RESUMEN

BACKGROUND: Cardiovascular diseases in aging people with hemophilia (PWH) represent a growing concern. The underlying hypocoagulability probably provides a protective effect against acute thrombus formation, but the limited data available show no preventive effect against the development of atherogenesis in PWH. Atherosclerosis-prone mice are attractive tools for the study of atherosclerosis development, and may provide insights into disease progression in PWH. METHODS: Severe hemophilia A (factor VIII-deficient [FVIII(o)]) mice were crossed with mice lacking apolipoprotein E (ApoE(-/-)) or mice lacking the LDL receptor (LDLR(-/-)), and then compared to hemostatically normal littermate controls. After mice had received atherogenic diets for 8, 22 or 37 weeks, atherosclerotic lesion size and phenotypic characterization were analyzed in the aortic sinus and whole aortas. RESULTS: ApoE(-/-)/FVIII(o) mice showed a time-dependent protective effect against the development of atherosclerosis, beginning after 22 diet-weeks and persisting to 37 diet-weeks in both the aorta sinus and whole aorta as compared with ApoE(-/-) mice. Notably, the FVIII deficiency did not influence the progression of atherosclerosis in the FVIII(o)/LDLR(-/-) model as compared with controls at early or late time points. CONCLUSIONS: Hypocoagulability ameliorates vascular disease in the ApoE-deficient model in a lipid-independent manner. Interestingly, FVIII deficiency did not affect the development of atherosclerosis in LDLR(-/-) mice. In contrast to the ApoE model, the LDLR model resembles the lipid profile that is commonly observed in humans with atherosclerosis. These findings, to a certain extent, support the notion of atherosclerosis development in the complete absence of FVIII.

Asunto(s)

Aterosclerosis/etiología , Coagulación Sanguínea , Hemofilia A/complicaciones , Animales , Aorta/patología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/sangre , Aterosclerosis/genética , Aterosclerosis/patología , Coagulación Sanguínea/genética , Colesterol/sangre , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Factor VIII/genética , Factor VIII/metabolismo , Genotipo , Hemofilia A/sangre , Hemofilia A/genética , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Receptores de LDL/deficiencia , Receptores de LDL/genética , Factores de Tiempo

RESUMEN

The presence of bees (Apis mellifera L.) in urban areas has increased in recent years due to environmental disturbances caused by humans. Bee migration to cities may provoke serious accidents, since some people present allergic reactions to their venoms. In Rio Claro city, São Paulo state, Brazil, the number of calls to the fire brigade for removal of bee swarms, and the number admissions in local hospitals due to bee stings were investigated during 2002 and 2003, and a correlation between these data and the average temperature, rainfall and relative humidity was found. The study period was divided into three phases according to the number of times that the fire brigade was called to remove swarms (263 times): January to July 2002 - 51 calls (19.39 percent); August 2002 to July 2003 - 140 calls (53.23 percent); and August to December 2003 - 72 calls (27.38 percent). A significant correlation among the number of calls, the local temperature and rainfall was detected. The number of accidents was not associated with environmental variables. Based on the current results, public activities for prevention of bee attacks may be developed to avoid unwanted contact between humans and these insects, and/or provide the appropriate management of the colonies.

Asunto(s)

Animales , Abejas , Humedad , Mordeduras y Picaduras de Insectos/prevención & control , Temperatura , Área Urbana , Migración Animal

RESUMEN

The presence of bees (Apis mellifera L.) in urban areas has increased in recent years due to environmental disturbances caused by humans. Bee migration to cities may provoke serious accidents, since some people present allergic reactions to their venoms. In Rio Claro city, São Paulo state, Brazil, the number of calls to the fire brigade for removal of bee swarms, and the number admissions in local hospitals due to bee stings were investigated during 2002 and 2003, and a correlation between these data and the average temperature, rainfall and relative humidity was found. The study period was divided into three phases according to the number of times that the fire brigade was called to remove swarms (263 times): January to July 2002 51 calls (19.39%); August 2002 to July 2003 140 calls (53.23%); and August to December 2003 72 calls (27.38%). A significant correlation among the number of calls, the local temperature and rainfall was detected. The number of accidents was not associated with environmental variables. Based on the current results, public activities for prevention of bee attacks may be developed to avoid unwanted contact between humans and these insects, and/or provide the appropriate management of the colonies.(AU)

Asunto(s)

26016/clasificación , Clima , Mordeduras y Picaduras/complicaciones , Hipersensibilidad

RESUMEN

The effects of the administration of Carapa guianensis Aublet (Meliaceae) seed oil were investigated during pregnancy in female Wistar rats. Five groups of pregnant rats (n=5-9 per group) were treated orally from the 7th to the 14th day of pregnancy (organogenic period), at doses of: 0, 0.375, 0.75, 1.5 and 3.0gkg(-1). On the 20th day of pregnancy, the animals were sacrificed and laparotomized to evaluate reproductive parameters. The results showed that there was no difference between the control and treated groups in terms of the number of live and dead fetuses, the dam-offspring relationship, the weight of the fetus, the weight of the placentae and ovaries, the number of implantation sites, the number of resorption sites, the number of corpora lutea in the ovaries, and the pre- and post-implantation loss rates. It is therefore concluded that administration of Carapa guianensis seed oil did not bring about any toxic effect on pregnancy in Wistar rats.

Asunto(s)

Meliaceae , Aceites de Plantas/toxicidad , Preñez/efectos de los fármacos , Embarazo/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Femenino , Resultado del Embarazo , Ratas , Ratas Wistar , Semillas

RESUMEN

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber disease is a systemic fibrovascular dysplasia with an autosomal dominant inheritance pattern. Mutations in two genes, endoglin and ALK-1, are known to cause HHT, both of which mediate signaling by transforming growth factor beta ligands in vascular endothelial cells. Ten patients were analyzed. Diagnosis of HHT was carried out by means of family history, recurrent bleeding, and the presence of multiple telangiectases lesions. Conformation-sensitive gel electrophoresis analyses with consistent abnormal migration patterns were cloned and sequenced using the MegaBace 1000 DNA automated analyzer. Three novel mutations were identified in the coding sequence of the ALK-1 gene in five patients and their families, which demonstrated clinical manifestations of HHT type 2. These mutations included a G insertion and a T deletion of single base pairs in exons 3 and 7, as well as missense mutations in exons 7 and 8 of the ALK-1 gene. These data indicate that loss-of-function mutations in a single allele of the ALK1 locus are sufficient to contribute to defects in maintaining endothelial integrity. We suggest the high rate of mutation detection and the small size of the ALK-1 gene make genomic sequencing a viable diagnostic test for HHT2.

Asunto(s)

Receptores de Activinas Tipo II/genética , Mutación/genética , Telangiectasia Hemorrágica Hereditaria/enzimología , Telangiectasia Hemorrágica Hereditaria/genética , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Análisis Mutacional de ADN , Exones/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje

RESUMEN

OBJECTIVES: Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA. METHODS: Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR). RESULTS: The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. CONCLUSION: Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

Asunto(s)

Glutatión Transferasa/genética , Leucemia Mieloide/genética , Enfermedad Aguda , Adulto , Alelos , Anemia Aplásica/diagnóstico , Anemia Aplásica/etiología , Anemia Aplásica/genética , Estudios de Casos y Controles , Femenino , Eliminación de Gen , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Sustancias Peligrosas/efectos adversos , Humanos , Leucemia Mieloide/epidemiología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/etiología , Síndromes Mielodisplásicos/genética , Factores de Riesgo

RESUMEN

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients with PNH, the aim of this study was to characterize the mutations in the PIG-A gene in Brazilian patients. The analysis of the PIG-A gene was performed using DNA samples derived from bone marrow and peripheral blood. Conformation-sensitive gel electrophoresis was used for screening the mutation and sequencing methods were used to identify the mutations. Molecular analysis permitted the identification of three point mutations in three patients: one G->A transition in the 5' portion of the second intron, one T->A substitution in the second base of codon 430 (Leu430->stop), and one deletion deltaA in the third base of codon 63. This study represents the first description of mutations in the PIG-A gene in a Brazilian population.

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Anciano , Hemoglobinuria Paroxística/genética , Mutación , Cromosoma X/genética , Secuencia de Bases , Brasil , Glicosilfosfatidilinositoles/metabolismo

RESUMEN

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients with PNH, the aim of this study was to characterize the mutations in the PIG-A gene in Brazilian patients. The analysis of the PIG-A gene was performed using DNA samples derived from bone marrow and peripheral blood. Conformation-sensitive gel electrophoresis was used for screening the mutation and sequencing methods were used to identify the mutations. Molecular analysis permitted the identification of three point mutations in three patients: one G-->A transition in the 5' portion of the second intron, one T-->A substitution in the second base of codon 430 (Leu430-->stop), and one deletion DeltaA in the third base of codon 63. This study represents the first description of mutations in the PIG-A gene in a Brazilian population.

Asunto(s)

Hemoglobinuria Paroxística/genética , Proteínas de la Membrana/genética , Mutación/genética , Cromosoma X/genética , Adolescente , Adulto , Anciano , Secuencia de Bases , Brasil , Femenino , Mutación del Sistema de Lectura/genética , Glicosilfosfatidilinositoles/metabolismo , Humanos , Masculino , Mutación Missense/genética

RESUMEN

The prevalence of antithrombin (AT) deficiency in 342 unselected Brazilian patients with venous thrombosis was 1.16%, which increased to 3% when only patients under the age of 50 or with a familial history of thrombosis were considered. In two patients, a clinical (contraceptive use) or genetic risk factor (factor V Leiden and C677T in the methylene tetrahydrofolate reductase gene [MTHFR]) was identified and corroborated the hypothesis that an interaction of factors accounted for the appearance of thrombosis. However, no risk factor other than AT deficiency was identified in one patient with an important clinical and family history of spontaneous thrombosis. Three mutations were identified in these patients: a G-->A transition in intron 5 at position +1 (5'-->3'), three base insertions corresponding to arginine at position 5383 in exon 3A, and a G-->A transition at 13328, corresponding to an Ala404Thr de novo mutation. The polymorphisms in the genes coding for coagulation factors XII and XIII and fibrinogen normally associated with an increased risk for venous thrombosis were not related to thrombosis in these patients. This is the first study in South America to assess the prevalence of AT deficiency and to report the molecular characterization of the mutations involved.

Asunto(s)

Deficiencia de Antitrombina III/genética , Mutación/genética , Trombosis de la Vena/genética , Adulto , Anciano , Antitrombina III/genética , Brasil/epidemiología , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Mutación Puntual , Prevalencia , Sitios de Empalme de ARN , Factores de Riesgo , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología

RESUMEN

Thrombosis is a major clinical feature of the antiphospholipid syndrome. Interactions between genetic and acquired factors could contribute to thrombosis development. In this study, we evaluated 40 patients with antiphospholipid syndrome and thrombosis, 31 primary and nine secondary to systemic lupus erythemathosus, to estimate the carrier rates of factor V Leiden, 20210A --> G prothrombin variant and 677C --> T in the MTHFR gene. Protein C, protein S and antithrombin were measured in 30 patients, with a median of 100.66 +/- 23.86, 93.57 +/- 36.44 and 98.8 +/- 5.67%, respectively. None of the patients were deficient on these natural anticoagulants. No significant variation was found between the patient group and the controls, regarding the prevalence of homozygotes for the mutated 677T allele (2.5 versus 5.4%), or heterozygotes for factor V Leiden (0 versus 0.7%). Despite the fact that these mutations are relatively common in Brazilian thrombophilic patients, its low prevalence in this cohort of patients suggest that these genetic alterations are not risk factors for thrombosis in antiphospholipid syndrome. The prevalence of the mutated allele 20210A of the prothrombin gene was higher in patients when compared with controls (5 versus 0.7%; P = 0.01), suggesting that prothrombin variant could increase the risk of thrombosis in patients with antiphospholipid syndrome.

Asunto(s)

Síndrome Antifosfolípido/complicaciones , Trombofilia/genética , Trombosis/etiología , Adolescente , Adulto , Anciano , Síndrome Antifosfolípido/sangre , Brasil , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Trombofilia/sangre , Trombofilia/etiología

Asunto(s)

Globinas/genética , Mutación Puntual , Talasemia beta/genética , Brasil , Niño , Codón , Femenino , Hemoglobina C/genética , Heterocigoto , Humanos , Talasemia beta/sangre

Asunto(s)

Sustitución de Aminoácidos , Mutación Puntual , Deficiencia de Proteína C/genética , Proteína C/genética , Brasil , Análisis Mutacional de ADN , Femenino , Genes Dominantes , Genes Recesivos , Humanos , Masculino , Linaje , Trombofilia/genética

RESUMEN

Cytomegalovirus (CMV) infection is of major concern in immunocompromised and immunosuppressed patients. Prior to the introduction of HIV-1 antibody screening and efficient virucidal processes to inactivate viruses, individuals with a factor VIII or factor IX deficiency had a high risk of contracting HIV-1 infection through the infusion of contaminated blood products. In addition, blood products were also frequently associated with alterations in immune function. This study investigated the frequency of active CMV infection and its clinical relevance in Brazilian hemophiliacs. One hundred hemophiliacs were screened for the presence of CMV-DNA in their blood using nested PCR. Twenty-five out of 100 patients (25%) were positive for CMV-DNA and 24 of these 100 patients (24%) were HIV-1 positive; 6 of these 24 (25%) were positive for CMV-DNA. A similar frequency was observed among HIV-1-negative patients. In 60 hemophiliacs, the clinical relevance of the CMV infection was assessed. Twenty-one patients were positive for CMV-DNA. Of these, 10 had gastrointestinal bleeding compared to only 9 of 39 patients who were CMV-DNA negative (p = 0.05; chi(2) test). These data indicate a high prevalence of active CMV infection in Brazilian hemophiliac patients, irrespective of whether the patients were or were not infected by HIV-1. There was a possible association between the presence of CMV and the occurrence of gastrointestinal bleeding.

Asunto(s)

Infecciones por Citomegalovirus/complicaciones , Hemorragia Gastrointestinal/etiología , Hemofilia A/complicaciones , Hemofilia B/complicaciones , Brasil , Comorbilidad , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/transmisión , ADN Viral/sangre , Contaminación de Medicamentos , Factor IX/efectos adversos , Factor VIII/efectos adversos , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/virología , Seronegatividad para VIH , Seroprevalencia de VIH , Hemofilia A/epidemiología , Hemofilia B/epidemiología , Humanos , Huésped Inmunocomprometido , Reacción en Cadena de la Polimerasa , Prevalencia , Reacción a la Transfusión , Viremia/complicaciones , Viremia/epidemiología

RESUMEN

BACKGROUND: Iron is suspected to play a role in the development of atherosclerosis and in the progression of the disease, and consequently in myocardial infarction. Authors of a recent study identified a mutation in HLA-H gene, C282Y, that is an excellent marker for hemochromatosis, which is the most common cause of iron overload. There is a high prevalence of carriers of heterozygous hemochromatosis, most of whom are asymptomatic even with abnormalities of iron metabolism. OBJECTIVE: To study C282Y mutation in the HLA-H gene of 173 survivors of myocardial infarction matched with 172 controls by age, race, and sex, and 119 patients upon diagnosis of acute myocardial infarction. METHODS: Identification of the mutation was performed by PCR amplification of the DNA fragment followed by Rsal digestion. RESULTS: The prevalence of heterozygotes for the mutated allele both among patients and among controls was 1.74%. None of the 119 patients studied upon diagnosis was a carrier of the mutation. CONCLUSION: Our data suggested that the most common cause of iron overload is not associated with myocardial infarction.

Asunto(s)

Antígenos HLA/genética , Hemocromatosis/genética , Mutación/genética , Infarto del Miocardio/genética , Adulto , Anciano , Secuencia de Bases , Estudios de Casos y Controles , Estudios de Cohortes , Intervalos de Confianza , Estudios Transversales , Femenino , Hemocromatosis/epidemiología , Heterocigoto , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Infarto del Miocardio/epidemiología , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Sensibilidad y Especificidad

RESUMEN

INTRODUCTION: Several recent studies have analyzed a possible effect of thrombophilia risk factors such as factor V Leiden, the prothrombin variant (allele 20210 A), and homozygosity for thermolabile methylenetetrahydrofolate reductase (MTHFR-T) on the development of ischemic stroke (IS). In the present study, we determined the role of these prothrombotic polymorphisms in the early onset of arterial IS or cerebral venous thrombosis (CVT) in a group of young Brazilian adults of Caucasian and African descent. MATERIALS AND METHODS: We conducted a cross-sectional study of 167 survivors of IS (153 patients with arterial IS and 14 cases of CVT; 66 men: 101 women; 124 of Caucasian and 43 of African origin; median age: 32.6 years; range: 15 to 45 years) and compared the prevalence of inherited thrombophilia risk factors with a control group of 225 sex and age matched individuals of the same ethnic background. To determine the interaction with atherogenic risk factors, the following diagnoses were considered: hypertension, hyperlipoproteinemia, diabetes mellitus, smoking status and use of oral contraceptives. RESULTS: In the arterial IS group, no significant variation was found between patients and controls of Caucasian origin regarding the prevalence of factor V Leiden (P = 0.92), the prothrombin variant (P = 0.13) or homozygosity for MTHFR-T (P = 0.61). Among Brazilians of African descent, 10.3% were homozygous for MTHFR-T, which was significantly elevated, odds ratio of 5.9 (95% CI: 0.88 to 49.15). In the CVT group, two Caucasian patients (20%) were heterozygous for the prothrombin variant, odds ratio of 9.7 (95% CI: 0.95 to 89.71) and one patient was carrier of factor V Leiden (P = 0.49). No prothrombotic polymorphism was identified in patients with CVT of African descent. All women in the CVT group were in use of oral contraceptives or in the post-partum state. DISCUSSION: Inherited thrombophilia risk factors were not found to increase the risk of arterial IS among young patients of Caucasian descent. However, a potential role of homozygosity for MTHFR-T was observed in a small group of patients of African origin. The analysis of patients with CVT revealed an increased risk due to the prothrombin gene variant or oral contraceptive use. Further studies including all incoming patients with IS are necessary to evaluate the impact of inherited thrombophilia risk factors on early mortality.

Asunto(s)

Isquemia/genética , Accidente Cerebrovascular/genética , Trombofilia/genética , Adolescente , Adulto , África/etnología , Alelos , Arterias/patología , Brasil/epidemiología , Anticonceptivos Orales/efectos adversos , Estudios Transversales , Factor V/genética , Salud de la Familia , Femenino , Frecuencia de los Genes , Variación Genética , Homocigoto , Humanos , Isquemia/epidemiología , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Mutación Puntual , Periodo Posparto , Embarazo , Prevalencia , Protrombina/genética , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Trombofilia/epidemiología , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/genética , Población Blanca/genética

RESUMEN

The human platelet antigen (HPA) systems are related to immune platelet disorders as well as to the development of occlusive vascular disease. Several distinct biallelic HPA systems are known, and a heterogeneous distribution of HPA alleles has been described among distinct ethnic groups. In this study we genotyped 320 carefully selected individuals from three distinct ethnic groups in Brazil (Caucasians, Blacks and Amazonian Indians) for the HPA-1, -2, -3, -4 and -5 systems. A similar prevalence for all HPA alleles was found in Brazilians of Caucasian and Black descent. These data contrast with those reported for similar ethnic groups in other countries. Among the Amazonian Indians, no b allele of the HPA-1, -4 and -5 systems was identified. The data presented here could be useful in the diagnosis of alloimmune platelet disease, in genetic counselling and in the development of screening programmes for HPA-related diseases.

Asunto(s)

Antígenos de Plaqueta Humana/genética , Población Negra/genética , Frecuencia de los Genes/genética , Indígenas Sudamericanos/genética , Población Blanca/genética , Adolescente , Adulto , África/etnología , Brasil/epidemiología , Niño , Europa (Continente)/etnología , Femenino , Humanos , Masculino , Persona de Mediana Edad

Asunto(s)

Aminocaproatos/administración & dosificación , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Anciano , Anemia/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Femenino , Fibrinólisis/efectos de los fármacos , Hemorragia/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

The ability of circulating progenitor cells to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin) in 63 patients with sickle cell disease (SCD) (36 homozygotes for hemoglobin [Hb] S, 13 double heterozygotes for Hb S and beta thalassemia, and 14 SC patients) in Southeast Brazil. In the presence of growth factors, SCD patients (all genotypes) presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5 x 10(5) MNC), when compared with control subjects. However, when the progenitor cells were cultured in the absence of added stimulus, high numbers of BFU-E were observed only in the genotypes SS and S/beta thalassemia. SC patients presented a similar response to the control subjects. Moreover, there was an inverse correlation between spontaneous (without stimulus) BFU-E and Hb levels in SCD patients. These results suggest that the formation of spontaneous BFU-E observed in SCD may be due to an expanded erythropoiesis secondary to hemolysis.

Asunto(s)

Anemia de Células Falciformes/sangre , Células Precursoras Eritroides/citología , Adulto , Brasil , Diferenciación Celular , División Celular , Ensayo de Unidades Formadoras de Colonias , Eritropoyetina/farmacología , Genotipo , Enfermedad de la Hemoglobina SC/sangre , Enfermedad de la Hemoglobina SC/genética , Humanos , Proteínas Recombinantes , Rasgo Drepanocítico/sangre , Rasgo Drepanocítico/complicaciones , Rasgo Drepanocítico/genética , Talasemia beta/sangre , Talasemia beta/complicaciones , Talasemia beta/genética

Asunto(s)

Fibrina/deficiencia , Fibrina/genética , Trombosis/genética , Adulto , Brasil , Humanos , Masculino , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADN

Asunto(s)

Deficiencia de Proteína S/genética , Adulto , Codón sin Sentido , Humanos , Masculino , Linaje , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple , Trombosis/genética