Proteção renal com eritropoetina em modelo de isquemia renal no rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Associação entre doença renal e anemia em idosos atendidos em um centro se atenção integrada a melhor idade de Manaus (AM)

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Carbohydrate and glutamine supplementation modulates the Th1/Th2 balance after exercise performed at a simulated altitude of 4500 m

Objective: The aim of this study was to evaluate the effect of carbohydrate or glutamine supplementation, or a combination of the two, on the immune system and inflammatory parameters after exercise in simulated hypoxic conditions at 4500 m.Methods: Nine men underwent three sessions of exercise at 70% VO2(peak) until exhaustion as follows: 1) hypoxia with a placebo; 2) hypoxia with 8% maltodextrin (200 mL/20 min) during exercise and for 2 h after; and 3) hypoxia after 6 d of glutamine supplementation (20 g/d) and supplementation with 8% maltodextrin (200 mL/20 min) during exercise and for 2 h after. All procedures were randomized and double blind. Blood was collected at rest, immediately before exercise, after the completion of exercise, and 2 h after recovery. Glutamine, cortisol, cytokines, glucose, heat shock protein-70, and erythropoietin were measured in serum, and the cytokine production from lymphocytes was measured.Results: Erythropoietin and interleukin (IL)-6 increased after exercise in the hypoxia group compared with baseline. IL-6 was higher in the hypoxia group than pre-exercise after exercise and after 2 h recovery. Cortisol did not change, whereas glucose was elevated post-exercise in the three groups compared with baseline and pre-exercise. Glutamine increased in the hypoxia + carbohydrate + glutamine group after exercise compared with baseline. Heat shock protein-70 increased post-exercise compared with baseline and pre-exercise and after recovery compared with pre-exercise, in the hypoxia carbohydrate group. No difference was observed in IL-2 and IL-6 production from lymphocytes. IL-4 was reduced in the supplemented groups.Conclusion: Carbohydrate or glutamine supplementation shifts the T helper (Th)1/Th2 balance toward Th1 responses after exercise at a simulated altitude of 4500 m. The nutritional strategies increased in IL-6, suggesting an important anti-inflammatory effect. (C) 2014 Elsevier Inc. All rights reserved.

Consultas de enfermagem com pacientes em tratamento para hepatite C

Infection with hepatitis C virus (HCV) is a worldwide problem of public health and who estimates 2.5% to 4.9% of infection by this virus among the population. This means that there are 3.9 to 7.6 million people at risk of developing cirrhosis or liver cancer. In Brazil, 20% to 58% of patients with chronic liver disease have antibodies to HCV (anti-HCV). To characterize the profile of patients undergoing treatment for hepatitis C in the Ambulatory General HC-FMB/UNESP, identify aspects of the disease and the phases of nursing process addressed during consultation. Transverse and descriptive study involving 38 patients undergoing treatment for Hepatitis C in Ambulatory General Area (Viral Hepatitis) in the period from July to September 2010. The population consisted of 38 patients, most of the males with completed higher education level, Catholic, married and aged predominantly between 41 and 60 years. Among the drugs used, we find the use of antihypertensive, antidepressant / anxiolytic and antidiabetic / hypoglycemic. With respect to specific medications used to treat hepatitis C, we found the use mainly of alfapeguinterferona 2b + ribavirin. The drugs used were complementary erythropoietin and filgastrim. There was a predominance of fibrosis 2 (F2) and genotype 1 (G1). Regarding the means of contamination, it was stressed blood transfusion and injection drug use. The most frequent drug reactions were decreased appetite, weight loss and discouragement. : The Nursing Process is considered a valuable tool in caring for patients with hepatitis C, because it works as identifying aspects of lifestyle, needs and potential of these patients and allows the deployment of humanized care strategies aimed at reduction of health hazards and improving the quality of life of these patients

Fatores indutores e supressores da eritropoiese em caninos doentes renais crônicos

Pós-graduação em Medicina Veterinária - FCAV

Efeitos da administração de eritropoietina na dislipidemia e na hipertrofia ventricular esquerda de camundongos hiperlipidêmicos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of Brazil Nut Supplementation on Plasma Levels of Selenium in Hemodialysis Patients: 12 Months of Follow-up

Background: Large amounts of reactive oxygen species are produced in hemodialysis (HD) patients, and, at higher concentrations, reactive oxygen species are thought to be involved in the pathogenesis of cardiovascular disease. It has been proposed that selenium (Se) may exert an antiatherogenic influence by reducing oxidative stress. The richest known food source of Se is the Brazil nut (Bertholletia excelsa, family Lecythidaceae), found in the Amazon region. Objective: The objective of this work was to determine if Se plasma levels in HD patients submitted to a program of supplementation during 3 months with 1 Brazil nut by day could be sustained after 12 months. Methods: A total of 21 HD patients (54.2 +/- 15.2 years old; average time on dialysis, 82.3 +/- 51.6 months; body mass index, 24.4 +/- 3.8 kg/m(2)) from the RenalCor Clinic in Rio de Janeiro, Brazil, were followed up 12 months after the supplementation study ended. The Se plasma levels were determined by atomic absorption spectrophotometry with hydride generation. Results: The Se Plasma levels (17.3 +/- 19.9 mg/L) were below the normal range (60 to 120 mu g/L) before nut supplementation, and after 3 months of supplementation, the levels increased to 106.8 +/- 50.3 mu g/L (P < .0001). Twelve months after supplementation, the plasma Se levels decreased to 31.9 +/- 14.8 mu g/L (P < .0001). Conclusions: The data showed that these patients were Se deficient and that the consumption of Brazil nut was effective to increase the Se parameters of nutritional status. Se levels 12 months after the supplementation period were not as low as presupplementation levels but yet significantly lower, and we needed to motivate patients to adopt different dietary intake patterns. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.

Does recombinant human Epo increase exercise capacity by means other than augmenting oxygen transport?

[EN] This study was performed to test the hypothesis that administration of recombinant human erythropoietin (rHuEpo) in humans increases maximal oxygen consumption by augmenting the maximal oxygen carrying capacity of blood. Systemic and leg oxygen delivery and oxygen uptake were studied during exercise in eight subjects before and after 13 wk of rHuEpo treatment and after isovolemic hemodilution to the same hemoglobin concentration observed before the start of rHuEpo administration. At peak exercise, leg oxygen delivery was increased from 1,777.0+/-102.0 ml/min before rHuEpo treatment to 2,079.8+/-120.7 ml/min after treatment. After hemodilution, oxygen delivery was decreased to the pretreatment value (1,710.3+/-138.1 ml/min). Fractional leg arterial oxygen extraction was unaffected at maximal exercise; hence, maximal leg oxygen uptake increased from 1,511.0+/-130.1 ml/min before treatment to 1,793.0+/-148.7 ml/min with rHuEpo and decreased after hemodilution to 1,428.0+/-111.6 ml/min. Pulmonary oxygen uptake at peak exercise increased from 3,950.0+/-160.7 before administration to 4,254.5+/-178.4 ml/min with rHuEpo and decreased to 4,059.0+/-161.1 ml/min with hemodilution (P=0.22, compared with values before rHuEpo treatment). Blood buffer capacity remained unaffected by rHuEpo treatment and hemodilution. The augmented hematocrit did not compromise peak cardiac output. In summary, in healthy humans, rHuEpo increases maximal oxygen consumption due to augmented systemic and muscular peak oxygen delivery.

[Recombinant proteins as therapeutic compounds in clinical oncology]

The in vitro production of recombinant protein molecules has fostered a tremendous interest in their clinical application for treatment and support of cancer patients. Therapeutic proteins include monoclonal antibodies, interferons, and haematopoietic growth factors. Clinically established monoclonal antibodies include rituximab (targeting CD20-positive B-cell lymphomas), trastuzumab (active in HER-2 breast and gastric cancer), and bevacizumab (blocking tumor-induced angiogenesis through blockade of vascular-endothelial growth factor and its receptor). Interferons have lost much of their initial appeal, since equally or more effective treatments with more pleasant side effects have become available, for example in chronic myelogenous leukaemia or hairy cell leukaemia. The value of recombinant growth factors, notably granulocyte colony stimulating factor (G-CSF) and erythropoietin is rather in the field of supportive care than in targeted anti-cancer therapy. Adequately powered clinical phase III trials are essential to estimate the true therapeutic impact of these expensive compounds, with appropriate selection of clinically relevant endpoints and sufficient follow-up. Monoclonal antibodies, interferons, and growth factors must also, and increasingly so, be subjected to close scrutiny by appropriate cost-effectiveness analyses to ensure that their use results in good value for money. With these caveats and under the condition of their judicious clinical use, recombinant proteins have greatly enriched the therapeutic armamentarium in clinical oncology, and their importance is likely to grow even further.

Phosphatase and tensin homolog regulates stability and activity of EphB1 receptor

Deregulation of receptor tyrosine kinases (RTKs) is linked to a broad range of cancers, stressing the necessity of studying their regulatory pathways. We and others demonstrated previously that c-Cbl is necessary for the lysosomal degradation of erythropoietin-producing hepatocellular B1 (EphB1) carcinoma and epidermal growth factor receptor (EGFR) RTKs. Moreover, the tumor suppressor phosphatase and tensin homolog (PTEN) was shown to modulate c-Cbl-dependent EGFR degradation. We therefore investigated the involvement of PTEN in EphB1 signaling and degradation. We used PTEN mutants, PTEN, and NHERF1 small interfering RNA in CHO-EphB1 and SW480 cells endogenously expressing EphB1 to delineate EphB1-PTEN interactions. PTEN was constitutively associated with c-Cbl, protecting it from degradation. EphB1 stimulation triggered ∼50% serine-threonine PTEN dephosphorylation and PTEN-Cbl complex disruption, a process requiring PTEN protein phosphatase activity. Both proteins independently translocated to EphB1, with PTEN in association with the scaffold protein NHERF1. Biologically, PTEN lipid phosphatase activity impairs EphB1-dependent cell adhesion and chemotaxis. This study demonstrates for the first time in mammalian cells that the Eph receptor and PTEN associate and influence their signaling. Moreover, it contributes to the emerging concept that PTEN regulates expression of RTKs through modulation of their degradation. Finally, it reveals a new role for PTEN protein phosphatase activity involved in this process.

Chronic excessive erythrocytosis induces endothelial activation and damage in mouse brain

Excessive erythrocytosis results in severely increased blood viscosity, which may have significant detrimental effects on endothelial cells and, ultimately, function of the vascular endothelium. Because blood-brain barrier stability is crucial for normal physiological function, we used our previously characterized erythropoietin-overexpressing transgenic (tg6) mouse line (which has a hematocrit of 0.8-0.9) to investigate the effect of excessive erythrocytosis on vessel number, structure, and integrity in vivo. These mice have abnormally high levels of nitric oxide (NO), a potent proinflammatory molecule, suggesting altered vascular permeability and function. In this study, we observed that brain vessel density of tg6 mice was significantly reduced (16%) and vessel diameter was significantly increased (15%) compared with wild-type mice. Although no significant increases in vascular permeability under normoxic or acute hypoxic conditions (8% O2 for 4 h) were detected, electron-microscopic analysis revealed altered morphological characteristics of the tg6 endothelium. Tg6 brain vascular endothelial cells appeared to be activated, with increased luminal protrusions reminiscent of ongoing inflammatory processes. Consistent with this observation, we detected increased levels of intercellular adhesion molecule-1 and von Willebrand factor, markers of endothelial activation and damage, in brain tissue. We propose that chronic excessive erythrocytosis and sustained high hematocrit cause endothelial damage, which may, ultimately, increase susceptibility to vascular disease.

[Measures for allogeneic blood conservation in surgery]

The aim of all efforts to reduce the need of allogeneic blood transfusions is to avoid associated risks. There should particularly be a favourable effect according to the rate of transfusion-transmitted virus infections and immunological side-effects. The acceptance of an individually adjusted lowest haematocrit level and the minimisation of intra-operative blood loss by the application of optimal surgical techniques are among the most essential strategies to reduce or even avoid allogeneic blood transfusions. In addition the following interventions are generally accepted: Preoperative autologous blood donation, where appropriate supported by erythropoietin Preoperative haemodilution, where appropriate supported by erythropoietin Intra- and postoperative blood salvage Topical or systemic pharmacologic interventions to accelerate haemostasis Controlled hypotension Efficacy and indication of the different measures always depend on the individual circumstances of the specific patient. Therefore one should develop an individual approach for every case. In this context the most important subjects are an optimal coordination and if required an appropriate combination of the discussed methods. Algorithms which preoperatively allow approximate calculation of expected transfusion need may be a meaningful tool to facilitate blood conservation planning. However, at the same time one must consider that all strategies to reduce allogeneic transfusion needs are also associated with particular risks. Therefore one has to weigh carefully the pros and cons prior to their application, including the possible alternative of allogeneic transfusion in one's decision making process.

Red blood cell lifespan, erythropoiesis and hemoglobin control

Erythropoietin (EPO) and iron deficiency as causes of anemia in patients with limited renal function or end-stage renal disease are well addressed. The concomitant impairment of red blood cell (RBC) survival has been largely neglected. Properties of the uremic environment like inflammation, increased oxidative stress and uremic toxins seem to be responsible for the premature changes in RBC membrane and cytoskeleton. The exposure of antigenic sites and breakdown of the phosphatidylserine asymmetry promote RBC phagocytosis. While the individual response to treatment with EPO-stimulating agents (ESA) depends on both the RBC's lifespan and the production rate, uniform dosing algorithms do not meet that demand. The clinical use of mathematical models predicting ESA-induced changes in hematocrit might be greatly improved once independent estimates of RBC production rate and/or lifespan become available, thus making the concomitant estimation of both parameters unnecessary. Since heme breakdown by the hemoxygenase pathway results in carbon monoxide (CO) which is exhaled, a simple CO breath test has been used to calculate hemoglobin turnover and therefore RBC survival and lifespan. Future research will have to be done to validate and implement this method in patients with kidney failure. This will result in new insights into RBC kinetics in renal patients. Eventually, these findings are expected to improve our understanding of the hemoglobin variability in response to ESA.

Red cell survival in relation to changes in the hematocrit: more important than you think

The management of anemia in patients with chronic renal failure has greatly improved with the availability of recombinant human erythropoietin in the late 1980s, leading to a considerable reduction in mortality and morbidity and to an improvement in quality of life. The findings from recent controlled clinical outcome trials have resulted in a rather narrow, generally accepted therapeutic hematocrit target range. However, currently available dosing algorithms do not permit achievement and maintenance of target values within the therapeutic range in many patients. One possible explanation for this failure may be the ignorance of a finite erythrocyte lifespan not integrated into most algorithms. The purpose of this article is to underline the essential role played by the erythrocyte lifespan in the erythropoietic response to recombinant human erythropoietin and to encourage the integration of this concept in the future development of computer-assisted decision support systems.

The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency

Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a reduction of extracellular water. It is unknown whether total blood volume (TBV) contributes to the reduced extracellular water in GHD. GH and insulin-like growth factor I (IGF-I) have been demonstrated to stimulate erythropoiesis in vitro, in animal models, and in growing children. Whether GH has a regulatory effect on red cell mass (RCM) in adults is not known. We analyzed body composition by bioelectrical impedance and used standard radionuclide dilution methods to measure RCM and plasma volume (PV) along with measuring full blood count, ferritin, vitamin B12, red cell folate, IGF-I, IGF-binding protein-3, and erythropoietin in 13 adult patients with GHD as part of a 3-month, double blind, placebo-controlled trial of GH (0.036 U/kg.day). TBW and lean body mass significantly increased by 2.5 +/- 0.53 kg (mean +/- SEM; P < 0.004) and 3.4 +/- 0.73 kg (P < 0.004), respectively, and fat mass significantly decreased by 2.4 +/- 0.32 kg (P < 0.001) in the GH-treated group. The baseline RCM of all patients with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/- 104 mL; P < 0.002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P < 0.006), 350 +/- 117 (P < 0.03), and 515 +/- 109 (P < 0.004) mL, respectively. The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P < 0.03) with a decrease in ferritin levels by 39.1 +/- 4.84 micrograms/L (P < 0.001) after GH treatment. Serum IGF-I and IGF-binding protein-3 concentrations increased by 3.0 +/- 0.43 (P < 0.001) and 1.3 +/- 0.15 (P < 0.001) SD, respectively, but the erythropoietin concentration was unchanged after GH treatment. No significant changes in body composition or blood volume were recorded in the placebo group. Significant positive correlations could be established between changes in TBW and TBV, lean body mass and TBV (r = 0.78; P < 0.04 and r = 0.77; P < 0.04, respectively), and a significant negative correlation existed between changes in fat mass and changes in TBV in the GH-treated group (r = -0.95; P < 0.02). We conclude that 1) erythropoiesis is impaired in GHD; 2) GH stimulates erythropoiesis in adult GHD; and 3) GH increases PV and TBV, which may contribute to the increased exercise performance seen in these patients.