RESUMEN
BACKGROUND: Pigmented lesions are uncommon in the oral mucosa, and studies investigating the incidence and types of these lesions are desired to improve the diagnostic knowledge of clinicians. The aim of this study was to analyze the distribution of oral pigmented lesions in a Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. Oral pigmented lesions were retrieved from the files of two oral and maxillofacial pathology services from Brazil over a 45-year period (1974-2019). The clinical data and the diagnoses of each case were retrieved and included in a Microsoft Excel® database. RESULTS: From 77.074 lesions diagnosed in this period, 761 (0.99%) represented pigmented lesions of the oral mucosa, including 351 (46.1%) melanocytic and 410 (53.9%) non-melanocytic lesions, with a higher incidence in females (73.2%) between the fourth and seventh decades of life. Amalgam tattoo (53.6%) represented the most common lesion, followed by melanotic macule (18.3%) and racial pigmentation (10.8%). Other pigmented lesions included nevus (9.9%), post-inflammatory pigmentation (3%), melanoma (2.1%), melanoacanthoma (1.4%), smoker's melanosis (0.4%), drug-induced pigmentation (0.3%), and melanotic neuroectodermal tumor of infancy (0.1%). The buccal mucosa was the most commonly affected site (25.2%), followed by the alveolar ridge (14.5%), and gingiva (11.8%). CONCLUSIONS: The current findings were similar to previous studies with minor differences due methodology and characteristics of the services from where lesions were retrieved. The knowledge of these data may contribute to a better understanding of oral pigmented lesions and assist clinicians to better recognize and manage them.
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Enfermedades de la Boca , Brasil/epidemiología , Estudios Transversales , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/epidemiología , Mucosa Bucal , Estudios RetrospectivosRESUMEN
BACKGROUND: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas. MATERIAL AND METHODS: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed. RESULTS: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months. CONCLUSIONS: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.
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Melanoma , Neoplasias de la Boca , Adulto , Anciano , Brasil/epidemiología , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/epidemiología , Persona de Mediana Edad , Neoplasias de la Boca/epidemiología , Estudios RetrospectivosRESUMEN
The impaired bioavailability of endogenous nitric oxide (NO) in sickle cell anemia (SCA) may be influenced by polymorphisms in the endothelial nitric oxide synthase gene (eNOS). We compared allelic/genotypic frequencies of the eNOS polymorphisms T-786C, VNTR4a/b and G894T between 89 adult SCA patients and 100 healthy controls, and investigated the relationship between these SNPs and markers of hemolysis [lactate dehydrogenase (LDH), indirect bilirubin (IB) and reticulocyte counts], inflammation [interleukins IL-1ß, IL-6, IL-8, Tumor Necrosis Factor (TNF-α) and C-reactive protein (CRP)] and endothelial dysfunction (ED) [soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L-selectin (sL-selectin), von Willebrand Factor (vWF) antigen and D-dimers] in the patients. The frequencies of the mutant -786C allele and -786C/C genotype were significantly higher in patients (p = 0.02 and p = 0.04, respectively) but not significantly correlated with the markers. For VNTR4a/b and G894T, the allelic/genotypic frequencies did not statistically differ between patient and control groups. Patients carrying the 4a allele and those with the 894G/G genotype showed a significant decrease in IB (p = 0.02 and p = 0.04, respectively), and only patients with the 4a allele exhibited reduced IL-1ß (p = 0.01). The correlation profiles between markers of inflammation and ED significantly differed between patients carrying the mutant alleles and those with wild-type genotypes. This appears to be the first report on the relationship between eNOS gene polymorphisms and markers of hemolysis, inflammation and ED in Brazilian SCA patients. Our results indicate that the SNPs analyzed may influence the phenotypic variability of these patients.
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Anemia de Células Falciformes/enzimología , Anemia de Células Falciformes/genética , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hemólisis , Molécula 1 de Adhesión Intercelular/sangre , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple , Molécula 1 de Adhesión Celular Vascular/sangre , Factor de von Willebrand/análisis , Adulto , Alelos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/epidemiología , Bilirrubina/sangre , Biomarcadores/sangre , Brasil/epidemiología , Estudios de Casos y Controles , Citocinas/sangre , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Inflamación/sangre , L-Lactato Deshidrogenasa/sangre , Masculino , Recuento de Reticulocitos , Adulto JovenRESUMEN
BACKGROUND: Sickle leg ulcer (SLU) is a chronic and debilitating complication of sickle cell disease (SCD) associated with huge physical and psychosocial discomfort. The occurrence of SLU has remained steady despite successful preventive strategies and advances in SCD care. Although multifactorial factors have been implicated in SLU, these are not fully understood, and data on how these relate to young Nigerian SCD patients are scanty. AIMS: This study aims to evaluate the sociodemographic, clinical, and laboratory markers of SLU in a young Nigerian SCD cohort. PATIENTS AND METHODS: This study involved 109 young SCD patients and 67 healthy peers. The sociodemographic and laboratory parameters of the participants were examined in addition to the evaluation of the SCD cohort for SLU. RESULTS: Only the HbSS patients had SLU. This was found in six of them giving a prevalence of 5.9% (6/101). Their median age was 17, range 14-21 years. There was a preceding history of trauma in 4 (66.7%), and this included a case of traditional scarifications for local therapeutic purposes. Two of the three (66.7%) males with SLU also had priapism (P = 0.0132). Patients with SLU were older, had less frequent bone pain crises, and significantly belonged to the low socioeconomic class (P < 0.05). Although patients with SLU had relatively higher lactate dehydrogenase, platelet count, aspartate transaminase, bilirubin, white blood cell, and lower Hb concentration and HbF, these did not attain statistical significance (P > 0.05). CONCLUSION: This study confirms that SLU is common among young SCD patients with HbSS genotype, low socioeconomic background, and older age. It also suggests that SLU could be more related to hemolysis-associated SCD phenotypes among the patients.
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Anemia de Células Falciformes/complicaciones , Bilirrubina/sangre , Población Negra/estadística & datos numéricos , Úlcera de la Pierna/etiología , Adolescente , Adulto , Anciano , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/epidemiología , Biomarcadores , Estudios de Cohortes , Femenino , Humanos , Úlcera de la Pierna/sangre , Úlcera de la Pierna/epidemiología , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Recuento de Plaquetas , Prevalencia , Priapismo , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Adulto JovenRESUMEN
Chili pepper (Capsicum chinense) is a great economic important culture on the State of Amazonas, and it represents, approximately, a production of 1.9 thousand tons per year. It is one of the hosts of Colletotrichum genus in the North region of Brazil. The aim of the study was to differentiate and to identify isolates of Colletotrichum collected from C. chinense in Amazon. Molecular characterization, using RFLP-PCR, ERIC-PCR and ISSR, was carried out initially for screening of morphologically similar isolates. Furthermore, phylogenetic analyses were performed using combined regions: Actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for the three isolates, INPA 2066, INPA 2286 and INPA 1858, plus superoxide dismutase (SOD2) for INPA 2066. We showed that the molecular markers were able to distinguish the isolates of Colletotrichum studied and these results were confirmed with the phylogenetic analyses, three different occurrences of Colletotrichum species (C. siamense, C. scovillei and C. brevisporum) causing anthracnose in C. chinense in the State of Amazonas. This study represents the first report of the species C. siamense and C. scovillei in this host in Brazil.
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Capsicum/microbiología , Colletotrichum/genética , Filogenia , Polimorfismo Genético , Actinas/genética , Colletotrichum/clasificación , Colletotrichum/aislamiento & purificación , Colletotrichum/patogenicidad , Proteínas Fúngicas/genética , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/genética , Repeticiones de Microsatélite , Superóxido Dismutasa/genéticaAsunto(s)
Anemia Hemolítica , Hemoglobinas Anormales , Mutación , Adulto , Anemia Hemolítica/sangre , Anemia Hemolítica/genética , Anemia Hemolítica/patología , Anemia Hemolítica/terapia , Brasil , Femenino , Hemoglobinas Anormales/química , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/metabolismo , HumanosRESUMEN
OBJECTIVE: The objectives of this present case study are to report a rare combination of a displaced talar neck fracture with a compression fracture of the calcaneocuboid joint in a 5-year-old child and to describe its radiological features, surgical treatment and clinical outcome. A 5-year-old male boy was injured in a car accident in which his left foot underwent one of the tires. On arrival at the hospital, a displaced talar neck fracture associated both with a cuboid fracture and compression of the articular surface of the cuboid at the calcaneocuboid join was identified. Fractures were fixed surgically. Leg was protected with a below-knee plaster split immobilization and non-weight-bearing for 5 weeks. After that period, the patient initiated a rehabilitation protocol with active and passive motion exercises. DISCUSSION: Fractures and fracture dislocations at the mid-tarsal joint have an important impact on the global foot function because malunion can result in post-traumatic arthritis and three-dimensional deformities of the foot. If a cuboid compression fracture is not reduced properly, it can result in the shortening of the lateral column with the development of an abduction, pronation and flat foot deformity. A talar neck fracture, if unreduced, can result in medial column displacement and rotational dislocation of the talar head, leading to a subluxation in the talonavicular joint with severe restriction of foot function. With early surgical treatment and open reduction and internal fixation, our patient recovered from the accident without having symptoms of pain, avascular necrosis, postoperative foot deformities or neurovascular deficits. CONCLUSIONS: The combination of a displaced talar neck fracture with a compression fracture of the calcaneocuboid joint in children usually requires correct diagnoses and early treatment with anatomic reduction and internal fixation to prevent severe post-traumatic deformities. LEVEL OF EVIDENCE: V.
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Fracturas Óseas/complicaciones , Fracturas por Compresión/complicaciones , Traumatismo Múltiple , Astrágalo/lesiones , Articulaciones Tarsianas/lesiones , Preescolar , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/cirugía , Humanos , Masculino , Traumatismo Múltiple/diagnóstico por imagen , Traumatismo Múltiple/cirugía , Radiografía , Astrágalo/diagnóstico por imagen , Astrágalo/cirugía , Articulaciones Tarsianas/diagnóstico por imagen , Articulaciones Tarsianas/cirugíaRESUMEN
Phosphatidylinositol phosphate kinases (PIPKs) are enzymes that participate in diverse intracellular signaling pathways. They are classified into 3 functionally distinct subfamilies - PIPKI (α, ß, γ), PIPKII (α, ß, γ), and PIPKIII - located in various subcellular compartments. Recently, the PIPKIIα and ß-globin genes were found to be overexpressed in reticulocytes from 2 siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIa and the production of globins. The main aim of this study was to determine the expression profiles of PIPK genes in healthy individuals during in vitro erythropoiesis using quantitative real-time polymerase chain reaction and to compare these profiles with profiles of globin genes. Our results showed that expression of all PIPKs increases as the cells differentiate, coinciding with the expression profiles of globins. Analysis of the effects of globins on PIPK genes revealed that they varied significantly between the globins, the most noticeable being the effect of α-globin on PIPKIIα (P < 0.0001) and γ-globin on PIPKIIγ (P < 0.0001). The relationship between the expression of PIPKs and globin genes was statistically significant, particularly between PIPKIIα and α-globin (P = 0.0002) and PIPKIIγ and ß-globin (P < 0.0001). Linear correlation analysis revealed a strong relationship between PIPKIIα and α-globin genes. This study is the first to establish the expression profiles of PIPK genes during in vitro erythropoiesis in healthy individuals and suggests a parallel between the expression of PIPK and globin genes, reinforcing the hypothesis that they may be related.
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Eritropoyesis/genética , Perfilación de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adulto , Área Bajo la Curva , Globinas/genética , Globinas/metabolismo , Humanos , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismoAsunto(s)
Eliminación de Secuencia , Talasemia alfa , Humanos , Talasemia alfa/genética , Brasil , Masculino , Globinas alfa/genética , Niño , Femenino , Hemoglobina H/genéticaRESUMEN
1. The major effect associated with hydroxyurea (HU) treatment of sickle cell anaemia (SCA) patients is an increase in fetal haemoglobin (HbF) synthesis, which inhibits the polymerization of haemoglobin S. 2. Hydroxyurea improves clinical symptoms by reducing the frequency of pain and vaso-occlusive crises, acute chest syndrome, transfusion requirements and hospitalization. 3. The molecular mechanisms responsible for HU-mediated induction of fetal globin transcription are not completely understood. Therefore, the aim of the present study was to identify differentially expressed genes participating in these mechanisms. 4. We established two suppression subtractive hybridization (SSH) libraries from reticulocytes obtained from SCA patients either not on or on HU treatment. The gene expression of some of the genes identified was subsequently evaluated by real-time polymerase chain reaction (PCR). 5. Genes identified with altered expression included SUDS3, FZD5 and PHC3, which may be associated with the regulation of globin expression. 6. This is the first demonstration of an association between HU treatment and the expression of genes identified in erythroid cells.
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Perfilación de la Expresión Génica , Hidroxiurea/farmacología , Reticulocitos/efectos de los fármacos , Reticulocitos/metabolismo , Rasgo Drepanocítico/metabolismo , Adulto , Femenino , Regulación de la Expresión Génica , Biblioteca de Genes , Humanos , MasculinoRESUMEN
SETTING: Four hundred and sixty-eight isoniazid (INH) resistant Mycobacterium tuberculosis isolates recovered from a selected Brazilian population. OBJECTIVE: To check for susceptibility to other chemotherapeutic drugs used in TB treatment, and to ascertain mutations involved in INH and rifampicin (RMP) resistance. DESIGN: Antimicrobial susceptibility to RMP, streptomycin and ethambutol (EMB) was evaluated by the resistance ratio method and pyrazinamide (PZA) by activity assay. Single strand conformation polymorphism (SSCP) and sequence analysis were performed in samples from this panel to confirm mutations in codon 315 of the katG and in a 69-bp region of the rpoB gene. RESULTS: Combined resistance to INH+RMP, INH+ PZA, INH+EMB, and INH+RMP+PZA was shown in respectively 272 (58.1%), 126 (26.9%), 47 (10%), 116 (24.8%) isolates. No katG mutation was found in 19 (39.6%) of 48 strains tested. Ser315Thr substitution was found in 29 (60.4%). All RMP-resistant strains tested (n = 25) showed rpoB mutations. S531L substitution was found in 15 (60%). CONCLUSION: INH-resistant strains isolated from selected Brazilian populations frequently show resistance to other first-line anti-tuberculosis drugs. rpoB mutation was responsible for RMP resistance in all strains. Among INHr strains, katG mutations were shown in only 60.4%. Genetic approaches targeting the rpoB gene but not the katG gene have a high sensitivity to detect resistance among Brazilian M. tuberculosis strains.
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Antituberculosos/farmacología , Isoniazida/farmacología , Mycobacterium tuberculosis/genética , Rifampin/farmacología , Proteínas Bacterianas/genética , Brasil , Catalasa/genética , Análisis Mutacional de ADN , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Microbiana , Humanos , Mycobacterium tuberculosis/patogenicidad , Polimorfismo Conformacional Retorcido-Simple , Prevalencia , Análisis de Secuencia de ADN , Tuberculosis Resistente a Múltiples MedicamentosRESUMEN
The study aimed to analyze the Colossoma macropomum reproductive behavior and quality of the female gametes throughout the reproductive season. The experiment was carried out in Pimenta Bueno - Rondônia State (Northern Brazil) during the reproductive season (2010-2011) using 36 females. Each sampling was performed on a 15 ± 5 days interval. Female gametes were collected by stripping and the following analyses were performed: weight of oocytes released (g); productivity index, fertilization and hatching rate. During the sampling period was verified effect (p < 0.05) of collecting time into the season for oocytes weight, productivity index and fertilization rate. Although the period 3 (December) did not differ significantly from other periods, it showed better parameters for the quality of C. macropomum oocytes.
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Characidae/fisiología , Oocitos/fisiología , Reproducción/fisiología , Animales , Peso Corporal , Brasil , Characidae/clasificación , Femenino , Masculino , Estaciones del AñoRESUMEN
O objetivo foi avaliar protocolos de maturação in vitro (MIV) para oócitos de cutias, seguida de fertilização in vitro (FIV) e ativação partenogenética (AP). Os oócitos imaturos (CCOs) foram obtidos por fatiamento do ovário, após OSH, e submetidos a três grupos: MAT - 16 (16 horas de maturação), MAT - 20 (20 horas de maturação) e MAT - 24 (24 horas de maturação), em incubadora de cultivo a 38,8°C, com atmosfera de 5% de CO2 e 95% de umidade relativa. A maturação foi analisada pela presença do primeiro corpúsculo polar. Em seguida, os CCOs maduros foram submetidos à FIV, com período de coincubação dos CCOs e dos espermatozoides de 15h, a 38,8ºC e 5% de CO2, e AP com ionomicina. Os grupos de MIV foram analisados utilizando-se o teste qui-quadrado e, nos experimentos de FIV e AP, foram analisadas a taxa de clivagem e a proporção de desenvolvimento embrionário. A análise estatística foi realizada utilizando-se o programa SAS. Houve diferença significativa entre os grupos de maturação, tendo os grupos MAT - 20 e MAT - 24 apresentado maior porcentagem de oócitos maturados in vitro. As taxas de clivagem e de desenvolvimento embrionário foram de 8,6% e 2,9%, respectivamente, na FIV, e de 63,6% e 15,1%, na AP. Entretanto, nos dois casos, o embrião não passou do estágio de mórula.(AU)
The objective was to evaluate IVM protocols for agouti oocytes, followed by in vitro fertilization (IVF) and parthenogenetic activation (PA). The immature oocytes (CCOs) were obtained by slicing the ovary after OSH and submitted to three groups: MAT - 16 (16 hours maturation), MAT - 20 (20 hours maturation) and MAT - (24 hours maturation), in a culture incubator at 38.8°C, with an atmosphere of 5% CO2 and 95% relative humidity. The maturation was analyzed by the presence of the first polar corpuscle. Then, mature CCOs were submitted to IVF, with co-incubation period of CCOs and spermatozoa from 15h to 38.8°C and 5% of CO2, and PA with inomycin. The IVM groups were analyzed using the chi-square test and in the FIV and PA experiment the rate of cleavage and the rate of embryonic development were analyzed. Statistical analysis was performed using the SAS program. There was a significant difference between the maturation groups, and the MAT - 20 and MAT - 24 groups showed a higher percentage of matured oocytes in vitro. The rates of cleavage and embryonic development were 8.6% and 2.9%, respectively in FIV and 63.6% and 15.1% in PA. However, in both cases the embryo did not pass beyond the morula stage.(AU)
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Animales , Oocitos , Fertilización In Vitro/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Dasyproctidae , Partenogénesis , IonomicinaRESUMEN
We describe here a new frameshift mutation of ß-thalassemia in a Uruguayan family with Italian ancestry [ß48 (-T); HBB:c.146delT]. This frameshift results in formation of premature stop codon (TGA) 40 bp downstream and in a short unstable product that is degraded in the cell.
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Salud de la Familia , Mutación del Sistema de Lectura , Globinas beta/genética , Talasemia beta/genética , Adulto , Codón sin Sentido , Exones , Femenino , Eliminación de Gen , Heterocigoto , Humanos , Italia , Linaje , Estabilidad Proteica , Uruguay , Población Blanca , Globinas beta/análisis , Globinas beta/metabolismo , Talasemia beta/sangre , Talasemia beta/metabolismoRESUMEN
The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.
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Ejercicio Físico/fisiología , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple , Posmenopausia/genética , Posmenopausia/metabolismo , Presión Sanguínea/fisiología , Distribución de Chi-Cuadrado , Método Doble Ciego , Femenino , Genotipo , Humanos , Lípidos/sangre , Malondialdehído/sangre , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Estrés Oxidativo/fisiología , Factores de TiempoRESUMEN
OBJECTIVE: To identify clinical and genetic risk factors for moderate hyperbilirubinemia during the first week of life. STUDY DESIGN: Using univariate and multivariate multiple regression analyses, the RR for clinical factors, the African variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency (G202A/A376G), and (TA)(n) UGT1A1 polymorphisms were established in a cohort of 608 Brazilian newborn infants. Hyperbilirubinemia was monitored until 134.5 ± 49.8 h of life (IQR, 111.0 to 156.7). The dependent variable was total bilirubinemia (TB) ≥12.9 mg per 100 ml estimated by transcutaneous or plasma bilirubin measurements. RESULT: The African variant of G6PD deficiency and (TA)(7)/(TA)(7) and (TA)(7)/(TA)(8) polymorphisms present in 6.1 and 12.0% of newborns, respectively, were not risk factors for moderate hyperbilirubinemia. Coexpression of G6DP deficiency and UGT1A1 polymorphisms occurred in 0.49% of the subjects. Independent clinical predictors for TB≥ 12.9 mg per 100 ml were gestational age <38 weeks and reference curve percentiles >P40th. CONCLUSION: In this study, G6PD deficiency and UGT1A1 gene promoter polymorphisms were not risk factors for moderate hyperbilirubinemia. Genetic factors may vary considerably in importance among different populations.
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Comparación Transcultural , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/genética , Brasil , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Tamización de Portadores Genéticos , Genotipo , Deficiencia de Glucosafosfato Deshidrogenasa/diagnóstico , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Glucuronosiltransferasa/genética , Humanos , Recién Nacido , Kernicterus/diagnóstico , Kernicterus/genética , Masculino , Tamizaje Neonatal , Polimorfismo Genético/genética , Estudios Prospectivos , Factores de RiesgoRESUMEN
The JAK2 V617F mutation, present in the majority of polycythemia vera (PV) patients, causes constitutive activation of JAK2 and seems to be responsible for the PV phenotype. However, the transcriptional changes triggered by the mutation have not yet been totally characterized. In this study, we performed a large-scale gene expression study using serial analysis of gene expression in bone marrow cells of a newly diagnosed PV patient harboring the JAK2 V617F mutation and in normal bone marrow cells of healthy donors. JUNB was one of the genes upregulated in PV, and we confirmed, by quantitative real-time PCR, an overexpression of JUNB in hematopoietic cells of other JAK2 V617F PV patients. Using Ba/F3-EPOR cell lines and primary human erythroblast cultures, we found that JUNB was transcriptionally induced after erythropoietin addition and that JAK2 V617F constitutively induced JunB protein expression. Furthermore, JUNB knockdown reduced not only the growth of Ba/F3 cells by inducing apoptosis, but also the clonogenic and proliferative potential of human erythroid progenitors. These results establish a role for JunB in normal erythropoiesis and indicate that JunB may play a major role in the development of JAK2 V617F myeloproliferative disorders.