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1.
Science ; 173(3993): 249-51, 1971 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-5087490

RESUMO

Inborn errors of metabolism often cause epilepsy, as with certain strains of mice. Aggravating the metabolic defect with a protein synthesis inhibitor increases the symptoms. Mature animals that have "outgrown" their genetic susceptibility to audiogenic seizures are made susceptible again by acetoxycycloheximide. After a single small dose the incidence and severity of audiogenic seizures increases at 16 hours, reaches a maximum of 40 hours, and then declines gradually.


Assuntos
Piridonas , Convulsões , Som , Fatores Etários , Animais , Erros Inatos do Metabolismo/complicações , Oxigenases de Função Mista/antagonistas & inibidores , Piridonas/farmacologia , Piridonas/toxicidade , Ratos , Convulsões/induzido quimicamente , Convulsões/complicações , Convulsões/etiologia , Fatores de Tempo
2.
Exp Hematol ; 16(2): 159-62, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3338512

RESUMO

Patients and/or experimental animals with chronic renal failure have decreased serum levels of triiodothyronine (T3), a hormone well known for its erythropoietic activity. The following studies were designed in order to determine whether this observed abnormality in T3 metabolism is an important contributory factor to the etiology of the anemia of uremia. Groups of rats were made chronically uremic by a standard 5/6 nephrectomy technique and received slightly above physiological doses of T3 either by intermittent S.C. injections (twice daily) or by continuous infusion from intraperitoneally implanted osmotic minipumps. After 2 weeks of such treatment, and despite a normalization of serum T3 levels, there were no significant changes in the hematocrit, individual red cell mass, or serum erythropoietin levels of the uremic animals given T3 compared to control rats. We conclude that (1) the decreased serum T3 levels observed in uremia are not an important contributory factor to the pathogenesis of the anemia, and (2) treatment with replacement doses of T3 does not result in significant improvement of erythropoiesis.


Assuntos
Anemia/sangue , Falência Renal Crônica/complicações , Tri-Iodotironina/farmacologia , Anemia/etiologia , Animais , Volume de Eritrócitos , Eritropoetina/sangue , Feminino , Hematócrito , Ratos , Ratos Endogâmicos , Tri-Iodotironina/sangue
3.
Exp Hematol ; 15(7): 785-9, 1987 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3609182

RESUMO

Serum erythropoietin levels were measured by radioimmunoassay and compared to the severity of anemia in patients with end stage renal disease of different etiology, on chronic hemodialysis. It was demonstrated that the difference in severity of anemia in those patients is a consequence of a difference in erythropoietin production, rather than due to a difference in the level of erythropoiesis inhibitors. It was stressed that in patients with polycystic kidney disease the kidney tissue kept its endocrine function although it had no residual excretory renal function. The positive correlation between hematocrit values and erythropoietin levels indicates that in these patients erythropoietin synthesis is not regulated by general hypoxia. It is suggested that control of erythropoietin production in diseased kidney differs from normal physiological control.


Assuntos
Anemia/complicações , Eritropoetina/sangue , Falência Renal Crônica/complicações , Adulto , Anemia/sangue , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Diálise Renal
4.
Exp Hematol ; 13(1): 59-66, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3871703

RESUMO

A two-stage cell culture assay specific for human erythroid burst-promoting activity (BPA) is described. Human peripheral blood mononuclear cells were cultured in suspension with or without a BPA test sample for two days, then transferred to methylcellulose medium with added erythropoietin (EPO) and incubated for ten more days, and finally BFU-E-derived colonies were scored. An increase in number of colonies due to the presence of BPA was observed that was proportional to the concentration of BPA in the test sample. This response was linear with respect to number of cells plated between 2 and 5 X 10(5)/ml. The system was standardized with a partially purified human urinary BPA preparation. Dose responses to urinary protein preparations, plasma, and serum were parallel. The assay system was found to be nonresponsive to highly purified EPO and to bacterial endotoxin. It was determined that BPA action was confined to the suspension culture stage of the assay, while EPO presence was an absolute requirement during methylcellulose culture. In the two-stage assay optimal amounts of BPA caused up to 358% increases of BFU-E-derived colonies; the same amounts of BPA added to conventional methylcellulose cultures caused only up to 54% increases over the number of colonies obtained with EPO alone. Plasma and serum BPA levels of hematologically normal and abnormal individuals showed no correlation with EPO levels and hemoglobin (Hb) concentrations. This seems to rule out the possibility that BPA elaboration is regulated by oxygen availability or the amount of EPO circulating in an organism.


Assuntos
Ensaio de Unidades Formadoras de Colônias , Fatores Estimuladores de Colônias/análise , Eritropoese , Células-Tronco Hematopoéticas/metabolismo , Anemia Aplástica/sangue , Animais , Contagem de Células , Células Cultivadas , Fatores Estimuladores de Colônias/sangue , Fatores Estimuladores de Colônias/fisiologia , Relação Dose-Resposta a Droga , Endotoxinas/farmacologia , Eritropoese/efeitos dos fármacos , Eritropoetina/farmacologia , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Camundongos , Policitemia Vera/sangue
5.
Exp Hematol ; 15(1): 18-23, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3536546

RESUMO

Rat erythropoietin (Ep) cross-reacts in the radioimmunoassay (RIA) for human Ep developed in this laboratory. Immunoreactive Ep was measured in serum and tissues of male rats in response to short-term hypoxia (0.43 atm for 24 h). In the unstimulated rat all tissues examined had low levels of Ep, with the exception of the submaxillary or salivary gland (SG). Exposure to hypoxia for 24 h resulted in significant increases in kidney and serum levels of Ep, with no apparent change in SG content. Sialectomy immediately prior to exposure reduced renal Ep production and serum levels significantly after 4 h of exposure. Nephrectomy (N) confirmed previous results by others: Ep production after exposure to hypoxia was reduced but not abolished. The effect of N plus sialectomy was identical to that of N alone, thus excluding the SG as a source of extrarenal Ep in nephrectomized rats. The long-term effect of SG ablation to the same constant stimulus was a steady decline of the Ep response during the first week after surgery, both in renal production and serum levels. Thereafter, from one to six weeks the serum levels remained constant, being higher than in the unstimulated rat but significantly lower than in intact hypoxic animals. No cross-reactivity in the RIA was found with renin, renin substrate, nerve and epidermal growth factor, or somatomedins. If this Ep-like substance in the SG were the source of extrarenal Ep, it should have been possible to document an increase in serum concentration before an increase could be measured in renal content. It appears, however, that the presence of the SG is necessary for renal tissue to be able to synthesize Ep during hypoxia.


Assuntos
Eritropoetina/metabolismo , Hipóxia/fisiopatologia , Rim/metabolismo , Glândulas Salivares/metabolismo , Animais , Técnicas Imunológicas , Masculino , Ratos , Distribuição Tecidual
6.
Exp Hematol ; 20(3): 350-3, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1348981

RESUMO

We have previously reported the successful development of hematopoietic chimerism after the in utero transplantation of fetal hematopoietic stem cells (HSC) in rhesus monkeys (Macaca mulatta). These animals exhibit sustained engraftment without immunosuppression or graft-versus-host disease (GVHD). To assess the functional response of the donor-derived erythropoietic population, we assayed the relative expression of donor and recipient hematopoietic progenitors in chimeric monkeys before and after anemic stress. Anemia in our chimeric animals resulted in increased erythropoietin (EPO) production comparable to controls. This was accompanied by changes in erythroid progenitor profiles, again similar to controls. Chimeric animals demonstrated normal reticulocytosis and reconstituted their hematocrit after hemorrhage at the same rate as controls. The donor-derived erythropoietic population exhibited normal responses to recipient regulatory signals and did not seem to expand at the expense of other hematopoietic lineages. Thus the proportions of engraftment for the myeloid and erythroid precursors in bone marrow and for blood lymphocytes remained stable. Our results demonstrate that the in utero transplantation of fetal HSC results in stable engraftment of donor erythropoietic progenitors, which appear to be fully integrated within the recipient's regulatory system. The abnormalities reported in the postnatal transplantation setting can then be attributed to immunologic reactions requiring conditioning myeloablative regimens. Fetal transplantation bypasses all these factors.


Assuntos
Quimera/fisiologia , Eritropoese/fisiologia , Transplante de Tecido Fetal/fisiologia , Transplante de Células-Tronco Hematopoéticas , Macaca mulatta/fisiologia , Anemia/sangue , Anemia/patologia , Anemia/fisiopatologia , Animais , Contagem de Células Sanguíneas , Eritropoetina/metabolismo , Feminino , Hematócrito , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/fisiologia , Hemorragia/patologia , Hemorragia/fisiopatologia , Linfócitos/patologia , Linfócitos/fisiologia , Gravidez , Reticulócitos/patologia
7.
Exp Hematol ; 16(11): 950-3, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3181346

RESUMO

Spontaneously hypertensive rats (SH) with an increased number of red blood cells (RBC), microcytosis, and normal hemoglobin (Hb) concentration were used to study the effect of different manipulations of the erythron on erythropoietin production and on erythroid progenitor proliferation by bone marrow cells in order to gain insight regarding the regulation of erythropoiesis. The serum erythropoietin (Ep) level was increased in untreated SH rats. After stimulation by either bleeding, hemolysis, or acute hypoxia, both the erythropoietin level and erythroid colony-forming unit (CFU-E) proliferation by bone marrow cells increased in SH rats to levels that were similar to those of normotensive Wistar (W) rats. Exposure to chronic hypoxia induced an increase in Hb concentration in SH rats concomitantly with the increase in RBC. The results obtained in SH rats raise the possibility of a defect in nonEp stimulators of erythropoiesis that may alter Hb synthesis.


Assuntos
Hemoglobina A/metabolismo , Policitemia/sangue , Ratos Endogâmicos SHR/sangue , Ratos Endogâmicos/sangue , Animais , Medula Óssea/patologia , Ensaio de Unidades Formadoras de Colônias , Eritroblastos/metabolismo , Índices de Eritrócitos , Feminino , Masculino , Ratos
8.
Exp Hematol ; 16(2): 122-4, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3276543

RESUMO

The physiological role of immunoreactive erythropoietin (iEp) in rodent submaxillary glands (SMG) is largely unknown. We studied in vivo the effects of cholinergic and adrenergic agents in male rats with respect to exocrine secretion of iEp into saliva. Intravenous administration of metacholine (20 micrograms/kg), norepinephrine (30 micrograms/kg), and isoproterenol (30 micrograms/kg) resulted in equal volumes of saliva over 1 h. None of the drugs altered circulating plasma levels and kidney concentrations of iEp. Salivary secretions induced by either norepinephrine or isoproterenol, both adrenergic agonists, contained high levels of iEp and a significant depletion of gland content was observed, suggesting that SMG exocrine iEp secretion is mediated by adrenergic receptors. In contrast, metacholine-stimulated glands retained their full iEp content and iEp was undetectable in saliva, indicating that cholinergic activity is not associated with exocrine secretion of iEp from SMGs.


Assuntos
Eritropoetina/metabolismo , Glândula Submandibular/metabolismo , Animais , Eritropoetina/sangue , Isoproterenol/farmacologia , Rim/metabolismo , Masculino , Cloreto de Metacolina , Compostos de Metacolina/farmacologia , Norepinefrina/farmacologia , Radioimunoensaio , Ratos , Ratos Endogâmicos , Saliva/análise
9.
Exp Hematol ; 20(11): 1257-62, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1493855

RESUMO

In this study, the extent to which growth factor production and microenvironment might be responsible for defective erythropoiesis and granulopoiesis in anemic b/b rats is investigated. Radioimmunoassay-determined serum erythropoietin (Epo) levels are high in b/b rats and closely related to degree of anemia. The low number of erythroid progenitors in b/b rats despite a high Epo level suggested that the defective erythropoiesis could be due to a low level of burst-promoting activity (BPA). A pokeweed mitogen-stimulated medium (PWM-SCM) was prepared with b/b rat spleen cells and used in normal and anemic rat bone marrow and spleen cultures to determine BPA and other growth factor levels. No erythroid burst-forming unit-derived colonies were found but granulocyte-macrophage colony-forming units were counted in significant number, suggesting that the production of growth factors that supports the growth of granulopoietic progenitors is not significantly disturbed. Because BPA is produced mainly by T-lymphocytes, the low BPA level in b/b rat PWM-SCM raised the question of the functional capacity of T-lymphocytes. Investigations showed a decrease in the proliferative activity of b/b rat spleen mitogen-activated T-lymphocytes to about 20% of controls as well as a decrease in interleukin-2 activity in b/b rat spleen cell supernatants. These results point to defective T-lymphocytes. A study of bone marrow fibroblastoid cell colonies (CFU-F) revealed significantly lower CFU-F counts in the b/b rats. This finding is indicative of a disturbed microenvironment, which could also to some extent be responsible for decreased growth factor production and depressed hematopoiesis in the b/b rat.


Assuntos
Anemia/metabolismo , Hematopoese , Fatores de Crescimento de Células Hematopoéticas/biossíntese , Anemia/tratamento farmacológico , Anemia/patologia , Animais , Medula Óssea/patologia , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Meios de Cultivo Condicionados , Células Precursoras Eritroides/patologia , Eritropoese , Eritropoetina/metabolismo , Feminino , Granulócitos/patologia , Células-Tronco Hematopoéticas/patologia , Ferro/uso terapêutico , Macrófagos/patologia , Masculino , Mitógenos de Phytolacca americana/farmacologia , Ratos , Ratos Mutantes , Baço/patologia , Linfócitos T/fisiologia
10.
Obstet Gynecol ; 76(2): 219-22, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2371024

RESUMO

The erythropoietin levels in mixed cord serum of 40 infants born to drinking women were compared with those of 24 infants born to abstinent women. Twenty infants born to drinkers had signs of fetal alcohol effects. Thirty-five percent of the erythropoietin levels in mixed cord serum of infants of drinking mothers were above the normal range. Further, the elevation in fetal erythropoietin level correlated with maternal alcohol intake; infants of mothers consuming at least 300 g of ethanol weekly (28) had significantly higher (P less than .025) umbilical erythropoietin levels (median 66 mU/mL, range 10-2500) compared with infants of mothers consuming 150-300 g of ethanol weekly (median 37 mU/mL, range 23-215) or infants of control women (median 32 mU/mL, range 11-73). The subgroup analysis between infants with and without fetal alcohol effects showed no differences in umbilical erythropoietin levels. Maternal alcohol ingestion during pregnancy is associated with elevated umbilical erythropoietin levels, but whether this is a direct effect of ethanol or is induced by chronic fetal hypoxemia remains unclear.


Assuntos
Alcoolismo , Eritropoetina/sangue , Sangue Fetal/análise , Complicações na Gravidez , Adulto , Índice de Apgar , Feminino , Humanos , Recém-Nascido , Troca Materno-Fetal , Gravidez
11.
Obstet Gynecol ; 69(5): 710-6, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3574798

RESUMO

In the human fetus, elevated plasma erythropoietin levels have been found in high-risk pregnancies at delivery. We examined the relationship of amniotic fluid erythropoietin and umbilical plasma erythropoietin at delivery in 17 normal pregnancies, 41 hypertensive pregnancies, and 37 insulin-treated diabetic pregnancies terminated by elective cesarean section without labor. An additional 27 insulin-treated diabetic patients were studied after undergoing variable durations (86-1184 minutes) of labor. Erythropoietin was analyzed using a highly sensitive and specific radioimmunoassay technique. Fetal plasma erythropoietin concentrations were elevated above the control upper range (50.3 mU/mL) in 59% of the hypertensives and in 38% of the diabetics. The amniotic fluid erythropoietin values were significantly lower than the umbilical plasma erythropoietin values in each study group. Although the umbilical plasma erythropoietin values in the abnormal pregnancy groups differed considerably from the corresponding levels in the controls, the ratio of amniotic fluid erythropoietin to umbilical plasma erythropoietin was approximately the same in controls, hypertensives, and diabetics. Furthermore, the plasma and amniotic fluid levels (In transformed) correlated highly significantly in all three individual groups in absence of labor. In the diabetic labor group, this relationship was nonsignificant. We conclude that in the absence of labor, amniotic fluid erythropoietin reflects fetal plasma erythropoietin. We speculate that amniotic fluid erythropoietin may be an antepartum indicator of fetal hypoxemia.


Assuntos
Líquido Amniótico/análise , Eritropoetina/análise , Sangue Fetal/análise , Complicações na Gravidez/metabolismo , Gravidez/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Gravidez em Diabéticas/metabolismo
12.
Obstet Gynecol ; 82(3): 353-8, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8355933

RESUMO

OBJECTIVE: To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS: Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 +/- 5.0 weeks, mean +/- standard deviation) and from 13 control fetuses (23.1 +/- 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS: Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid-gestation controls (6.1 +/- 3.9 versus 10.7 +/- 1.5 g/dL and 105.5 +/- 168.1 versus 12.5 +/- 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r = -0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25 = 12.3, multiple r2 = 0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeks' gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 +/- 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 +/- 3.5 g/dL) delivered by elective cesarean without labor (1246 +/- 856 versus 106 +/- 66 mU/mL, respectively, P < .05). CONCLUSION: Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeks' gestation.


Assuntos
Anemia Hemolítica Autoimune/sangue , Eritropoetina/sangue , Doenças Fetais/sangue , Hemoglobinas/análise , Hidropisia Fetal/sangue , Isoimunização Rh/sangue , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/terapia , Transfusão de Sangue Intrauterina , Sangue Fetal , Doenças Fetais/terapia , Idade Gestacional , Humanos , Hidropisia Fetal/complicações , Hidropisia Fetal/terapia , Análise de Regressão , Isoimunização Rh/complicações , Isoimunização Rh/terapia
13.
J Appl Physiol (1985) ; 72(6): 2354-63, 1992 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1629091

RESUMO

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.


Assuntos
Hematopoese/fisiologia , Hipóxia/fisiopatologia , Respiração/fisiologia , Doença da Altitude/sangue , Doença da Altitude/etiologia , Doença da Altitude/fisiopatologia , Animais , Modelos Animais de Doenças , Eritropoetina/biossíntese , Hipóxia/sangue , Rim/metabolismo , Masculino , Oxigênio/sangue , Ratos , Ratos Endogâmicos , Especificidade da Espécie
14.
Kidney Int Suppl ; 34: S46-8, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1762334

RESUMO

The severity of anemia in patients at different stages of the evolution of two tubulointerstitial nephropathies, Balkan endemic nephropathy and chronic pyelonephritis, was compared to clarify the previous observations that anemia appears earlier and is more severe in Balkan endemic nephropathy than in other renal diseases. The role of erythropoietin insufficiency as the cause of anemia in endemic nephropathy was studied as well. The severity of anemia increased with the impairment of renal function in endemic nephropathy and was similar to anemia in chronic pyelonephritis. However, in patients with endemic nephropathy at the initial stage of renal insufficiency significantly lower red cell concentrations were found compared with control subjects from the endemic region. In contrast, patients with pyelonephritis did not have decreased red cell concentrations at the early phase of their renal failure, suggesting that earlier appearance of anemia is characteristic for endemic nephropathy. To confirm this finding a study involving larger number of patients would be necessary. The serum erythropoietin levels, inappropriately low for the degree of anemia in patients with renal failure, were unrelated to the type of tubulointerstitial nephropathy.


Assuntos
Anemia/complicações , Nefropatia dos Bálcãs/complicações , Adulto , Idoso , Anemia/sangue , Nefropatia dos Bálcãs/sangue , Contagem de Eritrócitos , Eritropoetina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pielonefrite/sangue , Pielonefrite/complicações
15.
Biomed Pharmacother ; 46(1): 37-43, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1421034

RESUMO

In anemic patients on regular hemodialysis (HD), correction of anemia with recombinant human erythropoietin (rHuEpo) administered intravenously (iv) or subcutaneously (sc) was followed over a 2-month period. Monitoring serum Epo post-dose concentrations after the first iv rHuEpo injection and following another regular injection after 2 months of therapy with rHuEpo iv in 9 patients showed that the Epo elimination half-life was reduced from 7.48 h to 4.68 h. In the same patients the initially low percentage of erythroblasts and mature erythroid progenitors increased during 2 months of rHuEpo therapy. Because Epo molecules bound to Epo receptors are internalized in target cells we suggest that the expansion of the Epo responsive cell pool could explain the shorted Epo elimination time after 2 months of rHuEpo treatment. By monitoring serum Epo concentration following sc rHuEpo injection in 7 HD patients it was found that the modest increase in serum Epo levels (30-60 mU/ml) was sufficient to correct anemia.


Assuntos
Eritropoetina/sangue , Diálise Renal , Adulto , Anemia/tratamento farmacológico , Feminino , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
16.
Indian J Med Res ; 104: 304-10, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8979523

RESUMO

In order to better understand the mechanisms affecting erythropoietin (Epo) synthesis and red cell mass increase under chronic hypoxia, we examined Epo production and erythroid progenitors (CFU-E) in rats exposed to normobaric hypoxia for four weeks. Hypoxia induced the rise of hematocrit (Htc), hemoglobin (Hb) concentration and the red blood cell (RBC) number with a plateau in hematocrit values after two weeks. After 24 h of hypoxia, Epo levels were increased 20 fold, followed by a significant decrease. After the first week of hypoxia, the values were still higher than in the controls, but after two weeks Epo levels did not differ significantly from the normal values. The fall of Epo levels coincided with the plateau values of hematocrit. The changes in the CFU-E number followed the changes in Epo concentration: a two fold increase after 24 h of hypoxia; a further increase during the next two weeks reaching a peak on day 14, and then a progressive decrease at the time when Epo concentration was at a normal level. Although decreased, but still higher than normal, the CFU-E number during the last two weeks of hypoxia could be necessary for the maintenance of an achieved steady state under persistent hypoxic conditions with normal Epo concentration sufficient to maintain the existing rate of erythropoiesis.


Assuntos
Hipóxia Celular/fisiologia , Células Precursoras Eritroides/metabolismo , Eritropoetina/biossíntese , Animais , Doença Crônica , Feminino , Ratos , Ratos Wistar
17.
Eur J Med Res ; 2(9): 407-12, 1997 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-9300939

RESUMO

In this study factors possibly contributing to the development of erythrocytosis after renal transplantation (PTE) were analyzed. Out of 131 transplanted patients nine developed PTE (mean hemoglobin 17. 9 +/- 0.3 g/dl) 2 to 27 months after transplantation (group 1) and were compared to the nine with normal hemoglobin concentration (mean hemoglobin 12.4 +/- 0.2 g/dl, control group 2). The study was performed about two years after transplantation (25 +/- 3.9 months group 1 and 23.7 +/- 2.6 months group 2). Immunosuppressive therapy given in standard doses consisted of cyclosporine, azathioprine and prednisone. At the onset of the study no difference in renal graft function was noted between the groups (for group 1 sCr = 111.7 +/- 10.4 micromol/l and for group 2 sCr = 154.6 +/- 27.6 micromol/l). The mean serum immunoreactive erythropoietin (Epo) levels were significantly higher in PTE patients compared to control group of patients (33.9 +/- 4.6 mU/ml vs 21.6 +/- 2.5 mU/ml, p = 0.03). In addition, the ratio between observed to expected (O/E) Epo, a useful index in assessing Epo secretion in renal transplant patients, was ten times higher for group 1 than for group 2 (Median value 10.0 vs. 1.05). Spontaneous growth of Burst-forming unit- erythroid (BFU-E) in peripheral blood was detected in 5 out of 9 patients from group 1 and none in patients from group 2 (p = 0.04). Burst Promoting Activity (BPA) in Phytohemagglutinine Stimulated Leukocytes Condition Medium (PHA-LCM) from patients blood were higher in the PTE patients than in controls. Whole blood cyclosporine levels were higher in group 1 than in group 2 throughout the first 30 weeks after transplantation. It was concluded that sustained erythropoiesis after correction of renal anemia by kidney transplantation, leading to PTE could be explained as a consequence of increased levels of Epo and BPA and increased sensitivity of early erythroid progenitors to these stimulators induced by high cyclosporine levels.


Assuntos
Transplante de Rim/efeitos adversos , Policitemia/etiologia , Adulto , Ensaio de Unidades Formadoras de Colônias , Meios de Cultivo Condicionados , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Eritropoese , Eritropoetina/sangue , Feminino , Células-Tronco Hematopoéticas/patologia , Humanos , Técnicas In Vitro , Transplante de Rim/fisiologia , Masculino , Policitemia/sangue , Fatores de Risco
18.
Adv Exp Med Biol ; 271: 9-15, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2486292

RESUMO

Serum erythropoietin (Ep) was measured by radioimmunoassay before and 24 hours after therapeutic phlebotomies in patients with polycythemia vera (PV) and in normal subjects before and after phlebotomies of comparable volumes. In addition the in vivo oxygen affinity of hemoglobin (P50) was calculated, and red cell indices and 2,3 DPG values were measured. Paired t tests determined whether the differences between pre- and post--phlebotomy values were statistically significant. Blood hemoglobin (Hb) levels declined after phlebotomy, and generally continued to be at or above normal levels. Serum Ep increased after phlebotomy in both groups of subjects. The in vivo P50 value for patients with PV (29.4 +/- 0.4 mmHg) was significantly (p less than 0.005) greater than the normal value (27.2 +/- 0.5). Seven of the PV patients (5 males, 2 females) were restudied. Their Hb and hematocrit values were either normal or slightly higher than normal. The MCV for 4 males and 1 female was below normal. The MCHC was slightly lower than normal and reticulocytosis was not present. The male PV patients had greater than normal 2,3 DPG values and most had right-shifted P50 values. There was no correlation between 2,3 DPG values and P50 values. The female patients did not have 2,3 DPG values consistently greater than normal and their P50 values were not right shifted. These results showed that serum EP increased in response to small reductions in Hb even when subnormal Hb values were not produced. The reduced affinity of Hb in PV patients may explain earlier observations that patients with PV have lower levels of urinary or plasma Ep than normals with the same hematocrits.


Assuntos
Sangria , Eritropoetina/sangue , Hemoglobinas/metabolismo , Oxigênio/metabolismo , Policitemia Vera/sangue , 2,3-Difosfoglicerato , Adulto , Ácidos Difosfoglicéricos/sangue , Índices de Eritrócitos , Eritropoetina/metabolismo , Feminino , Humanos , Masculino , Policitemia Vera/terapia
19.
Am J Vet Res ; 47(10): 2274-7, 1986 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3022625

RESUMO

Erythropoiesis was evaluated in 5 cats at base line with normal PCV and then in the same cats with anemia induced by phlebotomy and in 5 other cats with nonregenerative anemia from community-acquired feline leukemia virus (FeLV) infection. The hematologic evaluation included complete blood cell and reticulocyte counts, marrow morphologic features, determination of serum erythropoietin concentrations by radioimmunoassay, ferrokinetic studies, and in vitro marrow culture of early erythroid progenitors (erythroid burst-forming units; BFU-E) and late erythroid progenitors (erythroid colony-forming units; CFU-E). Phlebotomized cats developed marrow erythroid hyperplasia and an increased reticulocyte count. Ferrokinetic studies revealed an increase in plasma iron turnover from 1.4 to 3.8 mg of Fe/dl of blood/day and RBC use from 50.4% to 78.5%. The mean CFU-E number and CFU-E/BFU-E ratio increased after phlebotomy, but the increase was not significant (P greater than 0.05). Serum erythropoietin values did increase significantly. In FeLV-infected cats, a nonregenerative anemia was demonstrated by marrow erythroid hypoplasia and a low total reticulocyte count. An increased percentage of rubriblasts and prorubricytes was observed in 4 of the 5 cats. Although serum erythropoietin values were high (321 +/- 123 mU/ml vs normal 14 +/- 1 mU/ml), ferrokinetic data revealed decreased erythropoiesis. Marrow culture studies in the FeLV-infected cats also revealed low numbers of BFU-E and CFU-E, but normal numbers of granulocyte-macrophage progenitors remained. Seemingly, the FeLV infection impaired the ability of feline marrow to respond physiologically to anemia.


Assuntos
Anemia/veterinária , Doenças do Gato/sangue , Gatos/sangue , Eritropoese , Leucemia/veterinária , Anemia/sangue , Animais , Biópsia por Agulha/veterinária , Medula Óssea/patologia , Eritropoetina/sangue , Feminino , Ferro/metabolismo , Cinética , Leucemia/sangue , Vírus da Leucemia Felina , Masculino , Valores de Referência , Análise de Regressão
20.
Health Phys ; 63(4): 427-42, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1526784

RESUMO

The laboratory mouse is a primary animal model for experimental radiation biology and pharmacology. The usefulness of the mouse for those purposes is enhanced if detailed data are available to define a Reference Mouse [weight and composition of soft tissues and bones and their in-life content of plasma and extracellular water (ECW)]. Only fragmentary data are available for wet weights and plasma volumes of soft tissues and bones of mice; there are no reports of total volume or distribution of ECW in mouse tissues. To remedy those defects, wet weight and composition of all major organs and soft tissues were measured, and measurements were made or estimates obtained for wet weights and composition of all bones of the young adult (12 to 13 wk old) female Swiss-Webster mouse. 125I-transferrin was used as a tracer for plasma, and 22Na was used as a tracer for ECW. Tissue weight and tracer measurements were conducted using the metabolic balance approach and a freezing technique that avoids blood loss during dissection. Results compare favorably with published weights and plasma volumes of tissues of mature mice of both genders and other strains. Total plasma volume (48.9 +/- 4.4 microL g-1) and Na-space (232 +/- 15 microL g-1), and the specific plasma and ECW volumes of vascular mouse tissues, exceed those of rat tissues. Applications of the data are presented: (1) interpretation of plutonium uptake kinetics in the mouse; (2) estimation of masses of mineralized bone tissue (1.92 g), bone marrow (1.2 g), and endosteal (BS) cells (0.2 g) of the mouse.


Assuntos
Apoproteínas/farmacocinética , Sangue/metabolismo , Água Corporal/metabolismo , Espaço Extracelular/metabolismo , Camundongos/metabolismo , Modelos Biológicos , Sódio/farmacocinética , Transferrina/farmacocinética , Animais , Medula Óssea/anatomia & histologia , Osso e Ossos/anatomia & histologia , Osso e Ossos/metabolismo , Feminino , Tamanho do Órgão , Ratos , Valores de Referência , Distribuição Tecidual
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