon material. The female organism may be able to inactivate this action, an ability that might be absent in the male organism. As a consequence of the loss of its immunological competence, the body is invaded by a variety of microorganisms, among which certain elemental classes of viruses would strive successfully for long periods of time. Their permanence in the depressed organism would enable them to overcome the immune barriers present in normal subjects, becoming thus, transmissible and in some cases even pathogenic for the new host.

[Ability of the Fe-transferring complex to transfer Fe to reticulocytes in nutritional anemia]. / Aptitud del complejo Fe/transferrina para transferir Fe a los reticulocitos en la anemia nutricional.

Using an in vitro technique the ability of the Fe/Transferrin complex in the serum of calories and proteins in chronically deprived adult males was investigated. The study included the behavior of the same function in the sera of other types of anemias. A significant reduction of the Fe donating capacity was found in the sera of patients suffering from nutritional anemia (NA), whereas this change was absent in the sera of other type of anemias. A deterioration of the iron donating function of the Fe/Transferrin complex caused by malnutrition, is postulated. The participation of this alteration in the production of NA is considered.

Relationship between erythropoietic rate and iron donating capacity of the Fe/transferrin complex in mouse.

The transfer of iron from the Fe/transferrin complex to the erythroid cells was studied in in vitro system in mice in which a drastic and opposite change in their erythropoietic activity was produced by bleeding or actinomycin D administration. A reduction of iron donation in the serum of bled animals was found, whereas the aplastic condition induce in the donors of the serum by actinomycin D did not produce any change in the transfer process. It was also found that in spite of the normalization of the saturation in the serum of bled animals, the diminished donation remained unchanged. The possibility that conditions other than quantitative could produce this behavior is discussed.

[Trophic effect of testosterone on erythropoiesis in the mouse]. / Acción trófica de la testosterona sobre la eritropoyesis del ratón.

Some differences between erythropoietin biogenesis under the action of natural stimuli and that resulting from testosterone administration are commented. Evidences are presented suggesting that androgens, apart from amplifying erythropoietin production, might exert some action on the stroma as specific erythrocytic tissue. This action could be anabolic or trophic and not erythropoietin dependent, at least to some extent, its effect being applied on the quantitative erythropoietic homeostasis.

A simple method for concentrating erythropoietin activity in plasma and in other body fluids.

The method here described is based on the property of erythropoietin to remain in water solution in the presence of up to 60% ethanol. More than 90% of inert proteins precipitate in the process and can be eliminated without significant loss of the activity. The addition of sulfuric ether produces the separation of the water phase and of its solutes which can be recovered in the solid material obtained by lyophilization. Using this method a marked erythropoietin activity can be demonstrated in extracts of the plasma from mice with a moderate reduction of the hematocrit.

A simple method for concentrating erythropoietin activity in plasma and in other body fluids.

The method here described is based on the property of erythropoietin to remain in water solution in the presence of up to 60

ethanol. More than 90

of inert proteins precipitate in the process and can be eliminated without significant loss of the activity. The addition of sulfuric ether produces the separation of the water phase and of its solutes which can be recovered in the solid material obtained by lyophilization. Using this method a marked erythropoietin activity can be demonstrated in extracts of the plasma from mice with a moderate reduction of the hematocrit.

A bioassay method for studying factors stimulating erythropoiesis using as recipient the mouse with a functionally active erythron.

This novel bioassay method basically differs from the conventional plethoric mouse assay in the timing of the onset of induced polycythemia relative to the administration of the substances that are being tested. While the latter measures the regenerating action of erythropoietin at a time when erythropoiesis is virtually absent, the method here described evaluates the stimulatory action(s) required to maintain the normality of the process. This fact opens new approaches for studying factors involved in the quantitative govern of erythropoiesis in the steady state.

A bioassay method for studying factors stimulating erythropoiesis using as recipient the mouse with a functionally active erythron.

This novel bioassay method basically differs from the conventional plethoric mouse assay in the timing of the onset of induced polycythemia relative to the administration of the substances that are being tested. While the latter measures the regenerating action of erythropoietin at a time when erythropoiesis is virtually absent, the method here described evaluates the stimulatory action(s) required to maintain the normality of the process. This fact opens new approaches for studying factors involved in the quantitative govern of erythropoiesis in the steady state.

Systemic oxygen transport and erythropoiesis in the mouse.

Removal of 15% of blood volume in the mouse increases erythropoiesis by a factor of 2.2 when measured 12 h after bleeding. Exposure of normal mice to 40% reduced barometric pressure for the same period of time increases erythropoiesis only by a factor of 1.6. The response to hypoxia takes place in the presence of a 40% reduction of oxygen consumption and tissue-venous PO2, changes which are concomitant with a 5-fold increase in plasma erythropoietin activity. The larger response in anemic animals on the other hand occurs without any detectable change in these parameters. These results cast serious doubts about the interpretation of the quantitative homeostatic control of erythropoiesis based solely on the action of erythropoietin.

Assay of urinary N-acetyl-beta-glucosaminidase in a centrifugal analyzer.

We describe a kinetic, fluorometric assay for urinary N-acetyl-beta-glucosaminidase (EC 3.2.1.30) by measurement of the release of 4-methylumbelliferone (7-hydroxy-4-methylcoumarin). The method is simple, involving only a single reagent, and is applicable to the assay of other enzymes that hydrolyze similar fluorescent-labeled substrates. The enzyme distribution in human tissues and fluids is described. The enzyme is present in high concentrations in human kidney, liver, and lung. Its concentration in urine is shown to be a sensitive indicator of early renal damage, which precedes changes in serum creatinine and urinary protein. Assay of the enzyme is quite useful in monitoring renal damage due to myoglobinuria.