Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.228
Filtrar
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1155-1159, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801712

RESUMO

OBJECTIVE: To evaluate the therapeutic effect of Qingshen Granules on renal anemia in patients with damp-heat syndrome and explore the mechanisms in light of inflammation/hepcidin axis and iron metabolism. METHODS: Sixty patients with renal anemia and dampness-heat syndrome were randomized into control group (n=30) and treatment group (n=30). All the patients were given routine treatment, and the patients in the treatment group received additional treatment with Qingshen Granules (3 times a day). After 12 weeks of treatments, the patients were examined for changes in the integral value of TCM syndrome, serum creatinine (Scr), glomerular filtration rate (eGFR), hemoglobin (HGB), hematocrit (HCT), red blood cell (RBC) count, interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), ferritin, growth differentiation factor-15 (GDF-15), serum iron (SI), total iron binding capacity (TIBC), transferrin saturation (TAST), soluble transferrin receptor (sTfR) and ferritin levels. RESULTS: After the treatment, the scores of TCM syndrome were significantly improved in the treatment group and were better than those in the control group (P=0.000). Scr and eGFR were improved in both groups after the treatment. The levels of HGB, HCT and RBC were all improved in the two groups after treatment, and the improvements were more obvious in the treatment group (P=0.002, 0.002, and 0.017, respectively). The levels of IL-6, hs-CRP, hepcidine and GDF-15 were all lowered in the two groups after the treatment, and they were all significantly lower in the treatment group than in the control group (all P=0.000). The treatments increased the levels of SI and TAST in both of the groups, and compared with those in control group, the levels of TIBC, sTfR and ferritin were significantly lowered in the treatment group after the 12-week treatment (P=0.000). CONCLUSIONS: Qingshen granules can effectively improve renal anemia in patients with damp-heat syndrome possibly by improving iron metabolism through alleviation of inflammation and reduction of hepcidine level.


Assuntos
Anemia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hepcidinas/metabolismo , Inflamação/tratamento farmacológico , Ferro/metabolismo , Humanos
4.
G Ital Nefrol ; 36(5)2019 Sep 24.
Artigo em Italiano | MEDLINE | ID: mdl-31580542

RESUMO

Over the past two decades it has emerged that, in addition to erythropoietic activity, erythropoietin (EPO) has numerous other functions, including neuro-protective, anti-apoptotic, antioxidant, angiogenetic and immunomodulatory ones. EPO interacts with two different forms of its receptor (EPOR): a homodimer receptor, responsible for the erythropoietic effects, and a heterodimer receptor, responsible for the non-erythropoietic effects. The effects on the heterodimer receptor are responsible for EPO-induced prolongation of organ transplant survival in mice and humans. The development of new molecules that selectively target the heterodimer EPOR is allowing to test the effect of long-term treatments, without the possible complications related to the increased hematocrit.


Assuntos
Eritropoese/fisiologia , Eritropoetina/fisiologia , Sobrevivência de Enxerto/fisiologia , Receptores da Eritropoetina/fisiologia , Imunidade Adaptativa , Anemia/tratamento farmacológico , Anemia/etiologia , Animais , Hipóxia Celular/fisiologia , Eritropoetina/genética , Eritropoetina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Coração/efeitos dos fármacos , Humanos , Imunidade Celular , Imunidade Inata , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos , Sistema Nervoso/metabolismo , Transplante de Órgãos , Ratos , Receptores de Fator Estimulador de Colônias/fisiologia , Proteínas Recombinantes/uso terapêutico , Insuficiência Renal Crônica/complicações , Retina/metabolismo
5.
Int J Mol Sci ; 20(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600973

RESUMO

Anemia is a severe complication in patients with chronic kidney disease (CKD). Treatment with exogenous erythropoietin (EPO) can correct anemia in many with CKD. We produced 5/6-nephrectomized rats that became uremic and anemic at 25 days post surgery. Injection of the anemic 5/6-nephrectomized rats with 2.8 mg zinc/kg body weight raised their red blood cell (RBC) levels from approximately 85% of the control to 95% in one day and continued for 4 days. We compared the effect of ZnSO4 and recombinant human erythropoietin (rHuEPO) injections on relieving anemia in 5/6-nephrectomized rats. After three consecutive injections, both the ZnSO4 and rHuEPO groups had significantly higher RBC levels (98 ± 6% and 102 ± 6% of the control) than the saline group (90 ± 3% of the control). In vivo, zinc relieved anemia in 5/6-nephrectomized rats similar to rHuEPO. In vitro, we cultured rat bone marrow cells supplemented with ZnCl2, rHuEPO, or saline. In a 4-day suspension culture, we found that zinc induced erythropoiesis similar to rHuEPO. When rat bone marrow cells were supplement-cultured with zinc, we found that zinc stimulated the production of EPO in the culture medium and that the level of EPO produced was dependent on the concentration of zinc supplemented. The production of EPO via zinc supplementation was involved in the process of erythropoiesis.


Assuntos
Anemia/etiologia , Suplementos Nutricionais , Eritropoetina/farmacologia , Proteínas Recombinantes/farmacologia , Insuficiência Renal Crônica/complicações , Zinco/administração & dosagem , Anemia/sangue , Anemia/tratamento farmacológico , Animais , Biomarcadores , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Modelos Animais de Doenças , Índices de Eritrócitos/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Humanos , Ratos , Sulfato de Zinco/administração & dosagem
6.
Int Urol Nephrol ; 51(10): 1855-1865, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485910

RESUMO

BACKGROUND: Parental iron is used to optimize hemoglobin and enhance erythropoiesis in end-stage renal disease along with erythropoietin-stimulating agents. Safety of iron has been debated extensively and there is no definite evidence whether parenteral iron increases the risk of infections and mortality. We performed this meta-analysis to evaluate the incidence of infectious complications, hospitalizations and mortality with use of parenteral iron. METHODS: Medical electronic databases [PubMed, EMBASE, Scopus, Web of Science, and cochrane central register for controlled clinical trials (CENTRAL)] were queried for studies that investigated the association between intravenous iron administration and infection in hemodialysis patients. 24 studies (8 Randomized control trials (RCTs) and 16 observational studies) were considered for qualitative and quantitative analysis. RESULTS: All-cause mortality Data from 6 RCTs show that high-dose IV iron conferred 17% less all-cause mortality compared to controls; however, this outcome was not statistically significant (OR = 0.83, CI [0.7, 1.01], p = 0.07). Nine observational studies were pooled under the random effects model due to significant heterogeneity (I2 = 83%, p < 0.001). The overall HR showed increased risk of all-cause mortality in the high-dose group but was statistically non-significant (HR = 1.1, CI [1, 1.22], p = 0.06). Infections Four RCTs with no heterogeneity among their data (I2 = 0%, p = 0.61). Under the fixed effect model, there was no difference in the infection rate between high-dose iron and control group (OR = 0.97, CI [0.82, 1.16], p = 0.77); eight observational studies with significant heterogeneity and utilizing random effects model. Summary HR showed increased yet non-significant risk of infection in the high-dose group (HR = 1.13, CI [0.99, 1.28], p = 0.07) Hospitalization 1 RCT and six observational studies provided data for the rate of all-cause hospitalization. There was marked heterogeneity among observational studies. RCT showed no significant difference between high-dose iron and controls in the rate of hospitalization (OR = 1.03, CI [0.87, 1.23], p = 0.71). Summary HR for observational data showed increased rate of hospitalization in the high-dose group; however, this effect was not statistically significant (HR = 1.11, CI [0.99, 1.24], p = 0.07). Cardiovascular events One RCT compared the rate of adverse cardiovascular events between high-dose and low-dose iron. No significant difference was observed between the two groups (22.3% vs 25.6%, p = 0.12). Six heterogeneous observational studies (I2 = 65%, p < 0.001) reported on the rate of cardiovascular events. No significant difference was observed between high-dose iron and controls (HR = 1.18, CI [0.89, 1.57], p = 0.24). CONCLUSION: High-dose parenteral iron does not seem to be associated with higher risk of infection, all-cause mortality, increased hospitalization or increased cardiovascular events on analysis of RCTs. Observational studies show increased risk for all-cause mortality, infections and hospitalizations that were not statistically significant and were associated with significant heterogeneity.


Assuntos
Anemia/tratamento farmacológico , /mortalidade , Ferro/administração & dosagem , Ferro/efeitos adversos , Administração Intravenosa , Anemia/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Falência Renal Crônica/complicações , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Chin J Nat Med ; 17(7): 535-544, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31514985

RESUMO

The aim of this study is to investigate the protective effects of a small molecular fraction (SMF) of Polygoni multiflori Radix Praeparata (PMRP) in a cyclophosphamide (CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor (GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay (ELISA); The level of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase (GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.


Assuntos
Anemia/tratamento farmacológico , Ciclofosfamida/toxicidade , Hematopoese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Polygonum/química , Anemia/induzido quimicamente , Animais , Antioxidantes/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Masculino , Camundongos Endogâmicos ICR , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Timo/efeitos dos fármacos , Timo/metabolismo
8.
Transfus Apher Sci ; 58(4): 449-452, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31395426

RESUMO

Ghosal hematodiaphyseal dysplasia (GHDD) is an autosomal recessive inherited disorder associated with biallelic mutations in the TBXAS1 gene located on the chromosome 7q33-34, which encodes thromboxane-A-synthase. GHDD is characterized by defective hematopoiesis due to bone marrow fibrosis and metadiaphyseal dysplasia of long bones. The accurate diagnosis of this rare syndrome is critical since it reduces the need of blood transfusions by corticosteroid therapy, leading to a significant improvement in anemia and bone changes. The aim of this study is to report two adult siblings diagnosed as GHDD, who admitted with pancytopenia and treated with steroids treatment in adult hematology clinic.


Assuntos
Anemia Refratária , Anemia , Doenças Autoimunes , Cromossomos Humanos Par 7/genética , Mutação , Osteocondrodisplasias , Irmãos , Adulto , Anemia/diagnóstico por imagem , Anemia/tratamento farmacológico , Anemia/genética , Anemia Refratária/diagnóstico por imagem , Anemia Refratária/tratamento farmacológico , Anemia Refratária/genética , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Humanos , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/tratamento farmacológico , Osteocondrodisplasias/genética
9.
Eur J Med Res ; 24(1): 28, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405381

RESUMO

BACKGROUND: Preoperative anemia is relatively common in patients undergoing primary total knee arthroplasty (TKA), and is associated with higher medical costs due to blood transfusions. METHODS: We aimed to discuss the efficiency of tranexamic acid (TXA) administration for blood loss control in preoperatively anemic patients undergoing primary TKA. We retrospectively reviewed the clinical data regarding a consecutive series of primary unilateral TKA patients with preoperative anemia. Patients were divided into TXA group (received TXA peri-operatively) and control group (did not receive TXA). Outcome measures included drainage volume; hemoglobin, and hematocrit levels recorded preoperatively and over the first 5 days postoperatively; amount of allogeneic blood transfusion; and prevalence of thrombosis. RESULTS: Ninety-six patients from 996 cases were included in the study. Demographics, general health condition, and preoperative conditions were comparable between the two groups. However, significantly lower drainage volume (P < 0.001), hidden blood loss (P < 0.001), and allogeneic blood transfusion volume (χ = 4.00, P = 0.046) were noted in TXA group. The hemoglobin and hematocrit levels were significantly higher in TXA group on the first postoperative day (P = 0.006), but overall the drop in hemoglobin and hematocrit levels over the first 5 days postoperatively was similar between the groups (P = 0.763), as was the incidence of thromboembolism events (P = 0.794). CONCLUSION: TXA has a positive role for patients with preoperative anemia in primary total knee arthroplasty. In patients with mild preoperative anemia, TXA decreases hidden blood loss and the need for allogeneic blood transfusion, which mainly appears effective on the first postoperative day of TKA.


Assuntos
Anemia/tratamento farmacológico , Anemia/etiologia , Artroplastia do Joelho/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Ácido Tranexâmico/uso terapêutico , Idoso , Perda Sanguínea Cirúrgica , Distribuição de Qui-Quadrado , Feminino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Masculino , Ácido Tranexâmico/administração & dosagem
10.
J Clin Neurosci ; 69: 38-42, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31447360

RESUMO

BACKGROUND: Cognitive dysfunction potentially affecting up to 60% of CKD patients. GSK-3ß plays a key role in the pathogenesis of AD and Cognitive dysfunction, contributing to Aß production and Aß-mediated neuronal death by phosphorylating tau inducing hyperphosphorylation in paired helical filaments. However, studies have shown that plasma p-Tau181 is more specific for AD and cognitive dysfunction. Anemia is a vital risk factor for cognitive dysfunction in CKD patients. EPO is usually to treat anemia in CKD and also improved in cognitive function. The aim of the study is to correlate between the impacts of rHuEPO therapy on platelet GSK3ß expression, plasma Aß, total Tau, p-Tau 181 levels and neuropsychological assessments total scores in CKD patients with Cognitive dysfunction. METHODS: The subjects, 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction patients. To correlate abnormal proteins with neuropsychological tests scoring in CKD with cognitive dysfunction subjects after the six months rHuEPO therapy. RESULTS: The p < 0.05 is considered as statistically significant. Pearson and Spearman correlation coefficient was used to determine the potential relationship between abnormal proteins with neuropsychological tests scoring in respective experimental groups. CONCLUSIONS: The use of abnormal protein levels, preferably in association with neuropsychological assessment total scores, appears to be a potential tool that can improve the CKD with cognitive dysfunction diagnosis. In post rHuEPO treatment, the altered protein abnormalities and neuropsychological assessment scores were retrieved significantly compared to pre treatment determined the clinical usefulness of rHuEpo as supplemental therapeutic agent in cognitive dysfunction in CKD.


Assuntos
Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Eritropoetina/uso terapêutico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Adulto , Peptídeos beta-Amiloides/sangue , Anemia/tratamento farmacológico , Anemia/etiologia , Biomarcadores/sangue , Feminino , Glicogênio Sintase Quinase 3 beta/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Proteínas Recombinantes/uso terapêutico , Proteínas tau/sangue
11.
Transfus Apher Sci ; 58(4): 416-421, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31281092

RESUMO

Anemia in elderly (AE), though often mild, is quite common and independently associated with important clinical outcomes, including decreased quality of life, risk of falls and fractures, cognitive decline, increased length of hospital stay, and even mortality. AE is generally overlooked, and hence undertreated, especially when comorbidities distract the attention of physicians and caregivers. This also partially reflects difficulties in dissecting the cause(s) of AE, which is typically multifactorial, as well as our limited diagnostic approach often categorizing AE as apparently "unexplained". Therapeutic approaches have been traditionally limited to transfusions, or supplementation with hematinics, including group B vitamins and iron. The latter has been largely underutilized, because of missing diagnosis of iron deficiency using inappropriate laboratory thresholds, as well as complex schedule and adverse effects associated with traditional preparations. After decades of stagnation, new oral and intravenous iron preparations look promising, particularly in the elderly. Moreover, a number of innovative anti-anemic drugs, like hepcidin modulators, Hypoxia Inducible Factor (HIF) stabilizers, and activin type II receptor agonists are entering the clinical arena and may substantially improve our therapeutic armamentarium to AE in the near future.


Assuntos
Anemia , Serviços de Saúde para Idosos , Hematínicos/uso terapêutico , Distúrbios do Metabolismo do Ferro , Ferro , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/tratamento farmacológico , Humanos , Ferro/deficiência , Ferro/uso terapêutico , Distúrbios do Metabolismo do Ferro/sangue , Distúrbios do Metabolismo do Ferro/tratamento farmacológico
12.
N Engl J Med ; 381(11): 1001-1010, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340089

RESUMO

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).


Assuntos
Anemia/tratamento farmacológico , Glicina/análogos & derivados , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Acidose/induzido quimicamente , Adulto , Idoso , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue
13.
N Engl J Med ; 381(11): 1011-1022, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340116

RESUMO

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).


Assuntos
Anemia/tratamento farmacológico , Epoetina alfa/uso terapêutico , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Análise de Variância , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Epoetina alfa/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Hipertensão/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia
14.
Crit Rev Oncol Hematol ; 141: 54-72, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228649

RESUMO

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders characterized by cytopenias and progression to acute myeloid leukemia (AML). Although several treatments for MDS are available, the mainstay of therapy for most patients remains supportive care. This includes red blood cell (RBC) transfusion to correct anemia, which leads to iron overload. RBC transfusion dependence and iron overload portend inferior overall survival. Some studies indicate that iron chelation therapy (ICT) may have beneficial effects on clinical endpoints in MDS; however, these data are from non-randomized trials and the validity of the results is vigorously debated. A consistent observation in clinical studies of ICT in MDS has been hematologic improvement (HI) in some patients, including a reduction in RBC transfusion requirements and even transfusion independence. Here, we review data on HI with ICT in lower risk MDS, preclinical data examining mechanisms by which HI may occur, and identify areas for future investigation.


Assuntos
Terapia por Quelação , Transfusão de Eritrócitos/efeitos adversos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/prevenção & controle , Síndromes Mielodisplásicas/terapia , Anemia/tratamento farmacológico , Anemia/etiologia , Transfusão de Sangue/métodos , Terapia por Quelação/métodos , Transfusão de Eritrócitos/métodos , Humanos , Ferro/sangue , Sobrecarga de Ferro/etiologia , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Reação Transfusional/sangue , Reação Transfusional/prevenção & controle
15.
BioDrugs ; 33(4): 373-389, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31161461

RESUMO

BACKGROUND: Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar). OBJECTIVE: The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology. METHODS: We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence. RESULTS: We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses. CONCLUSION: Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.


Assuntos
Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Anemia/induzido quimicamente , Neutropenia Febril Induzida por Quimioterapia/etiologia , Epoetina alfa/uso terapêutico , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Pak J Pharm Sci ; 32(2 (Supplementary)): 765-768, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31103969

RESUMO

Anemia is very common among end stage patients with chronic renal failure (CRF). In this investigation, hematological parameters were examined in patients with end stage chronic renal failure from Khartoum, Sudan. A total of 70 patients and additional 30 healthy subjects were included in the study. All patients were under erythropoietin therapy whereas 42% were using iron supplements. The results showed that about 98% of CRF patients had anemia. Normocytic normochromic anemia was the most common type (94%) while few were suffering from microcytic hypochromic (6%) anemia. Low levels of hemoglobin, red blood cell count, hematocrits, serum iron, serum ferritin, and platelet counts were observed in the patient group compared to healthy controls (P<0.01). However, MCV, MCH and MCHC were not different between the two groups (P > 0.05). Moreover, no significant differences in all hematological parameters between patients with and without iron supplements were observed except for hemoglobin. In conclusion, anemia is common among end stage CRF in Sudan in spite of erythropoietin and iron therapy.


Assuntos
Anemia/etiologia , Ferro/uso terapêutico , Falência Renal Crônica/sangue , Adulto , Anemia/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Estudos de Casos e Controles , Suplementos Nutricionais , Eritropoetina/uso terapêutico , Feminino , Hematócrito , Hemoglobinas/análise , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sudão
18.
Chin J Nat Med ; 17(4): 275-290, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31076131

RESUMO

Danggui Buxue Tang (DBT) is a famous Chinese medicinal decoction. Mechanism of DBT action is wide ranging and unclear. Exploring new ways of treatment with DBT is useful. Sprague-Dawley(SD) rats were randomly divided into 3 groups including control (NC, Saline), the DBT (at a dose of 8.10 g-1), and blood deficiency(BD) (Cyclophosphamide (APH)-andCyclophosphamide(CTX)-induced anaemia). A metabolomics approach using Liquid Chromatography-Quadrupole-Time-of-Flight/Mass Spectrometry (LC/Q-TOFMS) was developed to perform the plasma metabolic profiling analysis and differential metaboliteswerescreened according to the multivariate statistical analysiscomparing the NC and BD groups, andthe hub metabolites were outliers with high scores of the centrality indices. Anaemia disease-related protein target and compound of DBT databases were constructed. The TCMSP, ChemMapper and STITCH databases were used to predict the protein targets of DBT. Using the Cytoscape 3.2.1 to establish a phytochemical component-target protein interaction network and establish a component, protein and hub metabolite protein-protein interaction (PPI) network and merging the three PPI networks basing on BisoGenet. The gene enrichment analysis was used to analyse the relationship between proteins based on the relevant genetic similarity by ClueGO. The results shown DBT effectively treated anaemia in vivo. 11 metabolic pathways are involved in the therapeutic effect of DBT in vivo; S-adenosyl-l-methionine, glycine, l-cysteine, arachidonic acid (AA) and phosphatidylcholine(PC) were screened as hub metabolites in APH-and CTX-induced anaemia. A total of 288 targets were identified as major candidates for anaemia progression. The gene-set enrichment analysis revealed that the targets are involved in iron ion binding, haemopoiesis, reactive oxygen species production, inflammation and apoptosis. The results also showed that these targets were associated with iron ion binding, haemopoiesis, ROS production, apoptosis, inflammation and related signalling pathways. DBT can promote iron ion binding and haemopoiesis activities, restrain inflammation, production of reactive oxygen, block apoptosis, and contribute significantly to the DBT treat anaemia.


Assuntos
Anemia/tratamento farmacológico , Anemia/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Metaboloma/efeitos dos fármacos , Metabolômica , Anemia/sangue , Anemia/induzido quimicamente , Animais , Cromatografia Líquida , Ciclofosfamida/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas em Tandem
19.
Acta Haematol ; 142(1): 37-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970356

RESUMO

Posttransplantation anemia (PTA) is common among kidney transplant patients. Early PTA is usually defined as anemia which develops up to 6 months after transplantation, and late PTA is defined as anemia which develops after 6 months. There are multiple causes, with iron deficiency being the major contributor. The occurrence of late PTA has been associated with impaired graft function. Early PTA has been shown to be a predictor of late PTA. PTA is associated with reduced mortality, reduced graft survival, and a decline in GFR. The association with mortality is related to the severity of the anemia and to specific causes of anemia. Treatment of PTA should probably begin as soon as possible after kidney transplantation. The optimal target hemoglobin level in kidney transplant recipients with anemia is higher than recommended in chronic kidney disease and should probably be up to 12.5-13 g/dL. In order to achieve this target, appropriate treatment with erythropoiesis-stimulating agents (ESA) and iron is indicated.


Assuntos
Anemia/tratamento farmacológico , Transplante de Rim , Anemia/epidemiologia , Anemia/etiologia , Ensaios Clínicos como Assunto , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Hematínicos/uso terapêutico , Humanos , Ferro/administração & dosagem , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia
20.
Biomed Pharmacother ; 112: 108740, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970527

RESUMO

AIM: Anemia of chronic disease is considered the most common extra-articular manifestation of rheumatoid arthritis (RA). The present study aimed to investigate the effect of etanercept (anti-tumor necrosis factor) on anemia and hepcidin gene expression in a rat model of RA. METHOD: Rheumatoid arthritis was induced in rats by Freund Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil, subcutaneously) on days (0, 30 and 40). Etanercept was administered subcutaneously at a dose of (0.3 mg/kg 3 times/week). Arthritis parameters, erythrocytic indices, iron profile, serum TNF-α, serum IL-6 and hepatic RT-PCR hepcidin expression were assessed. RESULTS: FCA-rats developed arthritis and anemia, with significant increase of serum TNFα and IL-6 levels, and of hepcidin gene expression. In RA-rats, etanercept administration improved arthritis, corrected the erythrocyte indices and restored serum iron and ferritin with significant reduction in TNF-α, IL-6 and hepcidin gene expression. Hepcidin expression was negatively correlated to erythrocytic indices and iron profile, while it was positively correlated to serum TNF-α and IL-6 levels. CONCLUSION: Etanercept improved anemia in this animal model of RA, which could be explained in part by the reduction in hepcidin gene expression.


Assuntos
Anemia/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Hepcidinas/genética , Anemia/sangue , Anemia/etiologia , Animais , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Citocinas/sangue , Modelos Animais de Doenças , Ferritinas/sangue , Adjuvante de Freund , Hemoglobinas/análise , Masculino , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA