Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach

We investigated the in vitro erythroid progenitor growth and the effects of sera on normal-marrow CFU-E (colony-forming units - erythroid) growth in 2 patients with renal failure on regular hemodialysis following a prior history of polycythemia vera (PV). PV was diagnosed 3 and 11 years, respectively, before the development of terminal renal failure. One of the patients had entered a spent phase of PV as characterized by diffuse extensive myelofibrosis and anemia; the other also had mild myelofibrosis. The serum erythropoietin (EPO) levels were low or normal on serial measurements by radioimmunoassay. There was no correlation between the hematocrit values and serum EPO levels. EPO-independent erythroid colonies were present in the cultures of bone marrow and peripheral blood cells from both patients after renal failure in the anemic state. With the addition of various concentrations of EPO, the number of erythroid colonies increased as the concentrations of EPO increased which was in accordance with the clinical observation that 1 patient with postpolycythemic myeloid metaplasia partially responded to recombinant human EPO therapy. In the EPO-dependent CFU-E assay, normal-marrow CFU-E numbers supported by 10% of the patient sera were less than those by normal sera. In the absence of EPO in cultures, no erythropoietic activity was found in the patients' sera. Our study on uremic patients with underlying PV showed that the biologic characteristics of autonomous erythroid progenitor growth for PV persisted during the spent phase and after the development of terminal renal failure with anemia. The erythroid progenitors responded to EPO both in vitro and in vivo. Their sera exhibited an inhibiting effect on the growth of normal-marrow erythroid progenitors.     

Sex differences in the relation of visceral adipose tissue accumulation to total body fatness

With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = -0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Re-accreditation, re-certification and the postgraduate database

Anemia associated with ACE inhibitors is rare but it may cause problems especially in patients with renal disease. This study assessed the acute effect of trandolapril, an ACE inhibitor, on serum erythropoietin (EPO) levels in uremic and hypertensive patients. Trandolapril 2 mg/day was given orally for three days and blood samples were collected on the first and third day. Trandolapril led to a significant decrease in serum EPO in patients with chronic renal failure. Although the drug lowered serum EPO in hypertensive patients, this effect was not statistically significant. This drop in serum EPO levels may be one of the mechanisms by which ACE inhibitors cause anemia, or worsen anemia, in uremic patients and further studies are needed to clarify this point.     

Hydrogen peroxide induces protection against lethal effects of cumene hydroperoxide in Escherichia coli cells: an Ahp dependent and OxyR independent system?

Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 +/- 0.8 g/dl at baseline to 10.7 +/- 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 +/- 7.5 to 23.6 +/- 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.     

Recombinant human erythropoietin resistance in hemodialysis. Effects of paired filtration dialysis

A percentage of hemodialysis (HD) patients are resistant to recombinant human erythropoietin (rHuEPO), a phenomenon that occurs less frequently in patients dialyzed with biocompatible membranes (M) and in peritoneal dialysis. The authors evaluated the effects of paired filtration dialysis (PFD)--a dialysis technique based on the use of an emophan M in conjunction with a polysulphone M--on erythropoiesis in HD patients resistant to rHuEPO. Twelve HD patients with anemia resistant to long-term therapy with rHuEPO (200.24 U/kg body weight three times per week intravenously for 10.2 months) were studied. Patients had been treated for an average of 46.9 months with bicarbonate HD, using cuprophan M (Phase A) and, successively, for 12 months by PFD (Phase B). The following parameters were evaluated monthly: 1) hemoglobin and hematocrit values; 2) serum levels of erythropoietin (EPO); and 3) serum levels of interleukin (IL)-3, IL-6, IL-10, IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). At the end of Phase A and Phase B, patients underwent bone marrow biopsies to evaluate 1) bone marrow burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) proliferative capacity, and 2) bone marrow mononuclear cell EPO-receptor (EPO-R) number. During Phase B, there was a progressive rise in hematocrit and hemoglobin values, so that within the sixth month, the rHuEPO dose was reduced to 80 +/- 15 U/kg body weight three times per week. At the same time, an increase in serum IL-3, IL-6, and IL-10 levels was seen, whereas serum IL-1 beta, TNF-alpha, and IFN-gamma levels decreased. This was accompanied by a rise in BFU-E and CFU-E growth and in bone marrow mononuclear cell EPO-R number. During Phase B, after the dialysis session, serum EPO levels increased by about 30% in comparison with pre dialysis values, whereas during Phase A they decreased by about 14%. In HD patients, EPO resistance may caused either by absorption of rHuEPO to the cuprophan M, or an increased release of cytokines that inhibit erythropoiesis, such as IL-1 beta, TNF-alpha, and IFN-gamma, and to a decrease in stimulatory cytokines such as IL-3, IL-6, and IL-10. These negative phenomena are reversed by the use of biocompatible dialysis techniques such as PFD.     

Autoantibodies to human recombinant erythropoietin in patients with systemic lupus erythematosus: correlation with anemia

OBJECTIVE: To investigate the existence of circulating autoantibodies to erythropoietin (EPO) in sera from patients with systemic lupus erythematosus (SLE), and to correlate their presence with anemia and clinical activity. METHODS: Ninety-two consecutive patients with SLE, 80 patients with rheumatoid arthritis, and 42 normal individuals were studied. The patients with SLE were categorized into 3 groups according to hemoglobin (Hgb) level: group A (45 patients with Hgb > 12 gm/dl), group B (26 patients with Hgb 10.1-12 gm/dl), and group C (21 patients with Hgb < or = 10 gm/dl). In all patients with SLE, the disease activity was evaluated using the European Consensus Lupus Activity Measurement scale. Antibodies to EPO were detected using an enzyme-linked immunosorbent assay and purified recombinant human EPO as antigen. The specificity of the method was evaluated with homologous and cross-reactive inhibition assays. RESULTS: Antibodies to EPO were found in 15.2% of the SLE patient sera. The distribution of these antibodies among the 3 groups of SLE patients was as follows: 8.8% (4 of 45) from group A, 15.4% (4 of 26) from group B, and 28.6% (6 of 21) from group C. The prevalence of antibodies to EPO in patients with severe anemia (group C) was statistically significantly higher compared with patients without anemia (chi(2) = 4.31, P < 0.05). Patients with antibodies to EPO had higher disease activity scores (P < 0.005) and lower levels of the C4 component of complement (P < 0.05) compared with patients without antibodies to EPO. CONCLUSION: In this study, the presence of antibodies to EPO in the sera of SLE patients is demonstrated for the first time. The presence of these antibodies is associated with severe anemia and active disease.     

Endogenous erythropoietin in patients on regular dialysis therapy

In a group of 66 patients with chronic renal failure having regular dialyzation treatment the serum concentration of endogenous erythropoietin (EPO), haemoglobin levels (Hb), haematocrit (Ht) and serum creatinine (Cr) were assessed. The examined subjects were never treated with recombinant erythropoietin and deficiency of iron, folic acid and vitamin B12 was ruled out. Endogenous EPO was assessed by the authors own RIA method, normal values being 24-42 mU/ml. The mean EPO concentration in the whole group of patients was 37.4 +/- 15.3 mU/ml, whereby 12 patients had an EPO serum concentration higher than the upper range of normal values. Between EPO concentrations and Hb values a certain positive correlation was found (r = 0.42). A similar relationship was revealed also between EPO concentrations and Ht values (r = 0.41). Patients with EPO values higher than 42 mU/ml had, as compared with the other patients, significantly higher values of erythrocytes (p .001). Statistical analysis did not reveal any relationship between EPO and Cr concentrations (r = -0.04). A low negative correlation was found between Cr and Hb values (r = -0.31) and between Cr and Ht values (r = -0.25). In the discussion the authors analyze the contemporary state of the problem of anaemia in chronic renal failure. Based on hitherto assembled knowledge they formulated the hypothesis ascribing considerable pathogenetic importance in the development of anemia to reduced sensitivity of bone marrow to EPO, probably as a result of retention of uraemic toxins and inhibitors of erythropoiesis. Inadequate EPO formation could be only a factor which makes it impossible for the developing anaemia to compensate and is due to an animpaired feedback at the level of recognition of the hypoxic signal.     

Pathology of preinvasive and excellent prognosis breast cancer

BACKGROUND: Erythropoietin (EPO) therapy is a common and effective treatment for the correction of anemia in patients with end-stage renal disease. Simultaneous treatment with angiotensin-converting enzyme (ACE) inhibitors for the control of hypertension and/or heart failure is often necessary. Recent reports in the literature have raised concern about a potential interaction between these drugs, with a resultant decreased EPO efficacy. METHODS: To investigate whether this interaction occurs in chronic dialysis patients, we retrospectively reviewed the records of 175 patients receiving chronic dialysis. All study patients were treated with EPO for at least 3 months, and had normal iron indices. Patients were treated with ACE inhibitors for at least 3 months, at a constant daily dose for at least 1 month (group 1, n = 32), or did not receive ACE inhibitors (group 2, n = 143). Patients with infections or overt iron deficiency were excluded. Total weekly EPO doses and hematocrit (Hct)/hemoglobin (Hgb) values in the two groups were compared. Variables known to affect response to EPO were compared, including ferritin, transferrin saturation, dialysis dose and serum aluminum. RESULTS: Total weekly EPO dose was 17,358 +/- 6,871 units in group 1 and 17,612 +/- 7,744 units in group 2 (p = 0.854). The achieved Hct was 32.1 +/- 4.4% (group 1) and 30.5 +/- 4.0% (group 2) (p = 0.079). Similarly, Hgb, ferritin, transferrin saturation, Kt/V, and serum aluminum were not different. The dose or duration of ACE inhibitor therapy did not affect Hgb or Hct. Thus, ACE inhibitor therapy does not appear to affect response to EPO in chronic dialysis patients.     

Erythropoietin in hepatocellular carcinoma

Hemopoietic alterations may occur during tumoral diseases, determining anemia. In most cases, serum EPO levels were lower than normal values. Hepatocellular carcinoma (HCC), one of the most frequent malignancies world-wide, is often characterized by mild anemia and increased serum EPO levels. We studied 30 HCC patients and 20 healthy subjects. We found that HCC patients presented higher serum EPO levels than healthy controls. In HCC patients, there was a significant inverse correlation between serum EPO levels and red blood cell count or hemoglobin levels. We postulated that the elevated serum EPO levels observed in these patients may be due to reduced hepatic clearance of EPO, and to the influence of cytokine-mediated inflammatory factors.     

Anemia in children with cancer is associated with decreased erythropoietic activity and not with inadequate erythropoietin production

A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To further elucidate the pathophysiology of anemia in children with cancer, we measured serum soluble transferrin receptor (sTfR), a quantitative marker of erythropoiesis, and serum EPO at time of diagnosis and during chemotherapy in children suffering from solid tumor or leukemia. We determined serum EPO in 111 children (55 leukemia, 56 solid tumors) at time of diagnosis. In the last 44 patients (23 leukemia and 21 solid tumors), sTfR levels were also measured. Serum EPO together with sTfR levels were also determined in 60 children receiving chemotherapy (29 leukemia, 31 solid tumors). These results were compared with those obtained from appropriate control groups. In all patients, we found a highly significant correlation between the logarithm of EPO (log[EPO]) and the hemoglobin (Hb) level. In all subsets of patients, sTfR levels were inappropriately low for the degree of anemia. Neither leukemic nor solid tumor groups showed a significant inverse relationship between log(sTfR) and the Hb level as would be expected in anemic patients with appropriate marrow response. Thus, in children with cancer, anemia is associated with a decreased total bone marrow erythropoietic activity which, in contrast to what has been reported in anemic cancer adults, is not related to defective EPO production.     

Effect of chronic renal failure on the expression of erythropoietin message in a murine model

The anemia of chronic renal failure (CRF) is largely due to decreased production of erythropoietin (EPO) by the kidney. A small amount of EPO also originates from extra-renal sources, and this would be expected to assume a more important role in maintaining erythropoiesis when renal production is impaired. In this study, we examined the production of EPO mRNA by RT-PCR in kidney, liver, and bone marrow tissues isolated from normal mice, mice rendered acutely anemic by phlebotomy, and from mice with surgically induced CRF. The induction of acute anemia results in an expected increase in the expression of EPO mRNA in renal and hepatic tissue. In contrast, while the expression of EPO mRNA was expectedly reduced in the kidney from CRF mice, it was completely absent in the liver of these same animals. EPO mRNA expression was also absent in the bone marrow in both states of acute anemia and CRF. These results show that CRF can directly or indirectly can suppress the extrarenal production of EPO by the liver and that this effect may further aggravate the anemia of CRF.     

In-vitro growth patterns of bone marrow erythroid progenitors from patients with post-renal transplant erythrocytosis

BACKGROUND: Erythrocytosis is relatively common after renal transplantation and is associated with a higher risk of thromboembolism. Its aetiology is unclear and there is still debate about the most frequently suggested causes. The culture in vitro of erythroid progenitors is regarded as a useful tool for the differential diagnosis of patients with unclear erythrocytosis. We studied the growth in vitro of bone marrow erythroid progenitors from renal transplant patients with erythrocytosis and controls without erythrocytosis. SUBJECTS AND METHODS: Thirteen renal transplant patients with erythrocytosis and 12 normocythaemic renal transplant controls were studied. The clinical characteristics of these patients were evaluated and serum erythropoietin (Epo) and ferritin levels were determined. Bone marrow erythroid progenitors were cultured both with and without the addition of Epo to the medium. RESULTS: Samples from six polycythaemic patients and seven controls did not grow spontaneously in the absence of exogenous Epo. Three cases of post-transplant erythrocytosis and five controls produced CFU-E, but not BFU-E. A few CFU-E and BFU-E grew spontaneously in samples from four polycythaemic patients but not in samples from the controls. Addition of 1 unit per millilitre Epo caused similar increases in the number of colonies in both polycythaemic patients and controls. Of the nine patients eligible for follow-up, all four with spontaneous growth of BFU-E had transient erythrocytosis and four of the five patients with no spontaneous growth or spontaneous growth of CFU-E only had persistent erythrocytosis requiring treatment with ACE inhibitors. CONCLUSIONS: Pathophysiology of post-transplant erythrocytosis is heterogeneous. In one-third of the patients, there was unexpected, spontaneous and transient growth of BFU-E which was not predictive of permanent erythrocytosis. The results of stem-cell studies suggest that in these cases erythrocytosis may be caused by defective regulation of erythroid progenitor proliferation, possibly due to particular cellular interactions or the effect of cyclosporin on erythropoiesis.     

The effect of subcutaneous r-HuEPO in cancer patients receiving chemotherapy with anemia: a preliminary report

BACKGROUND: Chemotherapy-related anemia in cancer patients is often encountered in clinical practice. It can reduce patient's compliance and tolerance to continuing chemotherapy. The mechanism of anemia may be ascribed to either decreasing serum EPO concentration or reducing sensitivity of EPO. Exogenous supply of EPO has shown to be effective in control of cancer-related anemia in early reports. This study preliminarily explored the efficacy and safety of r-HuEPO for cancer patients with anemia during the cytotoxic chemotherapy period in Taiwan. METHODS: Sixteen cancer patients receiving cyclic chemotherapy with anemia (Hgb < or = 10.5 g/dl) and without other systemic organ dysfunction, cerebral metastasis, uncontrolled hypertension, or presence of anemia attributable to causes other than cancer and chemotherapy entered the study. All patients received r-HuEPO 150 u/kg subcutaneous injection tiw for a total of 16 weeks. The efficacy determinations was based on the effect of r-HuEPO on hematological parameters, transfusion requirements, quality of life assessment, and physician's global assessment. Safety was assessed based on clinical laboratory tests, vital sign measurements and the incidence and severity of adverse experiences. RESULTS: There were no changes of WBC and platelet count in 4, 8, 12 and 16 weeks of r-HuEPO therapy. The mean hemoglobin values at baseline, week 4, 8, 12, and 16 were 9.2 +/- 1.0 g/dl, 11.4 +/- 0.9 g/dl, 11.6 +/- 1.8 g/dl, 11.8 +/- 1.8 g/dl, and 12.2 +/- 2.3 g/dl, respectively (p < 0.001). The mean hematocrit values at baseline, week 4, 8, 12, and 16 were 28.3 +/- 3.4%, 36.0 +/- 2.8%, 36.3 +/- 5.7%, 37.8 +/- 6.0%, and 40.1 +/- 7.1%, respectively (p < 0.0005). The use of r-HuEPO had the marginal effect on the increase of patient's energy and activity. No adverse impacts on patient's vital signs were noted except 2 incidences of systolic hypertension and one episode of diastolic hypertension in the week 4. CONCLUSIONS: Subcutaneous injection of r-HuEPO at the dose of 150 u/kg tiw was safe and effective in increasing patient's hematocrit and RBC mass, and decreasing their blood transfusion requirement. Whether the current dosage of 150 u/kg tiw is the optimal treatment for chemotherapy-related anemia still needs further study.     

Cause analysis of pain following vitreous surgery and nursing strategies]

OBJECTIVE: To assess the efficacy of "method of activating blood circulation and removing stasis (ABCRS)" in treating polycythemia vera. METHODS: 28 cases of polycythemia vera were treated with ABCRS and observed with bone marrow colonies. RESULTS: 15 casses were responsibe, of them 4 cases reached clinical remission, 11 cases were improved. Both bone marrow colonies of colony forming unit-erythroid dependent of erythropoietin (EPO + CFU-E) and colonies of CFU-E independent of EPO. (EPO-CFU-E) from these cases decreased significantly, especially the latter. ABCRS mainly suppressed the proliferation and differentiation of EPO-CFU-E. In addition, bone marrow colonies of colony formng unit-fibroblastoids (CFU-F) from these cases also changed obviously. CONCLUSION: ABCRS is effective in treating polycythemia vera.     

Modulation of erythropoietin production by selective adenosine agonists and antagonists in normal and anemic rats

Hypoxia or anemia is the fundamental stimulus for erythropoietin (EPO) production. Recent in vitro studies suggest that EPO secretion in response to hypoxia is regulated by adenosine in the kidney. In order to examine the in vivo effect of adenosine on EPO production, we determined the effects of adenosine receptor agonists and antagonists on serum EPO concentration in normal and anemic rats. In normal rats, intravenous injection of adenosine agonists (NECA, CHA and CGS-21680) dose-dependently stimulated EPO production. Pretreatment with KW-3902, an adenosine A1 antagonist with modest A2b antagonistic action, or KF17837, an adenosine A2a antagonist, inhibited the NECA (0.1 mg/kg, i.v.)-stimulated EPO production. Anemic hypoxia, induced by 2% (v/w body weight) blood withdrawal, increased serum EPO concentration from 38 +/- 2 to 352 +/- 76 mU/ml, with the increased serum adenosine concentration in the renal vein. KF17837 (0.1 mg/kg, i.v.), but not KW-3902 (0.1 mg/kg, i.v.), inhibited the anemic hypoxia-induced increase in EPO production. The present findings support the notion that adenosine mediates the EPO production in response to hypoxia in the kidney.     

Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival

PURPOSE: We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival. MATERIALS AND METHODS: Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes. RESULTS: IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2. CONCLUSIONS: IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.     

Erythropoiesis in chronic renal disease

The diminished erythropoiesis in the anemia of chronic renal disease has been attributed to three possible factors: (1) decreased erythropoietin production, (2) inhibition of erythropoietin activity, and (3) decreased bone marrow response to erythropoietin. In this report we isolated and evaluated these parameters in 19 patients with chronic renal disease, nine patients with iron-deficiency anemia, and seven control subjects. The results in patients with chronic renal failure were as follows: (1) erythropoietin enhanced heme synthesis in bone marrow cell cultures by 88 +/- 12 per cent in renal failure, as compared to 65 +/- 7 per cent in the control group; (2) plasma erythropoietin activity did not increase appropriately for the degree of anemia; and (3) erythropoietin inhibitor activity in renal failure was not greater than in a control group. In conclusion, the relative failure of erythropoiesis in chronic renal disease appears to be due primarily to decreased production of erythropoietin and not to diminished marrow response to erythropoietin.     

Oral aluminum administration to rats wih normal renal function. 1. Impairment of erythropoiesis

Aluminum (Al) toxicity has been mainly investigated in uremic patients although healthy subjects and patients without renal insufficiency are not exempt from its potential deleterious effects. This experimental study aims to elucidate the action of different doses of Al citrate on in vivo erythropoiesis and find out whether the metal exerts a local toxic effect upon the bone marrow late erythroid progenitor cells. The groups in the first experimental series were: C1 (n=5) controls and TAl-1 (n=5) rats receiving 1 micromol Al citrate/g body weight/day by gavage. Colony-forming units-erythroid (CFU-E) development was inhibited in the TAl-1 group, but the median osmotic fragility (MOF) and hematocrit (Ht) values were similar to those of the C1 group. The groups in the second series were C2 (n=5) controls and TAl-2 (n=5) rats receiving Al citrate in drinking water (100 mmol/l). The TAl-2 group showed decreased Ht, hemoglobin concentration, MOF and red blood-cell life-span values (P<0.05), and a marked inhibition of the CFU-E development (P<0.01). Serum and bone Al concentrations were increased in both Al-treated groups (P < 0.01). There was a dose-dependent increase in bone Al levels (P < 0.01) and a dose-dependent decrease of CFU-E development (P<0.05). The CFU-E development was inversely correlated with the bone Al content (r=-0.79; P<0.05). The results demonstrate that even very low doses of Al citrate impair erythropoiesis in vivo and higher doses exert a deleterious action on both CFU-E and mature erythrocytes. This might show a local effect of Al on CFU-E caused by the bone sensitivity to the metal accumulation.     

Effects of the Breathe Right nasal strips on nasal ventilation

Erythropoietin (EPO) is the hematopoietic growth factor that regulates red cell production. There is a direct relationship between its secretion and tissue hypoxia. Above sea level, oxygen concentration diminishes. This causes an increase of hemoglobin and hematocrit; this effect could be the consequence of higher EPO levels. Currently, evaluation of baseline serum EPO levels is very important in the differential diagnosis of anemia and erythrocytosis. The purpose of the present work was to report the EPO levels on a group of healthy blood donors living in Mexico City, 2,240 m above sea level. Two-hundred twenty blood donors were selected to measure serum EPO; there were 168 males and 52 females. Median EPO levels of the entire population were 7.5 mU/mL (percentile interval, PI, 1-18). Median EPO levels were 7.6 (PI 1-18) and 7.5 (PI 1-16.9) for men and women, respectively. We did not find differences in serum EPO levels among previous reports in other populations and the values determined in this study.     

Adenine dinucleotide-mediated activation of glycogen phosphorylase in isolated liver cells

PTH is incriminated as an uraemic toxin involved in the pathogenesis of anaemia in chronic renal failure. This fact was the background of our present studies performed in 14 patients with noninflammatory acute renal failure (NARF). Plasma levels of erythropoietin (EPO) and parathyroid hormone (PTH) were estimated in the anuric/oliguric (a/o) and polyuric (p) phase of NARF. In the a/o phase plasma EPO levels were predominantly normal, although inappropriately low to the degree of anaemia. In 50% of patients with NARF episodic short-term increases of plasma EPO levels were noticed which were not caused by worsening of anaemia. In the p phase plasma EPO concentrations were in the normal range (17.9 +/- 3.3 mU/ml) in spite of the same degree of anaemia as in the a/o phase. Plasma PTH levels were significantly elevated during the a/o phase (1.14 +/- 0.1 ng/ml), with a tendency to decline in the p phase (0.87 +/- 0.2 ng/ml). No correlation was found between plasma EPO and PTH concentrations. Results presented in this study suggest presence of relative EPO deficiency both during the a/o and p phases of NARF. As plasma PTH levels were not significantly correlated with serum EPO concentrations, its role in the pathogenesis of suppressed EPO levels seems unproven. Results presented in this study suggest deterioration of the physiological feedback between EPO secretion and the magnitude of erythropoiesis in NARF.