RESUMEN
Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the ß-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other ß-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country.
Asunto(s)
Anemia de Células Falciformes , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/tratamiento farmacológico , Humanos , Brasil/epidemiología , Manejo de la Enfermedad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Mutación , Hemoglobina Falciforme/genéticaRESUMEN
Sickle cell disease (SCD) is a group of hereditary chronic diseases with a substantial impact on quality of life and morbimortality. In Brazil, it is 1 of the most common hereditary diseases; however, there are sparse epidemiological data for the country. Using data from death certificates, we aimed to estimate the median age at death, years of life lost because of SCD, and the median survival. From 2015 to 2019, we identified 3320 records of deaths of individuals with SCD, from a total of 6 553 132 death records. Among individuals with SCD, the median age at death was 37 years less than that of the general population (SCD: aged 32.0 years at death, interquartile range [IQR], 19.0-46.0; general population: aged 69.0 years at death; IQR, 53.0-81.0). Results were consistent when stratified by sex or race. Over the 5 years evaluated, crude death rates varied from 0.30 to 0.34 per 100 000 inhabitants (mean 0.32 per 100 000 inhabitants). We estimated a prevalence of 60 017 individuals living with SCD (29.02 cases per 100 000) and an average incidence of 1362 cases yearly. The median estimated survival was 40 years for individuals with SCD and 80 years for the general population. SCD was associated with an increased risk of mortality in most age ranges. Among individuals with SCD aged between 1 and 9 years and between 10 and 39 years, the risk of death was 32 and 13 times higher, respectively. The most common causes of death were sepsis and respiratory failure. These results highlight the burden of SCD in Brazil and the necessity of improved care for this population.
Asunto(s)
Anemia de Células Falciformes , Calidad de Vida , Humanos , Lactante , Preescolar , Niño , Brasil/epidemiología , Anemia de Células Falciformes/complicaciones , Incidencia , PrevalenciaRESUMEN
BACKGROUND: Sickle cell disease (SCD) may cause several impacts to patients and the whole society. About 4% of the population has the sickle cell trait in Brazil, and 60,000 to 100,000 have SCD. However, despite recognizing the significant burden of disease, little is known about SCD costs. OBJECTIVE: To estimate SCD societal costs based on disease burden modelling, under Brazilian societal perspective. METHODS: A disease burden model was built considering the societal perspective and a one-year time horizon, including direct medical and indirect costs (morbidity and mortality). The sum of life lost and disability years was considered to estimate disability-adjusted life years (DALYs). Data from a public database (DATASUS) and the prevalence obtained from literature or medical experts were used to define complications prevalence and duration. Costs were defined using data from the Brazilian public healthcare system table of procedures and medications (SIGTAP) and the human capital method. RESULTS: Annual SCD cost was 413,639,180 USD. Indirect cost accounted for the majority of burden (70.1% of the total; 290,158,365 USD vs 123,480,816 USD). Standard of care and chronic complications were the main source of direct costs among adults, while acute conditions were the main source among children. Vaso-occlusive crisis represented the complication with the highest total cost per year in both populations, 11,400,410 USD among adults and 11,510,960 USD among children. CONCLUSIONS: SCD management may impose an important economic burden on Brazilian society that may reach more than 400 million USD per year.
Asunto(s)
Anemia de Células Falciformes , Costos de la Atención en Salud , Adulto , Anemia de Células Falciformes/epidemiología , Brasil/epidemiología , Niño , Costo de Enfermedad , Estrés Financiero , HumanosRESUMEN
Sickle cell disease is characterized by vaso-occlusive phenomena and haemolytic anaemia. There is a significant concern that the overlap of COVID-19 lung disease with acute chest syndrome that occurs in sickle cell patients may result in serious complications. Case reports of sickle cell patients with COVID-19 have been published. Here, we present a case series of COVID-19 infection in sickle cell patients in a developing country (Brazil). Only 10 patients tested positive so far for SARS-CoV-2 of 600 patients followed at our institution, of which 8 needed hospitalization (one in the intensive care unit), with no deaths. Even in a middle-income country, COVID-19 was reported to be relatively mild in sickle cell patients. In relation to risk factors, blood type O seems to confer some protection against developing severe COVID-19, a finding that could guide clinicians to adopt more clinical surveillance for patients with non-O blood type in sickle cell patients.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/sangre , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/terapia , COVID-19/sangre , COVID-19/terapia , SARS-CoV-2/metabolismo , Adulto , Anemia de Células Falciformes/epidemiología , Brasil , COVID-19/epidemiología , Niño , Países en Desarrollo , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To date, blood banks apply routine diagnosis to a specific spectrum of transfusion-transmitted viruses. Even though this measure is considered highly efficient to control their transmission, the threat imposed by emerging viruses is increasing globally, which can impact transfusion safety, especially in the light of the accelerated viral discovery by novel sequencing technologies. One of the most important groups of patients, who may indicate the presence of emerging viruses in the field of blood transfusion, is the group of individuals who receive multiple transfusions due to hereditary hemoglobinopathies. It is possible that they harbor unknown or unsuspected parenterally-transmitted viruses. In order to elucidate this, nucleic acids from 30 patients with beta-thalassemia were analyzed by Illumina next-generation sequencing and bioinformatics analysis. Three major viral families: Anelloviridae, Flaviviridae and Hepadnaviridae were identified. Among them, anelloviruses were the most representative, being detected with high number of reads in all tested samples. Human Pegivirus 1 (HPgV-1, or GBV-C), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) were also identified. HBV and HCV detection was expected due to the high seroprevalence in patients with beta thalassemia. Our results do not confirm the presence of emerging or unsuspected viruses threatening the transfusion safety at present, but can be used to actively search for viruses that threaten blood transfusion safety. We believe that the application of viral metagenomics in multiple-transfused patients is highly useful to monitor possible viral transfusion threats and for the annotation of their virome composition.
Asunto(s)
Talasemia beta , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metagenómica , Estudios Seroepidemiológicos , Viroma , Talasemia beta/genéticaRESUMEN
Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. The virus is acquired by fecal-oral route; however, it can also be transmitted by blood transfusion. The objective of the study was to examine anti-HEV immunoglobulin G and HEV RNA prevalence in multiple transfused patients with thalassemia and sickle cell disease (SCD), and in blood donors. The HEV seroprevalence in the patients was 13% (20% in thalassemics; 7.7% in SCD), and 11% in blood donors. No positive result for HEV RNA was obtained. This is a pioneer study examining HEV circulation in Brazilian patients with hemoglobinopathies.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Virus de la Hepatitis E , Hepatitis E/epidemiología , Hepatitis E/etiología , Talasemia/complicaciones , Anemia de Células Falciformes/terapia , Transfusión Sanguínea , Brasil/epidemiología , Femenino , Virus de la Hepatitis E/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Prevalencia , Vigilancia en Salud Pública , ARN Viral , Estudios Seroepidemiológicos , Talasemia/terapiaRESUMEN
Hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. The virus is acquired by fecal-oral route; however, it can also be transmitted by blood transfusion. The objective of the study was to examine anti-HEV immunoglobulin G and HEV RNA prevalence in multiple transfused patients with thalassemia and sickle cell disease (SCD), and in blood donors. The HEV seroprevalence in the patients was 13% (20% in thalassemics; 7.7% in SCD), and 11% in blood donors. No positive result for HEV RNA was obtained. This is a pioneer study examining HEV circulation in Brazilian patients with hemoglobinopathies.
RESUMEN
The thalassemia syndromes (α- and ß-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or ß-globin chain production results in impaired red blood cell synthesis, anemia, and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis, and dysfunctional iron metabolism has not been investigated in both α-thalassemia carriers (ATC) and ß-thalassemia carriers (BTC). Here, we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changes in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferritin and (hepcidin/ferritin)/sTfR are, respectively, increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis.
Asunto(s)
Eritropoyesis/genética , Heterocigoto , Hierro/metabolismo , Talasemia/genética , Talasemia/metabolismo , Donantes de Sangre , Índices de Eritrocitos , Ferritinas/sangre , Ferritinas/metabolismo , Hepcidinas/sangre , Hepcidinas/metabolismo , Humanos , Hierro/sangre , Mutación , Talasemia/sangre , Globinas alfa/genética , Globinas beta/genéticaRESUMEN
The role of the human cytomegalovirus (HCMV) infection in individuals with hemoglobinopathies is unclear. Our objective was to examine the molecular and genotypic characteristics of HCMV in patients with sickle cell disease, beta-thalassemia major, and volunteer blood donors by viral load quantitation, glycoprotein B (gB) genotyping, and phylogenetic analysis. The patients with sickle cell disease demonstrated the highest HCMV DNA prevalence (13.8%), followed by the patients with beta-thalassemia major (7.6%), and the blood donors (3%). The infection was characterized by a low mean viral load (3.8×10(3) copies/mL), but infections with higher copy numbers were also observed. Genotype gB2 was detected in the majority of cases (90.9%), followed by genotype gB1 (9.1%). No gB3/gB4 genotype was detected. No statistical significance was observed between HCMV DNAemia/gB genotype and hematological alterations or severity of the disease. The high number of sickle cell disease patients with HCMV DNAemia could be due to their partial immune dysfunction (multiple transfusions, spleen dysfunction, hydroxyurea treatment). The extensive HCMV gB2 prevalence in patients with hemoglobinopathies is probably due to HCMV epidemiologic characteristics in the examined region, and can be important during the clinical management of these patients.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Infecciones por Citomegalovirus/virología , Citomegalovirus/clasificación , Variación Genética , Proteínas del Envoltorio Viral/genética , Talasemia beta/complicaciones , Adolescente , Adulto , Anciano , Brasil , Niño , Preescolar , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Femenino , Genotipo , Técnicas de Genotipaje , Humanos , Lactante , Masculino , Persona de Mediana Edad , Filogenia , Carga Viral , Adulto JovenRESUMEN
Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 10(6)/ml vs. 67.45 × 10(6)/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10(6)/ml vs. 26.31 × 10(6)/ml; p = 0.05), monocytes (51.31 × 10(6)/ml vs. 9.03 × 10(6)/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10(6)/ml vs. 0.27 × 10(6)/ml; p = 0.0058), endothelium (49.42 × 10(6)/ml vs. 7.23 × 10(6)/ml; p = 0.007) and endothelium with TF (1.42 × 10(6)/ml vs. 0.26 × 10(6)/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.
Asunto(s)
Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/administración & dosificación , Micropartículas Derivadas de Células/metabolismo , Fibrinólisis/efectos de los fármacos , Hidroxiurea/administración & dosificación , Adulto , Anemia de Células Falciformes/patología , Animales , Antitrombinas/sangre , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Megaloblastos/metabolismo , Megaloblastos/patología , Monocitos/metabolismo , Monocitos/patología , Tromboplastina/biosíntesisRESUMEN
Although xenotropic murine leukemia virus-related virus (XMRV) has been regarded as a laboratory contaminant, it remains one of the most controversial viruses. The objective of the study was to determine if XMRV is present in 44 patients with beta-thalassemia major, 48 with sickle cell disease, and 89 volunteer blood donors. After RNA/ DNA extraction from plasma/buffy coat the samples were screened for XMRV sequences by conserved nested GAG primers. None of the RNA samples showed a positive result. Surprisingly, four DNA samples obtained from blood donors were positive for XMRV provirus. The subsequent phylogenetic analysis revealed that these sequences are identical to the positive control (murine leukemia retrovirus) and are probably consistent with laboratory contamination. XMRV infection (provirus and viral RNA) was absent in multiply transfused patients and volunteer blood donors. The positive result obtained from some blood donors probably reflects laboratory contamination. We believe that XMRV does not pose risk to blood transfusion.
Asunto(s)
Anemia de Células Falciformes/virología , Infecciones por Retroviridae/virología , Virus Relacionado con el Virus Xenotrópico de la Leucemia Murina/aislamiento & purificación , Talasemia beta/virología , Adolescente , Adulto , Animales , Donantes de Sangre , Transfusión Sanguínea , Brasil , Niño , Preescolar , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Virus Relacionado con el Virus Xenotrópico de la Leucemia Murina/clasificación , Virus Relacionado con el Virus Xenotrópico de la Leucemia Murina/genética , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012). METHODS: The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9±5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. RESULTS: A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8±2.63 weeks, and mean newborn weight was 2.809±643.8g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternal-fetal complications during pregnancy was evaluated. CONCLUSIONS: Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal) in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease.
RESUMEN
Objective: The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012). Methods: The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9 ± 5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. Results: A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8 ± 2.63 weeks, and mean newborn weight was 2.809 ± 643.8 g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternalfetal complications during pregnancy was evaluated. Conclusions: Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal) in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease...
Asunto(s)
Humanos , Anemia de Células Falciformes , Transfusión Sanguínea , Embarazo , Complicaciones del EmbarazoRESUMEN
CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies.
Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Adolescente , Adulto , Análisis de Varianza , Anemia de Células Falciformes/sangre , Antidrepanocíticos/farmacología , Transfusión Sanguínea , Brasil , Niño , Índices de Eritrocitos/efectos de los fármacos , Femenino , Hemoglobina Fetal/efectos de los fármacos , Hemoglobina Falciforme/efectos de los fármacos , Humanos , Hidroxiurea/farmacología , Masculino , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.
Asunto(s)
Niño , Preescolar , Femenino , Humanos , Masculino , Anemia de Células Falciformes/virología , Infecciones por Parvoviridae/virología , /genética , Enfermedad Aguda , Anemia de Células Falciformes/complicaciones , Anticuerpos Antivirales/sangre , ADN Viral/análisis , Genotipo , Filogenia , Infecciones por Parvoviridae/complicaciones , Carga ViralRESUMEN
Human parvovirus B19 is a well-known cause of severe conditions in patients with sickle cell disease, but the molecular mechanisms of the infection are insufficiently understood. The different clinical outcome of the acute parvovirus B19 infection in two pediatric patients with sickle cell disease has been examined. One of them developed life-threatening condition requiring emergency transfusions, while the other had asymptomatic infection, diagnosed occasionally. Both cases had high viral load and identical subgenotype, indicating that the viral molecular characteristics play a minimal role in the infection outcome.
Asunto(s)
Anemia de Células Falciformes/virología , Infecciones por Parvoviridae/virología , Parvovirus B19 Humano/genética , Enfermedad Aguda , Anemia de Células Falciformes/complicaciones , Anticuerpos Antivirales/sangre , Niño , Preescolar , ADN Viral/análisis , Femenino , Genotipo , Humanos , Masculino , Infecciones por Parvoviridae/complicaciones , Filogenia , Carga ViralRESUMEN
CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies. .
CONTEXTO E OBJETIVO A doença falciforme (SCD) é o distúrbio genético mais comum entre afrodes-cendentes, afetando aproximadamente 3.500 recém-nascidos a cada ano no Brasil. A hidroxiureia (HU) é a única droga efetiva para o tratamento dos pacientes com SCD, reduzindo a morbidade e a mortalidade da doença. O objetivo do estudo foi analisar os efeitos da HU em pacientes com SCD em nossa instituição. TIPO DE ESTUDO E LOCAL Estudo retrospectivo realizado em um centro de anemia falciforme em Ribeirão Preto, São Paulo, Brasil. MÉTODOS Nós analisamos os dados clínicos e laboratoriais de 37 pacientes. Os parâmetros hematológicos e eventos clínicos que ocorreram no ano anterior e durante o primeiro ano de tratamento com HU foram analisados. A dose média de HU foi 24.5 ± 5.5 mg/kg/dia. RESULTADOS Houve aumento em três parâmetros estudados: hemoglobina (8,3 g/dl para 9,0 g/dl, P = 0,0003), hemoglobina fetal (HbF) (2,6% para 19,8%, P < 0,0001) e volume corpuscular médio (VCM) (89 para 105 fl, P = 0,001); e redução do número de leucócitos (10.050/µl para 5.700/µl, P < 0,0001), neutrófilos (6.200/µl para 3.400/µl, P = 0,001), plaquetas (459.000/µl para 373.000/µl, P = 0,0002), crises dolorosas (1,86 para 0,81, P = 0,0014), síndrome torácica aguda (0,35 para 0,08, P = 0,0045), infecções (1,03 para 0,5, P = 0,047), hospitalizações (1,63 para 0,53, P = 0,0013) e número de transfusões (1,23 para 0,1, P = 0,0051). CONCLUSÃO Os pacientes apresentaram melhora clínica e hematológica, com aumento da HbF e redução da taxa de infecção, dado este não explorado na maioria dos estudos clínicos já publicados. .
Asunto(s)
Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Análisis de Varianza , Anemia de Células Falciformes/sangre , Antidrepanocíticos/farmacología , Transfusión Sanguínea , Brasil , Índices de Eritrocitos/efectos de los fármacos , Hemoglobina Fetal/efectos de los fármacos , Hemoglobina Falciforme/efectos de los fármacos , Hidroxiurea/farmacología , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
4-nerolidylcatechol (4-NC) is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl) on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast), however 4-NC was more cytotoxic (IC50 = 31.4 µM) and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at -20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at -20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds.
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Antimaláricos/farmacología , Antioxidantes/farmacología , Catecoles/química , Catecoles/farmacología , Piper/química , Células 3T3-L1 , Animales , Antimaláricos/química , Antioxidantes/química , Hidroxianisol Butilado/química , Hidroxianisol Butilado/farmacología , Hidroxitolueno Butilado/química , Hidroxitolueno Butilado/farmacología , Supervivencia Celular/efectos de los fármacos , Concentración 50 Inhibidora , Malaria/tratamiento farmacológico , Ratones , Dinámicas no Lineales , Raíces de Plantas/química , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/crecimiento & desarrolloRESUMEN
Human Parvovirus B19 (B19V) is a recognized cause of life-threatening conditions among patients with hemoglobinopathies. This study investigates B19V infection in patients with sickle cell disease and ß-thalassemia using different experimental approaches. A total of 183 individuals (144 with sickle cell disease and 39 with ß-thalassemia major) and 100 healthy blood donors were examined for B19V using anti-B19V IgG enzyme immunoassay, quantitative PCR, DNA sequencing, and phylogenetic analysis. Viremia was documented in 18.6% of patients and 1% of donors, and was generally characterized by low viral load (VL); however, acute infections were also observed. Anti-B19V IgG was detected in 65.9% of patients with sickle cell disease and in 60% of donors, whereas the patients with thalassemia exhibited relatively low seroreactivity. The seroprevalence varied among the different age groups. In patients, it progressively increased with age, whereas in donors it reached a plateau. Based on partial NS1 fragments, all isolates detected were classified as subgenotype 1A with a tendency to elicit genetically complex infections. Interestingly, quasispecies occurred in the plasma of not only patients but also donors with even higher heterogeneity. The partial NS1 sequence examined did not exhibit positive selection. Quantitation of B19V with a conservative probe is a technically and practically useful approach. The extensive spread of B19V subgenotype 1A in patients and donors and its recent introduction into the countryside of the São Paulo State, Brazil were demonstrated; however, it is difficult to establish a relationship between viral sequences and the clinical outcomes of the infection.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Donantes de Sangre , Infecciones por Parvoviridae/epidemiología , Infecciones por Parvoviridae/virología , Parvovirus B19 Humano/clasificación , Parvovirus B19 Humano/genética , Talasemia beta/complicaciones , Adolescente , Adulto , Factores de Edad , Anciano , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Niño , Preescolar , Análisis por Conglomerados , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Humanos , Inmunoglobulina G/sangre , Lactante , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Parvovirus B19 Humano/aislamiento & purificación , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Estudios Seroepidemiológicos , Proteínas no Estructurales Virales/genética , Adulto JovenRESUMEN
Human parvovirus B19 (B19V) infection can be a life-threatening condition among patients with hereditary (chronic) hemolytic anemias. Our objective was to characterize the infection molecularly among patients with sickle cell disease and thalassemia. Forty-seven patients (37 with sickle cell disease, and 10 with ß-thalassemia major) as well as 47 healthy blood donors were examined for B19V infection by anti-B19V IgG enzyme immunoassay, quantitative PCR, which detects all B19V genotypes, and DNA sequencing. B19V viremia was documented in nine patients (19.1%) as two displayed acute infection and the rest had a low titre viremia (mean 3.4 × 10(4) copies/mL). All donors were negative for B19V DNA. Anti-B19V IgG was detected in 55.3% of the patients and 57.4% among the donors. Based on partial NS1 fragments, all patient isolates were classified as genotype 1 and subgenotype 1A. The evolutionary events of the examined partial NS1 gene sequence were associated with a lack of positive selection. The quantification of all B19V genotypes by a single hydrolytic probe is a technically useful method, but it is difficult to establish relationships between B19V sequence characteristics and infection outcome.