Functional iron status of chronic kidney disease patients at the University of Ilorin Teaching Hospital, Ilorin, Nigeria

Background: Functional iron deficiency has been found to be a common cause of poor response to erythropoiesis stimulating agents in anaemic patients with chronic kidney disease (CKD). Objectives: Assess the functional iron status of patients with chronic kidney disease. Methods: This was a hospital based cross sectional study. The study subjects were chronic kidney disease patients with age and sex matched healthy controls. Full blood count, serum ferritin, soluble transferring receptor, C-reactive protein, serum iron and total iron binding capacity were measured in the patients and healthy controls. Data was analyzed with statistical package for the social sciences software version 22.0. And the level of statistical significance was set at p. value < 0.05. Results: The mean ± SD of the age of patient with CKD was 55.0 + 15.4 years, while that of controls was 52.7 + 13.6 years. The mean serum ferritin, serum iron, TIBC and CRP were significantly higher in patients compared with controls (p<0.001, 0.023, <0.001 and 0.001) respectively. Functional iron deficiency was seen in 19.5% of patients with CKD. Conclusion: The predominant form of iron deficiency in our study was functional iron deficiency

Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)

The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)

New Oral Agent for Treatment of Anemia in Patient with Chronic Kidney Disease: Prolyl Hydroxylase Inhibitor / 대한내과학회지

Hypoxia inducible factor (HIF)-stabilizers are being developed for the renal anemia treatment. This small molecules inhibit prolyl hydroxylase domain (PHD)-containing enzymes, causing HIF activation instead of degradation under the state of normoxia, finally increase production of intrinsic erythropoiesis. Current treatment guidelines suggest that renal anemia should be treated mainly with iron and erythropoiesis stimulating agents (ESAs). But there are several complications and concerns such as hypertension, ESA refractory anemia and increased cardiovascular mortality in using ESAs. Advantages of HIF stabilizers over ESAs are orally available, no dose-up requirement for inflammation. So far new HIF stabilizers showed efficacy and safety in renal anemia treatment. This new therapeutic agent may emerge as a standard treatment option for renal anmia treatment.

Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Laboratory evidence for the hematopoietic potential of Beta vulgaris leaf and stalk extract in a phenylhydrazine model of anemia

This study was designed to provide laboratory evidence supporting the hematopoietic effect of Beta vulgaris (beet) leaf aqueous extract in phenylhydrazine-induced anemia model in albino rats. Extraction of the leaves/stalks was done by maceration in 30% hydro-ethanol for 48 h. An intraperitoneal injection of 20 mg/kg phenylhydrazine was applied for two consecutive days to develop hemolytic anemia on the 4th day after the 1st injection in 24 of 30 male albino rats. The animals were divided into 5 groups and received the following treatments: standard (ferrous ascorbate + folic acid; 13.5 + 0.135 mg/kg), B. vulgaris extract (100 and 200 mg/kg), or left untreated (normal and diseased controls). Blood samples were taken at 0, 4, 8, and 12 days of the experiment for hematological and clinico-chemical analysis. Beet leaf extract significantly restored the levels of red blood cells, white blood cells, hemoglobin, and hematocrit in dose- and time-dependent manners. Blood indices have been significantly corrected. Erythropoietin level was maintained at higher levels. Erythrocytic membrane oxidation biomarker (malondialdehyde) level was significantly reduced compared to the anemic untreated group. The extract exhibited potent, concentration (4-512 μg/mL)-dependent antioxidant activity indicated by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay, with IC50 value of 37.91 μg/mL. Beet leaf extract resulted in detection of flavonoid and phenolic compounds that may underlie its hematinic properties. These findings may indicate B. vulgaris as a good natural source for pharmaceutical preparations with hematopoietic effects and treatment of anemia and/or associated conditions.

The Prevalence and Management of Anemia in Chronic Kidney Disease Patients: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Anemia is a common and significant complication of chronic kidney disease (CKD). However, its prevalence and current management status has not been studied thoroughly in Korea. We examined the prevalence of anemia, its association with clinical and laboratory factors, and utilization of iron agents and erythropoiesis stimulating agents using the baseline data from the large-scale CKD cohort in Korea. We defined anemia when hemoglobin level was lower than 13.0 g/dL in males and 12.0 g/dL in females, or received by erythropoiesis stimulating agents. Overall prevalence of anemia was 45.0% among 2,198 non-dialysis CKD patients from stage 1 to 5. Diabetic nephropathy (DN) as a cause, CKD stages, body mass index (BMI), smoking, leukocyte count, serum albumin, iron markers, calcium, and phosphorus concentration were identified as independent risk factors for anemia. Considering the current coverage of Korean National Health Insurance System, only 7.9% among applicable patients were managed by intravenous iron agents, and 42.7% were managed by erythropoiesis stimulating agents.

Treatment of renal anemia: Erythropoiesis stimulating agents and beyond

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

The Global Developments in Transfusion Replacements and Patient Blood Management / 대한수혈학회지

Blood transfusions were once believed to the most potent and cost-effective method of improving patients' survival outcomes, but accumulating evidence over the past thirty years strongly suggests allogeneic transfusions as independent prognosticators of complications, prolonged hospital stay, and higher costs. A growing body of health care providers in Korea and throughout the world recognize a causal relationship between these adverse outcomes with liberal transfusion policies and call for a universal paradigm shift regarding the management of blood. Currently, the most promising contender is Patient Blood Management (PBM), which has been found to improve patient outcomes by conserving or optimizing the patient's own blood and physiologic reserves and advocating for restrictive transfusion policies. PBM incorporates evidence-based transfusion replacements to address anemia, bleeding, and blood disorders. These various methods–such as intravenous iron, erythropoiesis stimulating agents, coagulating factors, and topical hemostatic agents–are gaining recognition because of their ability to preclude the need for allogenic transfusions while effectively managing the patient's blood.

Recuento de células CD34+ en sangre periférica como predictor de adecuada recolección de progenitores hematopoyéticos para trasplante autólogo / Peripheral blood CD34+ cell count as a predictor of adequacy of hematopoietic stem cell collection for autologous transplantation / Contagem de células CD34+ em sangue periférico como preditor de adequada recolecção de progenitores hematopoiéticos para transplante autólogo

Introducción: para llevar a cabo un trasplante autólogo se deben movilizar los progenitores hematopoyéticos a la sangre periférica y posteriormente recolectarlos por aféresis. El recuento de células CD34+ es una herramienta para determinar el mejor momento para la recolección. Objetivo: evaluar la asociación entre el recuento de células CD34+ en sangre periférica y la recolección exitosa de progenitores hematopoyéticos. Materiales y métodos: evaluación de una prueba predictiva para determinar la utilidad del recuento de células CD34+ en sangre periférica como predictor del éxito de la recolección de progenitores hematopoyéticos en pacientes a los que se les va a hacer un trasplante autólogo. Resultados: se incluyó a 77 pacientes (mediana de edad: 49 años; rango: 5-66); el diagnóstico predominante fue linfoma (53,2 %). El porcentaje de pacientes con recolección exitosa de progenitores fue proporcional al número de células CD34+ en sangre periférica al finalizar la movilización. Proponemos que se deben tener más de 15 células CD34+/μL en sangre periférica para lograr una adecuada recolección de progenitores hematopoyéticos. Conclusión: el recuento de células CD34+ en sangre periférica es una herramienta útil para predecir la recolección exitosa de progenitores hematopoyéticos.

Introduction: In order to carry out an autologous transplantation, hematopoietic stem cells should be mobilized to peripheral blood and later collected by apheresis. The CD34+ cell count is a tool to establish the optimal time to begin the apheresis procedure. Objective: To evaluate the association between peripheral blood CD34+ cell count and the successful collection of hematopoietic stem cells. Materials and methods: A predictive test evaluation study was carried out to establish the usefulness of peripheral blood CD34+ cell count as a predictor of successful stem cell collection in patients that will receive an autologous transplantation. Results: 77 patients were included (median age: 49 years; range: 5-66). The predominant baseline diagnosis was lymphoma (53.2 %). The percentage of patients with successful harvest of hematopoietic stem cells was proportional to the number of CD34+ cells in peripheral blood at the end of the mobilization procedure. We propose that more than 15 CD34+ cells/μL must be present in order to achieve an adequate collection of hematopoietic stem cells. Conclusion: Peripheral blood CD34+ cell count is a useful tool to predict the successful collection of hematopoietic stem cells.

Introdução: para levar a cabo um transplante autólogo se devem mobilizar os progenitores hematopoiéticos ao sangue periférico e posteriormente os coletá-los por aféreses. A contagem de células CD34+ é uma ferramenta para determinar o melhor momento para a recolecção. Objetivo: avaliar a associação entre a contagem de células CD34+ em sangue periférico e a recolecção exitosa de progenitores hematopoiéticos. Materiais e métodos: avaliação de uma prova preditiva para determinar a utilidade da contagem de células CD34+ em sangue periférico como preditor do sucesso da recolecção de progenitores hematopoiéticos em pacientes aos que se lhes vá fazer um transplante autólogo. Resultados: se incluiu a 77 pacientes (média de idade: 49 anos; faixa: 5-66); o diagnóstico predominante foi linfoma (53,2 %). A porcentagem de pacientes com recolecção exitosa de progenitores foi proporcional ao número de células CD34+ em sangue periférico ao finalizar a mobilização. Propomos que se devem ter mais de 15 células CD34+/μL em sangue periférico para conseguir uma adequada recolecção de progenitores hematopoiéticos. Conclusão: A contagem de células CD34+ em sangue periférico é uma ferramenta útil para prever a recolecção exitosa de progenitores hematopoiéticos.

Anemia em pacientes submetidos à diálise peritoneal ambulatorial: prevalência e fatores associados / Anemia in patients undergoing ambulatory peritoneal dialysis: prevalence and associated factors

Resumo Introdução: A anemia é uma complicação frequente em pacientes em diálise e poucos estudos avaliaram sua ocorrência em pacientes submetidos à diálise peritoneal (DP). Objetivo: Este estudo teve como objetivo investigar a prevalência e fatores associados à presença de anemia em pacientes submetidos à DP de um único centro onde havia acesso irrestrito a agentes estimulantes da eritropoiese (AEE) e a suplementação de ferro intravenoso. Métodos: Estudo transversal que analisou variáveis demográficas, clínicas e laboratoriais de 120 pacientes. Anemia foi definida como hemoglobina (Hb) < 11g/dl. Resultados: Os pacientes estavam em DP por 17 meses, sendo 86% automatizada. A idade média foi de 58 ± 16,5 anos, 52% dos pacientes eram do sexo feminino e 29% diabéticos. Anemia esteve presente em 34 pacientes (28%). Quando comparados com pacientes sem anemia, aqueles com anemia recebiam maior dose de ferro (p = 0,02) e apresentavam menores triglicérides (p = 0,01). A Hb se correlacionou negativamente com as doses de ferro (r = -0,20;p = 0,03) e AEE (r = -0,23; p = 0,01), e positivamente com albumina (r = 0,38; p = 0,01), triglicérides (r = 0,24; p = 0,01) e índice de saturação da transferrina (r = 0,20; p = 0,03). Na análise múltipla, a concentração de albumina (coefβ = 0,84; 95% IC = 0,381,31;p < 0,001) e a dose de AEE (coefβ = -0,06; 95% IC = 0,00-0,00; p = 0,02) foram associadas de forma independente com a Hb. Conclusões: No presente estudo, anemia foi observada em aproximadamente 30% dos pacientes em programa de diálise peritoneal, com uso irrestrito de AEE e suplementação intravenosa de ferro. A saturação de transferrina e o estado nutricional, avaliado pela albumina, foram os fatores independentes associados à concentração de hemoglobina nesta população.

Abstract Introduction: Anemia is a common complication in dialysis patients, scare studies have evaluated anemia in patients undergoing peritoneal dialysis (PD). Objective: This study aimed to investigate the prevalence of anemia and its associated factors in patients undergoing PD in a single center where patients have free access to agents stimulating erythropoiesis (ESA) and intravenous iron supplementation. Methods: Cross-sectional study analyzing the demographic, clinical and laboratory variables of 120 patients. Anemia was defined as hemoglobin (Hb) < 11 g/dl. Results: Patients were on PD for 17 months, and the majority of them (86%) received automated PD. The mean age was 58 ± 16.5 years, and 52% were female and 29% were diabetes. Anemia was present in 34 (28%) patients. When compared with those without anemia, patients with anemia received a higher dose of iron (p = 0.02) and had a lower concentration of triglycerides (p = 0.01). Hb levels correlated negatively with iron (r = -0.20;p = 0.03) and ESA (r = -0.23; p = 0.01) doses and positively with albumin (r = 0.38; p = 0.01), triglycerides (r = 0.24; p = 0.01) and transferrin saturation (r = 0.20; p = 0.03). In multiple analyses, only the albumin concentration (beta = 0.84; 95% IC = 0.38-1.31;p < 0.001) and ESA dose (beta = -0.06; 95% IC = 0.00-0.00; p = 0.02) were independently associated with Hb levels. Conclusions: Almost 30% of PD patients had anemia, even with free access to erythropoietin and intravenous iron. The transferrin saturation and nutritional status assessed by albumin, were the factors associated with the occurrence of anemia in this population.

Erythropoiesis-stimulating Agents and Anemia in Patients with Non-dialytic Chronic Kidney Disease

Anemia is common in patients with advanced chronic kidney disease (CKD). Though erythropoiesis-stimulating agents (ESAs) have been strongly endorsed in guidelines, it is of particular financial interest. Recently, the reimbursement of ESAs in non-dialytic patients was started by the Korean National Health Insurance System. Thus, we investigated the impact of the reimbursement of ESAs on the anemia care in non-dialytic CKD patients. Medical records of patients with advanced CKD (estimated GFR <30 mL/min/1.73 m2) were reviewed. Use of ESAs, blood transfusion, and hemoglobin concentrations were analyzed from one year prior to reimbursement to three years following. We used multivariable modified Poisson regression to estimate the utilization prevalence ratio (PRs). A total of 1,791 medical records were analyzed. The proportion of patients receiving ESAs increased from 14.8% before reimbursement to a peak 33.6% in 1 yr after reimbursement; thereafter, ESA use decreased to 22.4% in 3 yr after reimbursement (compared with baseline; PR, 2.19 [95% CI, 1.40-3.42]). In patients with Hb <10 g/dL, the proportion of receiving ESAs increased from 32.1% before reimbursement to 66.7% in 3 yr after reimbursement (compared with baseline; PR, 2.04 [95% CI, 1.25-3.32]). Mean hemoglobin concentrations were 10.06±1.54 g/dL before reimbursement and increased to 10.78±1.51 g/dL in 3 yr after the reimbursement change (P=0.001). However, the requirement of blood transfusion was not changed over time. With the reimbursement of ESAs, the advanced CKD patients were more likely to be treated with ESAs, and the hemoglobin concentrations increased.

Expressão da enzima indoleamina-2, 3-dioxigenase em truta arco-íris (Oncorhynchus mykiss) / Expression of the enzyme indoleamine-2, 3-dioxygenase in Rainbow Trout (Oncorhynchus mykiss

A indoleamina 2,3-dioxigenase (IDO) é uma enzima que cataboliza o aminoácido triptofano, levando à inibição da proliferação de linfócitos T, seja pela exaustão desse aminoácido no ambiente, ou pela indução via catabólitos induzindo-os a apoptose. Em mamíferos, esta enzima atua em diversas condições do organismo como a gestação, infecções, inflamações crônicas, transplantes e tumores, atuando na regulação imunológica. Estudos recentes identificaram a presença de moléculas homólogas a IDO em espécies filogeneticamente inferiores, cuja função parece estar restrita ao metabolismo do triptofano como fonte de energia. Este estudo teve por objetivo averiguar a expressão da IDO em células sanguíneas e órgãos hematopoiéticos de truta arco-íris pela imuno-histoquímica, buscando evidências de que a mesma poderia, nesta espécie, estar relacionada ao sistema imune. A expressão de IDO foi observada nos órgãos hematopoiéticos estudados incluindo o rim cefálico que apresentou marcação em células interrenais e leucócitos; baço, na qual a marcação restringiu à alguns leucócitos; no fígado a marcação ficou limitada à apenas algumas células dentro dos vasos sanguíneos e nas extensões sanguíneas pode-se visualizar a marcação de alguns leucócitos como os monócitos, linfócitos e neutrófilos. A predominância da marcação da IDO nesses tecidos pode constituir uma evidência de que a IDO identificada na O. mykiss esteja relacionada ao sistema imunológico nessa espécie...

Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catabolizes the amino acid tryptophan, leading to inhibition of T lymphocyte proliferation, whether by depletion of this amino acid in the environment, or by induction via the catabolites inducing apoptosis. In mammals, this enzyme acts on various conditions of the body such as pregnancy, infections, chronic inflammation, transplantation and tumors, acting in immune regulation. Recent studies have identified the presence of homologous molecules IDO lower phylogenetically related species, whose function appears to be confined to the tryptophan metabolism as an energy source. This study aimed to investigate the expression of IDO in blood cells and hematopoietic organs of rainbow trout by immunohistochemistry, seeking evidence that it could, this species is related to the immune system. The expression of IDO was observed in hematopoietic organs studied including head kidney that show labeling in interrenal cells and leukocytes; spleen, in which the marking restricted to a few leukocytes in the liver;, labeling was restricted to only certain cells within the blood vessels and the blood extensions can view the marking of some leukocytes including monocytes, lymphocytes and neutrophils. The predominance of IDO marking these tissues may constitute evidence that IDO identified in O. mykiss is related to the immune system in this species...

Idiopathic erythrocytosis in a patient on chronic hemodialysis

A 78-year-old man on hemodialysis presented to our hospital with erythrocytosis. He had started hemodialysis 4 years previously, with a hemoglobin level of 9.8 g/dL, and was administered erythropoiesis stimulating agents and ferrous sulfate. Two years previously, his hemoglobin level increased to 14.5 g/dL and the treatment for anemia was discontinued. He continued hemodialysis thrice weekly; however, the hemoglobin level had increased to 17.0 g/dL at the time of presenting to our hospital. His serum erythropoietin level was 31.4 mIU/mL (range, 3.7-31.5 mIU/mL), carboxyhemoglobin level was 0.6% (range, 0-1.5%), and oxygen saturation in ambient air was 95.4%. The JAK2 V617F mutation was not observed and other bone marrow abnormalities were not identified. The patient was diagnosed with bladder cancer and a transurethral resection was performed. Eight months after the treatment of bladder cancer, his hemoglobin level was 15.1 g/dL, and he was diagnosed with idiopathic erythrocytosis.

Uso de medicamentos no primeiro trimestre de gravidez: avaliação da segurança dos medicamentos e uso de ácido fólico e sulfato ferroso / Medication use during the first trimester of pregnancy: drug safety and adoption of folic acid and ferrous sulphate

OBJETIVO: Identificar o perfil de uso de medicamentos no primeiro trimestre de gravidez com ênfase na avaliação da segurança e na adoção do ácido fólico e do sulfato ferroso por gestantes em uma Unidade Básica de Saúde da região Sul do Brasil. MÉTODOS: Trata-se de estudo transversal aninhado a uma coorte de gestantes. Os medicamentos foram classificados segundo a Anatomical Therapeutic Chemical (ATC), e a segurança avaliada segundo a Food and Drug Administration (FDA) e a Agência Nacional de Vigilância Sanitária (ANVISA). Foi investigado o uso/prescrição de sulfato ferroso e ácido fólico segundo o protocolo do Ministério da Saúde. RESULTADOS: Foram incluídas 212 gestantes. Dessas, 46,7% estavam em uso de medicamentos no momento do diagnóstico da gravidez e 97,6% utilizaram medicamentos no primeiro trimestre gestacional. O percentual mais elevado de automedicação ocorreu antes do início do pré-natal (64,9%). Observou-se maior exposição a medicamentos de risco D e X, segundo a classificação do FDA, antes do início do pré-natal (23,0%). Entre as gestantes, 32,5% não seguiam o protocolo de uso de ácido fólico e sulfato ferroso do Ministério da Saúde. No total, 67,9% das gestantes tiveram exposição inadequada aos medicamentos. Houve diferença entre as proporções de medicamentos utilizados segundo a ATC, e os principais grupos anatômicos identificados foram os dos medicamentos que atuam no sangue e órgãos hematopoiéticos e anti-infecciosos de uso sistêmico. Na época do diagnóstico da gravidez, observou-se expressivo uso de medicamentos que atuam no sistema geniturinário e hormônios sexuais (16,2%), como anticoncepcionais orais, o que provavelmente está relacionado ao percentual ...

PURPOSE: To identify the profile of use of medication during the first trimester of pregnancy with emphasis on safety assessment and on the adoption of folic acid and ferrous sulfate by pregnant women attended at a Basic Health Unit in Brazil. METHODS: This was a cross-sectional study nested in a cohort of pregnant women. Medications were classified according to the Anatomical Therapeutic Chemical (ATC), and their safety was evaluated according to the Food and Drug Administration (FDA) and the Brazilian Health Surveillance Agency (ANVISA). The adoption of ferrous sulfate and folic acid was investigated according to the protocol set forth by the Brazilian Ministry of Health. RESULTS: The survey included 212 pregnant women, 46.7% of whom were taking medications at the time of pregnancy diagnosis, and 97.6% used medication during the first trimester after diagnosis. The highest percentage of self-medication occurred before the beginning of prenatal care (64.9%). According to the FDA criteria, there was a high level of exposure to D and X risk drugs before the beginning of prenatal care (23.0%), which was also observed for drugs not recommended by ANVISA (36.5%). Of the surveyed sample, 32.5% did not follow the protocol of the Brazilian Ministry of Health. In all, 67.9% of pregnant women had inadequate drug exposure. There was a difference between the proportions of drugs used according to the ATC, and the main anatomical groups identified were the drugs that act on blood and blood-forming organs, and anti-infective medications for systemic use. When pregnancy was diagnosed, the use of a large number of medications that act on the genitourinary system and sex hormones (16.2%) was identified, such as oral contraceptives, a fact probably related to the percentage of unplanned pregnancies (67.0%), on the same occasion 4 pregnant women used folic acid and 3 used ferrous sulphate. CONCLUSION: The present results show that a large number ...

Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.

Effect of anemia correction on left ventricular structure and filling pressure in anemic patients without overt heart disease

BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. RESULTS: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.