Protective effect of NeuroEPO on the reproduction of diabetic rats / Efecto protector de la NeuroEPO en la reproducción de ratas diabéticas

Introduction: Pregestational diabetes constitutes a reproductive risk which requires new treatment strategies. NeuroEPO, a variant of the recombinant human erythropoietin produced in Cuba, has neuroprotective and hypoglycemic effects which can be considered for the treatment of this entity. Objective: To evaluate the protective effect of NeuroEPO on the reproduction of diabetic rats. Material and Methods: Four groups of adult female Wistar rats with streptozotocin-induced diabetes were used. During pregnancy, one group received the vehicle and the rest of the groups received different doses of NeuroEPO (0,5 mg/kg, 0,75 mg/kg, and 1 mg/kg) subcutaneously, on alternate days, for a total of six applications. A group of non-diabetic rats was used as a control group. Glycemia and reproductive variables were evaluated. For comparisons, Analysis of Variance and Fisher's Exact Test were used. There were significant differences with p-values less than 0,05. Results: The group with vehicle presented maintained hyperglycemia, fewer implantations, and embryos, and increased gestational losses. In the group receiving 0,5 mg/kg of NeuroEPO, glycemia decreased significantly and the results of the reproductive variables were similar to the group of non-diabetic rats. With higher doses of NeuroEPO, gestational losses were increased. No congenital malformations were identified in either group. Conclusions: The repeated administration of 0,5 mg/kg of NeuroEPO has a beneficial effect on the reproduction of diabetic rats, which may be associated with the reduction of hyperglycemia. Other cytoprotective mechanisms of NeuroEPO should be evaluated in future studies(AU)

Introducción: la diabetes pre-gestacional constituye un riesgo reproductivo, lo que requiere nuevas estrategias de tratamiento. Teniendo en cuenta que la NeuroEPO, una variante de la eritropoyetina recombinante humana producida en Cuba, tiene efectos neuroprotectores e hipoglicemiantes. Objetivo: evaluar el efecto protector de la NeuroEPO en la reproducción de ratas diabéticas. Material y Métodos: se utilizaron cuatro grupos de ratas Wistar hembras adultas, con diabetes inducida por estreptozotocina. Durante la gestación, un grupo recibió el vehículo y el resto diferentes dosis de NeuroEPO (0,5 mg/kg, 0,75 mg/kg y 1 mg/kg), por vía subcutánea, en días alternos, para un total de seis aplicaciones. Se empleó un grupo de ratas no-diabéticas como control. Se evaluó la glicemia y variables reproductivas. Para las comparaciones se empleó el Análisis de Varianza y la Prueba Exacta de Fisher. Las diferencias se consideraron significativas con valores de p menores que 0,05. Resultados: el grupo con vehículo presentó hiperglicemia mantenida, menor número de implantaciones y embriones, e incremento de las pérdidas gestacionales. En el grupo que recibió 0,5 mg/kg de NeuroEPO, la glicemia disminuyó de forma significativa y los resultados de las variables reproductivas fueron similares al grupo de ratas no-diabéticas. Con las dosis superiores de NeuroEPO se incrementaron las pérdidas gestacionales. No se identificaron malformaciones congénitas en ninguno de los grupos. Conclusiones: la administración reiterada de 0,5 mg/kg de NeuroEPO tiene efecto beneficioso en la reproducción de ratas diabéticas, que puede estar asociado a la reducción de la hiperglicemia. Otros mecanismos citoprotectores de la NeuroEPO deben ser evaluados en futuros estudios(AU)

Effect of Topical Erythropoietin (EPO) on palatal wound healing subsequent to Free Gingival Grafting (FGG)

Abstract Free gingival grafting, the most predictable technique to increase the keratinized gingiva, leaves an open wound on the palate and the resulting discomfort during the healing phase is a significant concern. This study was intended to evaluate the effect of topical erythropoietin on healing of the donor site. Twelve patients lacking an attached gingiva at two sites in the mandible were included. In the test group, 1 mL of gel containing erythropoietin at a concentration of 4,000 IU mL-1 was applied to the donor site, whereas the control group was treated with 2 mL of the gel alone. On the second day after surgery, the same procedure was repeated. H2O2 was used to evaluate the amount of epithelialization. Clinical healing was compared using photographs and direct examination. The EPO group showed significantly better keratinization only on day 21. Comparison of clinical healing based on direct examination revealed significantly better healing in the test group on day 28. Furthermore, inflammation in the test group was lower than in the control group on the same day. Topical application of EPO improves palatal wound healing during the third and fourth weeks after free gingival graft procedures.

Efeitos da administração de eritropoietina na dislipidemia e na hipertrofia ventricular esquerda de camundongos hiperlipidêmicos / Effects of administration of the erythropoietin in dyslipidemia and left ventricular hypertrophy of hyperlipidemic mice

O principal objetivo deste trabalho foi avaliar os efeitos da eritropoietina (EPO) no perfil lipídico e na hipertrofia ventricular esquerda (HVE) de camundongos LDLr-/- alimentados com dieta hiperlipídica, Foram utilizados vinte e quatro camundongos LDLr-/-, machos, 3 meses de idade, equinumericamente divididos em 3 grupos: Grupo S, alimentados com dieta padrão, Grupo HL, alimentados com dieta hiperlipídica (20% de gordura total e 1,25% de colesterol, 0,5 % ácido cólico), Grupo HL+EPO, alimentados com dieta hiperlipídica e tratados com EPO na dose semanal de 200UI/kg via subcutânea, Após 75 dias de experimento foram avaliadas a desenvoltura da HVE e as concentrações séricas de glicose, triglicérides (TG), colesterol total (CT) e de lipoproteínas de baixa densidade (LDL), de muita baixa densidade (VLDL), e de alta densidade (HDL) além da razão entre a massa ventricular esquerda e a massa total do animal: massa ventricular (mg)/massa do animal(g), O protocolo experimental foi aprovado pelo Comitê de Ética Experimental da Universidade sob o número 13A/2010, Ao final do período experimental, os camundongos do grupo HL apresentaram desenvolvimento de HVE com aumento nas concentrações séricas de CT, LDL, VLDL, TG e glicose e redução do HDL, quando comparados com parâmetros dos camundongos do grupo S, O uso da EPO pelo grupo HL+EPO aumentou significativamente (p<0,05) as concentrações séricas do HDL, quando comparados com o grupo HL, e preveniu a HVE, Além disso, reduziu as concentrações de CT, LDL e glicose (p<0,05), Entretanto, a EPO não foi eficiente em impedir a hipertrigliceridemia e tão pouco foi capaz de reduzir as concentrações de VLDL induzidas pela dieta HL, Em conclusão, a EPO apresentou alguns efeitos cardioprotetores, prevenindo a HVE bem como corrigindo algumas das variáveis bioquímicas induzidas pela dieta HL, Estes efeitos podem estar em parte, relacionados ao aumento das concentrações plasmáticas de HDL...

The main purpose of this work was to evaluate the effects of erythropoietin (EPO) on the lipid profile and in left ventricular hypertrophy (LVH) in mice LDLr-/-, fed a high fat diet. Were used twenty-four mice LDLr- / -, male, 3 months old, proportionally divided in 3 groups: S Group, fed with standard diet; HL Group, fed with high fat diet (20% fat total and 1.25% cholesterol, 0.5% cholic acid); HL + EPO Group, fed with high-fat diet and treated with EPO on weekly dose of 200UIkg, subcutaneously. After 75 days of experiment the development of LVH, serum concentrations of glucose, triglycerides (TG), total cholesterol (TC), and low, very low and high density lipoprotein (LDL, VLDL and HDL, respectively) in addition to the left ventricular mass ratio and the total mass of the animal (ventricular mass(mg)/total animal mass(g)) were evaluated. The experimental protocol was approved by the University Ethics Committee of the Experimental Studies under the number 13A/2010. At the end of the trial period, the mice of the HL presented development of LVH with increase in serum concentrations of CT, LDL, VLDL, TG and glucose and a decreased of HDL concentrations, when compared with parameters of mice of the Group S. The use of EPO by HL+EPO group increased serum concentrations of HDL, compared with the HL group (p<0,05) and prevented LVH. In addition, reduced the serum concentrations of TC, LDL, and glucose (p<0,05). However, EPO was not efficient in preventing the hypertriglyceridemia and still, wasn?t able to reduce VLDL concentrations induced by the diet HL. In conclusion, the EPO presented some cardio protective effects, preventing the HVE as well as correcting some of the biochemical variables diet HL-induced. These effects may be, in part, related to increased plasma concentrations of HDL...

Erythropoietin in vasospasm. From bench to bedside? / Eritropoietina no vasoespasmo. Da bancada do laboratório para a beira do leito?

Aneurysmal subarachnoid haemorrhage is one of the most deleterious acute neurological diseases. The cerebral ischemia secondary to arterial vasospasm occurring after aneurysmal subarachnoid haemorrhage is still responsible for the considerable morbidity and mortality in these patients. Besides the knowledge of basic mechanisms of cerebral vasoespasm following aneurysmal subarachnoid haemorrhage, the prophylaxis and treatment of this pathology however still remain suboptimal. There issome evidence that acute erythropoietin treatment may reduce the severity of cerebral vasospasm and eventually improve outcome in aneurysmal subarachnoid haemorrhage patients. There are underlying mechanisms extend far beyond erythropoiesis: like enhancing neurogenesis, decreasing inflammation and apoptosis inhibition. In this review the authors describe many of the biologic effects, especially experimental studies and clinical studies that reported why the erythropoietin could be beneficial topatients with aneurysmal subarachnoid haemorrhage.

A hemorragia subaracnóidea é uma das doenças neurológicas agudas mais graves. A isquemia cerebral secundária ao vasoespasmo arterial após a hemorragia ainda é responsável por considerável morbidade e mortalidade nesses pacientes. Ao lado do conhecimento dos mecanismos básicos do vasoespasmo na hemorragia subaracnóidea, a profilaxia e o tratamento dessa entidade ainda são insuficientes. Há evidências de que o uso da eritropoietina na fase aguda pode reduzir a gravidade do vasoespasmo e,eventualmente, melhorar o prognóstico desses pacientes. Há mecanismos de ação da eritropoietina que vão além da eritropoiese como neurogênese, redução da inflamação e inibição da apoptose. Nesta revisão, os autores elucidam inúmeros efeitos biológicos, principalmente aqueles demonstrados nos estudos experimentais e clínicos que descrevem por que a eritropoietina pode ser benéfica em pacientes com hemorragia subaracnóidea.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...

The impact of short daily hemodialysis on anemia and the quality of life in Chinese patients

Anemia is a frequent complication in hemodialysis patients. Compared to conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been reported to be effective in many countries except China. The aim of the present study was to determine whether sDHD could improve anemia and quality of life (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients (16 males/11 females) were converted from CHD to sDHD. All laboratory values were measured before conversion (baseline), at 3 months after conversion (sDHD1), and at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Hemoglobin concentration increased significantly from 107.4±7.9 g/L at baseline to 114.4±6.8 g/L (P<0.05) at sDHD1, and 118.3±8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement for erythropoietin decreased from 6847.8±1057.3 U/week at baseline to 5869.6±1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly from 2.05±0.13 at baseline to 2.73±0.20 (P<0.001) at sDHD1, and 2.84±0.26 (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and sDHD2, but without statistically significant differences. Physical and mental health survey scores increased in the 6 months following conversion to sDHD. sDHD may increase hemoglobin levels, decrease exogenous erythropoietin dose requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A possible mechanism for improvement of clinical outcomes may be optimized management of uremia associated with the higher efficiency of sDHD.

El tratamiento del plan AUGE (GES) de la anemia en diálisis crónica no ha sido eficaz y, probablemente, no se han aprovechado los recursos económicos destinados para ello / Results of the explicit health guaranties program to correct anemia of end stage renal disease patients in dialysis

Background: In July 2010 end stage renal disease anemia correction was incorporated to the program of explicit health guaranties of the Ministry of Health. The treatment plan included intravenous iron and erythropoietin. The prescription of these medications carne from the deriving health organizations. Aim: To describe the results of that program in 11 dialysis facilities belonging to Fresenius Medical Care (a private organization) distributed in the six Metropolitan Health Services (MHS) in Santiago, Chile. Material and Methods: We selected 328 patients who remained in dialysis treatment at least between June 2010 and March 2011 and had a packed red cell volume lower than 30%, representing the target of the Plan. The evolution of packed red cell volume and the proportion of anemic patients in the facilities from each MHS were evaluated. Results: The two above mentioned variables began to improve only in December 2010. In no MHS, with the exception of the Eastern MHS, the mean hematocrit improved to higher than 30%, nor was the proportion of anemic patients reduced to lower than 50%o. Conclusions: Treatment of anemia of end stage renal disease in dialysis, implemented by the explicit health guaranties program of the Ministry of Health, was ineffective in almost all MHS in Santiago.

Comparison of oral recombinant erythropoietin and subcutaneous recombinant erythropoietin in prevention of anemia of prematurity

Premature neonates are at risk for severe anemia and erythropoietin is the most important hormone in erythropoiesis. The aim of this study was to evaluate the influence of oral recombinant human erythropoietin [rhEPO] in proving erythropoiesis in neonates. This was a randomized clinical trial study. Thirty neonates were enrolled from September 2007 to September 2008. The first group received oral rhEPO and Fe and the second, subcutaneous rhEPO and Fe. The patients' Hb, HCT and the need to blood transfusion were recorded. We included all infants with gestational age <34 weeks, birth weight <1500 gr, without respiratory distress [O[2] Saturation> 85%, FiO[2] of 30%], full feeding tolerance so that oral Fe can be administrated. In first group [oral=PO], 65% of neonates were female and 35% were male, mean weight was 1140 g and mean GA was 32.6 weeks. In the second group [subcutaneous=SC], 42% were female and 58% were male. The mean weight was 1245 g and mean GA was 31.2 weeks and this was not statistically significant. In the first group, the mean Hb and HCT were 9.7 +/- 1.9 and 29.6 +/- 5.9 g/dl. In the second group, the figures were 12.5 +/- 1.7 and 38.8 +/- 5.1 which were statistically significant. There was no difference in the weight gain between two groups. In the first group, 3 neonates [20%] and in the second one, 1 neonate [15%] needed blood transfusion. rhEPO administration either PO or SC could prevent anemia of prematurity but SC rout was more effective

Conocimiento de los profesionales de enfermería sobre la eritropoyetina / Conhecimento dos profissionais de enfermagem sobre a eritropoetina / Nursing professionals’ knowledge about erythropoietin

Se objetivó evaluar el conocimiento de profesionales de enfermería sobre el proceso de conservación, preparación y administración de eritropoyetina (EPO). Estudio exploratorio, descriptivo, con abordaje cuantitativo. Realizado en un Centro de Diálisis, con 40 profesionales de enfermería, entre enero y marzo de 2009, utilizando un cuestionario. Los aspectos técnicos fueron considerados. Sobre la interacción de la EPO con la presión arterial, 87,5 por ciento posee conocimientos inadecuados; sólo el 32 por ciento conocían la temperatura ideal para conservación del medicamento y 52,5 por ciento creía que éste debe ser retirado del refrigerador de 15 a 30 minutos antes de la administración; la vía más citada fue la endovenosa. Entre los cuidados anteriores a la administración, la inspección de fecha de vencimiento fue el más frecuente; 57,5 utilizan jeringa exclusiva para administración y 95 por ciento acostumbra registrar la administración del fármaco.

Objetivou-se avaliar o conhecimento dos profissionais de enfermagem sobre o processo de conservação, preparo e administração da eritropoetina (EPO). Estudo exploratório descritivo, com abordagem quantitativa. Realizado em um Centro de Diálise, com 40 profissionais de enfermagem, entre janeiro e março de 2009, utilizando um questionário. Os aspectos éticos foram considerados. Sobre a interação da EPO com a pressão arterial do paciente, 87,5 por cento possuem conhecimento inadequado; somente 32 por cento conheciam a temperatura ideal para a conservação do medicamento e 52,5 por cento acreditam que este deve ser retirado do refrigerador de 15 a 30 minutos antes da administração; a via mais citada foi a endovenosa. Entre os cuidados antes da administração, a inspeção do prazo de validade foi o mais freqüente; 57,5 por cento utilizam seringa exclusiva para administração e 95 por cento costumam registrar a administração do fármaco.

This study was performed with the objective to evaluate the knowledge that nursing professionals have about the process of preserving, preparing and administering erythropoietin (EPO). This exploratory, descriptive study used a quantitative approach. It was performed at a Dialysis Center, from January to March 2009, and consisted on applying a questionnaire to 40 nursing professionals. All ethical aspects were taken into consideration. About the interaction of EPO with the patients' blood pressure, 87.5 percent had inadequate knowledge; only 32 percent knew the ideal temperature to preserve the drug, and 52.5 percent believe that it should be removed from the refrigerator about 15 to 30 minutes before its administration; intravenous administration was the most reported. Among the care before the administration, the most frequent was checking the expiration date; 57.5 percent used exclusive syringe for the administration and 95 percent usually register having administered the drug.

Proteção renal com eritropoetina em modelo de isquemia renal no rato / Kidney protection with erythropoietin in rat ischemia model

A isquemia e reperfusão (I/R) é a principal causa de lesão renal aguda após transplante renal. Hiperglicemia está associada a diminuição da tolerância à isquemia e aumento da gravidade da lesão renal da I/R. Eritropoetina administrada antes da isquemia/reperfusão renal (pré-condicionamento da eritropoetina) exerce efeito renoprotetor em animais normoglicêmicos, mas, este efeito, ainda não foi estudado em animais com hiperglicemia transitória. O objetivo desta pesquisa foi investigar o efeito da eritropoetina na lesão de isquemia/reperfusão renal em ratos com hiperglicemia transitória. Vinte e oito ratos Wistar machos (>300g) foram anestesiados com isoflurano a 3%, intubados e submetidos à ventilação mecânica com isoflurano a 1,5%. Artéria carótida e veia jugular foram cateterizadas. Dióxido de carbono em final de expiração, concentração inspirada e expirada de gás anestésico, pressão arterial invasiva e temperatura retal foram continuamente monitorizados (Datex, AS3). A temperatura retal foi mantida entre 36oC-38oC. Os animais foram divididos aleatoriamente em quatro grupos e todos receberam glicose 2,5 g.kg-1 por via intraperitoneal, sendo submetidos a laparotomia mediana e nefrectomia direita (Grupo S – sham - n=6). Os demais animais foram submetidos a 25 minutos de isquemia renal esquerda por clampeamento da artéria renal esquerda (Grupos ISO, EA e EM). 30 minutos antes da isquemia renal esquerda o Grupo ISO (n=6) recebeu soro fisiológico, o Grupo EA (n=8) eritropoetina 5000 UI.kg- 1 e o Grupo EM (n=8) eritropoetina 600 UI.kg-1por via intravenosa. A pressão arterial média (PAM) e a temperatura foram avaliadas a cada 10 minutos. Os valores plasmáticos da glicose e da creatinina foram determinados no inicio (M1) e no final do experimento (M2)...

Ischemia and reperfusion (I/R) injury is the leading cause of acute renal injury following renal transplantation. Hyperglycemia is associated with decreased tolerance to ischemia and increases the severity of renal I/R injury. Erythropoietin administered before renal ischemia/reperfusion (erythropoietin preconditioning) may exert some renoprotective effect in normoglycemic animals. However, such effect has not been studied in transiently hyperglycemic animals. This study aimed to examine the effect of erythropoietin preconditioning on renal ischemia /reperfusion injury in transiently hyperglycemic rats. Twenty- eight male Wistar rats weighting more than 300g were anesthetized with 3% isoflurane. After tracheal intubation, the animals were mechanically ventilated with air and 1.5 % isoflurane. Carotid artery and jugular vein were cannulated. End-tidal carbon dioxide partial pressure, inspired and expired anesthetic gas concentrations, direct arterial pressure and rectal temperature were continuously measured. Glucose 2,5 g.kg-1 was administered intraperitoneally to induce hyperglycemia. Rectal temperature was kept between 360C-380C. Animals were submitted a midline laparotomy and right nephrectomy. Animals were randomly allocated into four groups: S, sham, (n=6) underwent only right nephrectomy, no left kidney ischemia/reperfusion. Group ISO (n=6), underwent a 25-minute period of left renal artery clamping, not preceded by erythropoietin preconditioning dose, Group EH (n = 8), received high-dose erythropoietin (5000 UI.kg-1 i.v.), 30 minutes before a 25 minutes period of left renal artery clamping; Group EL (n = 8) received low-dose erythropoietin (600 UI.kg-1, i.v.) 30 minutes before a 25-minute period of left renal artery clamping. Creatinine and glucose serum levels were determined at the start (M1), at the end (M2), and 24 hours after the experiment (M3)...

Postoperative High-Dose Intravenous Iron Sucrose with Low Dose Erythropoietin Therapy after Total Hip Replacement

Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B12, vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.

Post-treatment Effects of Erythropoietin and Nordihydroguaiaretic Acid on Recovery from Cisplatin-induced Acute Renal Failure in the Rat

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.

Doses intermitentes de estatina em pacientes em hemodiálise com LDL-colesterol espontaneamente baixo / Intermittent doses of statin in hemodialysis patients with spontaneous low LDL cholesterol levels

FUNDAMENTO: A mortalidade na diálise continua elevada e ocorre principalmente por causas cardiovasculares. A inflamação participa da gênese da aterosclerose acelerada, calcificação vascular, desnutrição e anemia, e tem enorme impacto na sobrevida destes pacientes. As estatinas, através dos seus efeitos pleiotrópicos, podem representar uma opção terapêutica para atenuação do processo inflamatório crônico dos pacientes em hemodiálise. OBJETIVO: Avaliar os efeitos de uma baixa dose de sinvastatina sobre marcadores inflamatórios, parâmetros hematimétricos e nutricionais de pacientes em hemodiálise. MÉTODOS: Pacientes em hemodiálise clinicamente estáveis foram divididos, segundo os níveis basais de LDL-colesterol, em um grupo com níveis abaixo (Grupo 1) e outro com níveis iguais ou superiores a 100 mg/dl (Grupo 2) e tratados com sinvastatina por oito semanas. O Grupo 1 recebeu apenas 20 mg após cada sessão de diálise (dose intermitente), enquanto o Grupo 2 recebeu 20 mg/dia. Dados laboratoriais, índice de resistência a eritropoetina e parâmetros nutricionais foram obtidos antes e após o tratamento. RESULTADOS: Houve redução significativa e equivalente dos níveis de proteína C-reativa em ambos os grupos (35,97±49,23 por cento vs 38,32±32,69 por cento, p=0,86). No Grupo 1 também houve tendência a queda da resistência a eritropoetina (228,6±16,2 vs 208,9±16,2, p=0,058) e melhora dos parâmetros hematimétricos (hematócrito: 33,1±5,9 por cento vs 36,1±4,5 por cento, p=0,021). CONCLUSÃO: A dose intermitente mostrou-se tão eficaz quanto a dose usual em reduzir os níveis de proteína C-reativa e resistência a eritropoetina, além de melhorar os parâmetros hematimétricos, apontando para uma importante redução do risco cardiovascular avaliado por esses parâmetros.

BACKGROUND: Mortality in dialysis patients remains high and is due mainly to cardiovascular causes. Inflammation has a role in the genesis of accelerated atherosclerosis, vascular calcification, malnutrition and anemia, and a huge impact on the survival of these patients. The pleiotropic effects of statins can be a therapeutic option for reducing chronic inflammatory processes of patients undergoing hemodialysis. OBJECTIVE: To evaluate the effects of low doses of simvastatin on inflammatory markers, hematimetric and nutritional parameters of patients undergoing hemodialysis. METHODS: Clinically-stable patients undergoing hemodialysis were classified according to their baseline LDL-cholesterol levels in two groups: those with levels below 100mg/dl (Group 1) and those with levels equal to or greater than 100mg/dl (Group-2), and were treated with simvastatin during eight weeks. Group 1 received 20mg only after each session of hemodialysis (intermittent dose), whereas Group 2 received 20mg/daily. Laboratory data, erythropoietin resistance index and nutritional parameters were obtained before and after treatment. RESULTS: A significant and equivalent reduction in C-reactive protein levels in both groups was observed (35.97±49.23 percent vs 38.32±32.69 percent, p=0.86). In group 1, there was also a tendency towards reduced resistance to erythropoietin (228.6±16.2 vs 208.9±16.2, p=0.058) and improvement of hematimetric parameters (hematocrit: 33.1±5.9 percent vs 36.1±4.5 percent, p=0.021). CONCLUSION: Intermittent doses proved to be as effective as the usual dose in reducing C-reactive protein levels and resistance to erythropoietin, besides improving the hematimetric parameters, indicating an important reduction of the cardiovascular risk evaluated by these parameters.

Enteral erythropoietin increases plasma erythropoietin level in preterm infants: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of enteral administration of recombinant human erythropoietin (rhEPO) on serum level of erythropoietin and erythropoiesis in preterm infants. STUDY DESIGN: Randomized controlled trial. SETTING: Level III NICU. SUBJECTS: 16 preterm infants less than 34 wk with birth weight less than 1800 g. INTERVENTION: Enteral rhEPO 400 U/kg, three times/week, plus FeSO4,3-6 mg/Kg/day ( Study group, n = 7) or FeSO4 only (Control group, n = 9). OUTCOME MEASURES: Hemoglobin, serum erythropoietin (EPO), reticulocyte count, and serum ferritin levels, measured at baseline, after 10 days and at discharge. RESULTS: Mean birth weight and gestational age for the Study and the Control groups were 1328.5 +/- 267.4 vs. 1392.8 +/- 196.7 g and 30.7 +/- 2.5 vs. 30.2 +/- 0.9 weeks, respectively. At discharge, there was no difference in hemoglobin or hematocrit but the reticulocyte counts were significantly higher in the Study group (1.4 +/- 0.7 vs. 0.7 +/- 0.4, P = 0.03). Serum erythropoietin level was significantly higher in the Study group (18 +/- 11 vs. 8.6 +/- 3.9 mU/mL, P = 0.006). Conversely, serum ferritin level was lower in the study group but did not achieve statistical significance. CONCLUSIONS: Enteral administration of rhEPO in preterm infants resulted in increase in serum erythropoietin and reticulocyte counts at the time of discharge without significantly affecting hemoglobin or hematocrit.

Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n=167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P=0.038 and P=0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P=0.005 and P=0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10+/-5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97+/-4.90 and 15.12+/-7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.

[ effect of intravenous Iron therapy on haemoglobin level and optimization of erythropoietin therapy in haemodialysis patients]

Decrease in production of erythropoietin has been noted as one of the main factors causing anemia in ESRD patients, and administration of recombinant human erythropoietin [rhEPO] has been used to correct the anemia. Iron deficiency, including functional iron deficiency, limits the efficacy of rhEPO therapy in ESRD patients. This study examined the effects of maintenance intravenous iron sucrose [Venofer] on haemoglobin level and, optimization of erythropoietin therapy. Forty eight haemodialysis patients with haemoglobin level<9 gr/dl who were dialyzed three times weekly went under the study. Two thousands units of rhEPO were given subcutaneously at the end of each dialysis for seven weeks. At the end of the seventh week, those with haemoglobin level<9 gr/dl and with ferritin level <200 ng/dl [29 patients] were chosen for intravenous administration of 100 mg Venfor during the next five consecutive haemodialysis while maintaining the rhEPO dose at 2000 units with each dialysis. A week after the last dose of Venofer, haemoglobin and serum ferritin were determined. Average haemoglobin level among the patients before administration of rhEPO was 7.5 gr/dl. After seven weeks of subcutaneous rhEPO at 2000 units with each haemodialysis, the average haemoglobin level raised to 8.5 gr/dl. The effect of maintenance IV Venofer was an increase in average haemoglobin level to 10.4 gr/dl. The same effect was seen on the ferritin level. The ferritin level of 131 ng/dl increased to 237 ng/dl a week after last dose of IV venofer. Intravenous [IV] iron improves haemoglobin response and, thus, optimizes rhEPO therapy