RESUMEN
INTRODUÇÃO E/OU FUNDAMENTO: A acromegalia é uma doença endócrina rara causada por adenoma hipofisário secretor de Hormônio do Crescimento (GH), cursando com aumento dos níveis plasmáticos de GH e, consequentemente, do Fator de Crescimento Semelhante à Insulina-1 (IGF-1). Ambos os hormônios exercem importantes atividades regulatórias no sistema cardiovascular (CV) que é o principal responsável pelas complicações clínicas da síndrome. O relato de caso a seguir expõe diversas dessas complicações. MÉTODOS: Relatamos caso de paciente do sexo feminino, 47 anos, branca, tabagista, sem outras comorbidades, que procurou atendimento por cansaço progressivo, associado à dispneia aos esforços e edema de membros inferiores. RESULTADOS: O ecocardiograma transtorácico confirmou dupla lesão mitral grave, com predomínio de estenose, tratada cirurgicamente com implante de prótese mitral biológica. Cinco anos após, a paciente desenvolveu hipertensão arterial (HA) estágio 1, tratada com Hidroclorotiazida. Concomitantemente relatou cefaleia, perda visual bitemporal, separação dos dentes, aumento de extremidades (com necessidade de aumentar numeração dos sapatos) e língua. Com suspeita clínica de acromegalia, foi submetida a investigação que evidenciou elevação de níveis plasmáticos de GH e IGF1 e lesão expansiva intrasselar identificada por ressonância magnética nuclear. Iniciou-se tratamento com Bromocriptina. Nesse período a paciente interrompeu o uso da medicação anti-hipertensiva, mantendo controle adequado da pressão arterial. No entanto, três anos depois, foi constatado novo aumento dos níveis de IGF-1 para 785mcg/L (VR 2,5 segundos, sendo indicado e realizado implante de marcapasso definitivo. CONCLUSÕES: A doença CV é a comorbidade mais frequente e a principal causa de morte relacionada a acromegalia. O caso apresentado reúne e ilustra as principais manifestações CV da acromegalia: doença valvar; hipertrofia ventricular esquerda; bradiarritmias e HA, muito embora não tenha sido possível afastar doença reumática como etiologia da dupla lesão mitral. A prevalência de HA varia de 13 a 60% e contribui significativamente com o excesso de morbimortalidade observado. A alta prevalência de HA na população geral faz com que seja árduo discernir na prática clínica em que medida a HA é secundária a acromegalia, essencial ou mista. O controle pressórico obtido concomitantemente com a redução dos níveis plasmáticos de GH e IGF-1 indica uma associação direta destes hormônios com a HA em função do aumento da resistência insulínica, da reabsorção renal de sódio e da atividade simpática. Por outro lado, a persistência da HA após o controle hormonal obtido com o Octreotide sugere que nessa fase mais tardia, o remodelamento arteriolar tenha levado a instalação de HA primária.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Acromegalia , Ecocardiografía Transesofágica , Adenoma Hipofisario Secretor de Hormona del Crecimiento , HipertensiónRESUMEN
INTRODUÇÃO E/OU FUNDAMENTO: A suplementação de vitamina D em indivíduos sem déficit aumentou significativamente nos últimos anos. Nos Estados Unidos a taxa de prescrição aumentou 30% ao longo de 10 anos. Contribuem para o fenômeno movimentos de opinião sustentando propriedades terapêuticas não comprovadas e a percepção geral de segurança e inocuidade. MÉTODOS: Relatamos um caso de intoxicação grave por vitamina D secundária a suplementação inadequada, inicialmente diagnosticada pela constatação de picos hipertensivos em paciente previamente normotensa. RESULTADOS: Paciente M.C.N., do sexo feminino, 60 anos, com história pregressa de fibromialgia, osteoartrite e depressão, mantinha acompanhamento com reumatologista e uso regular de trazodona, pregabalina e duloxetina. Após dosagem em consulta de rotina (vitamina D = 39ng/mL), recebeu prescrição de suplementação oral de colecalciferol (5000 UI/dia) por tempo indeterminado. Três semanas depois, a paciente, previamente normotensa, constatou picos hipertensivos e evoluiu com prurido generalizado, dor abdominal, náuseas e vômitos. Investigação inicial revelou hipercalcemia (cálcio total corrigido 13mg/ dL), injúria renal aguda (creatinina 2,3mg/dL) e hipertensão arterial (HA) confirmada em Monitorização Ambulatorial da Pressão Arterial (MAPA) de 24 horas. A tomografia de abdome não evidenciou alterações significativas e os sintomas digestivos foram atribuídos ao quadro metabólico. A dosagem de vitamina D confirmou a hipótese de intoxicação iatrogênica e Hipervitaminose D (vitamina D = incalculável). Após internação hospitalar, hidratação parenteral, suspensão da vitamina D e medidas para hipercalcemia, a paciente apresentou melhora progressiva da função renal e remissão dos sintomas. No entanto, mesmo após a resolução do quadro, a HA persiste até o momento, sendo necessárias para seu controle duas classes de anti-hipertensivos. CONCLUSÕES: Quase 500 anos atrás, o médico suíço Paracelso escreveu que "a diferença entre remédio e veneno está na dose". A incidência de intoxicação por vitamina D vem aumentando globalmente, seja por erro de manipulação, erro de prescrição ou uso suplementar em altas doses. Doses acima de 4000 UI/dia em períodos prolongados ou 10000 UI/ dia em períodos mais curtos foram associadas a elevação suprafisiológica do nível sérico (>150 ng/ml). O grau de intoxicação observado no caso apresentado parece desproporcional ao nível de suplementação e não podemos excluir erro de manipulação ou de uso. A associação entre Hipervitaminose D e HA é mediada tanto pela hipercalcemia como pela injuria renal. No entanto, neste caso a HA se manteve após resolução dos gatilhos iniciais, sugerindo que possam estar implicados outros mecanismos ainda não esclarecidos.
RESUMEN
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation Control (C) and High-fat (H). Post- weaning Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º lifes day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação Controle (C) e Hiperlipídica (H). Pós-desmame Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.
Asunto(s)
Femenino , Animales , Ratas , Dieta Alta en Grasa/efectos adversos , Dieta Alta en Grasa/veterinaria , Dopamina/análisis , Neuropéptido Y/análisis , Proopiomelanocortina/análisis , Ratas WistarRESUMEN
Abstract Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation Control (C) and High-fat (H). Post-weaning Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º lifes day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
Resumo A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação Controle (C) e Hiperlipídica (H). Pós-desmame Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.
RESUMEN
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação Controle (C) e Hiperlipídica (H). Pós-desmame - Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.
Asunto(s)
Animales , Femenino , Embarazo , Ratas , Proopiomelanocortina/genética , Dieta Alta en Grasa/efectos adversos , Peso Corporal , Neuropéptido Y/genética , Expresión Génica , Receptores Dopaminérgicos/genética , Ratas Wistar , Preferencias AlimentariasRESUMEN
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning - Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
Asunto(s)
Dieta Alta en Grasa , Proopiomelanocortina , Animales , Peso Corporal , Dieta Alta en Grasa/efectos adversos , Femenino , Preferencias Alimentarias , Expresión Génica , Neuropéptido Y/genética , Embarazo , Proopiomelanocortina/genética , Ratas , Ratas Wistar , Receptores Dopaminérgicos/genéticaRESUMEN
Approximately 10-15% of all pregnancies end in spontaneous abortions. Many factors can lead to embryonic loss; however, it has been well established that over 50% of all miscarriages result from chromosomal abnormalities, primarily aneuploidies (>96%). Identifying the cause of miscarriage can significantly reduce the psychological stress in women, and enable better genetic counseling for a future pregnancy. Quantitative fluorescent polymerase chain reaction (QF-PCR) has been previously used in the study of chromosomal abnormalities. In this retrospective study, the frequency of aneuploidy in samples of 130 miscarriages undergone by patients (age average: 34.1 ± 4.6 years) at our institution was determined by QF-PCR using short tandem repeat markers. The gender of the miscarriage cases was determined by amplifying the amelogenin locus (70 males and 60 females). Seventy-one of these cases (54.6%) presented aneuploidies such as trisomy, monosomy, triploidy, and double trisomy. Trisomy 22 was the most common aneuploidy (present in 14 cases), followed by trisomy 15, trisomy 16, and monosomy X. We also observed monosomy at chromosomes X and 21 and a case with multiple aneuploidies at chromosomes 16 and 22. The most common aneuploidies associated with miscarriages were detected by QF-PCR; therefore, we concluded that QF-PCR is a rapid and reliable method for the detection of aneuploidy, and can be used as an accessory to the widely used karyotype analysis.
Asunto(s)
Aborto Espontáneo/genética , Aneuploidia , Repeticiones de Microsatélite/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto , Cromosomas Humanos Par 22/genética , Electroforesis en Gel de Agar , Femenino , Fluorescencia , Marcadores Genéticos , Humanos , Masculino , Embarazo , Estudios Retrospectivos , Trisomía/genética , Síndrome de Turner/genéticaRESUMEN
Some cases of recurrent first trimester miscarriage have a thrombotic etiology. The aim of this study was to investigate the prevalence of the most common thrombophilic mutations - factor V (FV) Leiden G1691A (FVL), prothrombin (FII) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T - in women with recurrent miscarriages. In this case-control study, we included 137 women with two or more consecutive first-trimester miscarriages (£12 weeks of gestation) and 100 healthy women with no history of pregnancy loss, and with at least one living child. DNA was extracted from the patient samples, and the relevant genes (FVL, FII, and MTHFR) were amplified by PCR, followed by restriction fragment length polymorphism, to assess the polymorphisms in these genes. The allelic frequencies of polymorphisms were not significantly different between the case and control groups. Polymorphisms in the MTHFR, FVL, and FII genes were not associated with recurrent miscarriage during the first trimester of pregnancy in Brazilian women (P = 0.479; P = 0.491 and P = 0.107, respectively). However, the etiologic identification of genetic factors is important for genetic counseling.
Asunto(s)
Aborto Habitual/genética , Factor V/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Longitud del Fragmento de Restricción , Protrombina/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , EmbarazoRESUMEN
INTRODUCTION: Cisplatin is an effective chemotherapeutic agent commonly used in the treatment of malignant tumours, but ototoxicity is a significant side effect. OBJECTIVES: To discuss the mechanisms of cisplatin ototoxicity and subsequent cell death, and to present the results of experimental studies. MATERIAL AND METHODS: We conducted a systematic search for data published in national and international journals and books, using the Medline, SciELO, Bireme, LILACS and PubMed databases. RESULTS: The nicotinamide adenine dinucleotide phosphate oxidase 3 isoform (also termed NOX3) seems to be the main source of reactive oxygen species in the cochlea. These reactive oxygen species react with other molecules and trigger processes such as lipid peroxidation of the plasma membrane and increases in expression of the transient vanilloid receptor potential 1 ion channel. CONCLUSION: Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Cóclea/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Cóclea/metabolismo , Enfermedades Cocleares/inducido químicamente , Humanos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Oral squamous cell carcinoma (OSCC) is a worldwide health problem because it is a great cause of cancer morbidity and mortality. The transforming growth factor-ß1 (TGF-ß1) is involved in the regulation of numerous immunomodulatory processes. Thus, the aim of this case-control study was to investigate the possible association between the TGF-ß1T869C polymorphism and oral cancer. The genomic DNA extracted from peripheral blood of 62 male smoker patients diagnosed with OSCC and 62 smokers without cancer was analysed. The C allele was significantly more prevalent in the oral cancer group than in the controls, and individuals carrying this allele had an estimated 2.73-fold greater relative risk of developing cancer compared with C allele noncarriers (OR = 2.73, 95% CI = 1.19-6.28). Although T allele was not statistically significant among the controls, considering the genotypic analysis, the TT homozygous genotype showed a protector effect in relation to oral cavity cancer (OR = 0.37, 95% CI = 0.16-0.84). Some clinicopathological features were also analysed for genotype distribution, and no significant differences were observed: tumour size (P > 0.70), nodal status (P > 0.10) and tumour stage (P > 0.70). This is the first report of a study assessing the importance of T869C TGF-ß polymorphism in oral cancer. It is known that the TGF-ß T869C variation results in a Leu10Pro substitution in the signal peptide sequence. Our results suggested that the C allele could increase TGF-ß secretion which suppresses antitumour immune responses and may affect the OSCC risk.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/genética , Factor de Crecimiento Transformador beta1/genética , Adulto , Alelos , Secuencia de Bases , Carcinoma de Células Escamosas/inmunología , Estudios de Casos y Controles , Frecuencia de los Genes , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Neoplasias de la Boca/inmunología , Polimorfismo de Nucleótido Simple , Señales de Clasificación de Proteína/genética , Análisis de Secuencia de ADN , FumarRESUMEN
Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and Interleukin 8 (IL-8) -251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 -251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha -308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, beta(S)-globin gene haplotypes and α2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome.
Asunto(s)
Anemia de Células Falciformes/sangre , Biomarcadores/sangre , Interleucina-8/sangre , Anamnesis , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/sangre , Adolescente , Adulto , Alelos , Anemia de Células Falciformes/genética , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Haplotipos , Humanos , Interleucina-8/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Fetal hemoglobin (HbF), encoded by the HBG2 and HBG1 genes, is the best-known genetic modulator of sickle cell anemia, varying dramatically in concentration in the blood of these patients. This variation is partially associated with polymorphisms located in the promoter region of the HBG2 and HBG1 genes. In order to explore known and unknown polymorphisms in these genes, the sequences of their promoter regions were screened in sickle cell anemia patients and correlated with both their HbF levels and their ÀS-globin haplotypes. Additionally, the sequences were compared with genes from 2 healthy groups, a reference one (N = 104) and an Afro-descendant one (N = 98), to identify polymorphisms linked to the ethnic background.The reference group was composed by healthy individuals from the general population. Four polymorphisms were identified in the promoter region of HBG2 and 8 in the promoter region of HBG1 among the studied groups. Four novel single nucleotide polymorphisms (SNP) located at positions -324, -317, -309 and -307 were identified in the reference group. A deletion located between -396 and -391 in the HBG2 promoter region and the SNP -271 C¨T in the HBG1 promoter region were associated with the Central African Republic ÀS-globin haplotype. In contrast, the -369 C¨G and 309 A¨G SNPs in the HBG2 promoter region were correlated to the Benin haplotype. The polymorphisms -396_-391 del HBG2, -369 SNP HBG2 and -271 SNP HBG1 correlated with HbF levels. Hence, we suggest an important role of HBG2 and HBG1 gene polymorphisms on the HbF synthesis.
Asunto(s)
Anciano , Niño , Femenino , Humanos , Masculino , Anemia de Células Falciformes/genética , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , gamma-Globinas/genética , Población Negra , Anemia de Células Falciformes/sangre , Brasil , Genotipo , HaplotiposRESUMEN
Fetal hemoglobin (HbF), encoded by the HBG2 and HBG1 genes, is the best-known genetic modulator of sickle cell anemia, varying dramatically in concentration in the blood of these patients. This variation is partially associated with polymorphisms located in the promoter region of the HBG2 and HBG1 genes. In order to explore known and unknown polymorphisms in these genes, the sequences of their promoter regions were screened in sickle cell anemia patients and correlated with both their HbF levels and their betaS-globin haplotypes. Additionally, the sequences were compared with genes from 2 healthy groups, a reference one (N = 104) and an Afro-descendant one (N = 98), to identify polymorphisms linked to the ethnic background.The reference group was composed by healthy individuals from the general population. Four polymorphisms were identified in the promoter region of HBG2 and 8 in the promoter region of HBG1 among the studied groups. Four novel single nucleotide polymorphisms (SNP) located at positions -324, -317, -309 and -307 were identified in the reference group. A deletion located between -396 and -391 in the HBG2 promoter region and the SNP -271 C-->T in the HBG1 promoter region were associated with the Central African Republic betaS-globin haplotype. In contrast, the -369 C-->G and 309 A-->G SNPs in the HBG2 promoter region were correlated to the Benin haplotype. The polymorphisms -396_-391 del HBG2, -369 SNP HBG2 and -271 SNP HBG1 correlated with HbF levels. Hence, we suggest an important role of HBG2 and HBG1 gene polymorphisms on the HbF synthesis.
Asunto(s)
Anemia de Células Falciformes/genética , Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , gamma-Globinas/genética , Anciano , Anemia de Células Falciformes/sangre , Población Negra , Brasil , Niño , Femenino , Genotipo , Haplotipos , Humanos , MasculinoRESUMEN
Glutathione S-transferase (GST) enzymes protect cells against xenobiotics and oxidative stress products through an electrophilic conjugation process. We investigated the theta (GSTT1) and mu (GSTM1) null genotypes in a group of leukopenic subjects and normal subjects from Northeast Brazil, evaluating their use as biomarkers of susceptibility for developing leukopenia. In a sample-based case-control study, we analysed white blood cell (WBC) counts and GSTT1 and GSTM1 genotypes. A total of 278 subjects were analysed: 91 with leukopenia and 187 controls. GSTT1 null genotype conferred a 5.92-fold risk for occurrence of leukopenia [odds ratios (OR) = 5.92, CI(MLE): 1.64-26.72, P(MLE) = 0.002] and a 3.90-fold risk of neutropenia (OR = 3.90; CI(MLE): 1.05-13.66; P(MLE) = 0.02), while GSTM1 null genotype conferred a 1.78-fold risk for leukopenia (OR = 1.75; CI(MLE): 1.04-3.06, P(MLE) = 0.017) and no risk of neutropenia (OR = 1.71; CI(MLE): 0.88-3.35; P(MLE) = 0.06). The GSTT1, but not the GSTM1 null genotype, was found to be associated with leukopenia and neutropenia. More cellular and molecular studies are needed to evaluate the existence of genotype interactions, and to confirm the appropriateness of using the GSTT1 and/or GSTM1 null genotypes as biomarkers of susceptibility to white blood-cell deficiencies.
Asunto(s)
Biomarcadores/sangre , Glutatión Transferasa/genética , Leucopenia/genética , Adulto , Brasil , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Genotipo , Humanos , MasculinoRESUMEN
The fetal hemoglobin (HbF) levels and betaS-globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Ggamma- and Agamma-globin gene promoters and the DNase I-2 hypersensitive sites in the locus control regions (HS2-LCR) of patients with HbF level disparities as compared to their betaS haplotypes. Sixty-four (51.2%) patients had CAR/Ben genotype; 36 (28.8%) Ben/Ben; 18 (14.4%) CAR/CAR; 2 (1.6%) CAR/Atypical; 2 (1.6%) Ben/Cam; 1 (0.8%) CAR/Cam; 1 (0.8%) CAR/Arab-Indian, and 1 (0.8%) Sen/Atypical. The HS2-LCR sequence analyses demonstrated a c.-10.677G>A change in patients with the Ben haplotype and high HbF levels. The Gg gene promoter sequence analyses showed a c.-157T>C substitution shared by all patients, and a c.-222_-225del related to the Cam haplotype. These results identify new polymorphisms in the HS2-LCR and Gg-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.
Asunto(s)
Anemia de Células Falciformes/genética , Desoxirribonucleasa I/genética , Globinas/genética , Región de Control de Posición/genética , Adulto , Niño , Preescolar , Hemoglobina Fetal/análisis , Marcadores Genéticos/genética , Genotipo , Haplotipos , Humanos , Persona de Mediana Edad , Regiones Promotoras Genéticas/genéticaRESUMEN
The fetal hemoglobin (HbF) levels and betaS-globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Gg- and Ag-globin gene promoters and the DNase I-2 hypersensitive sites in the locus control regions (HS2-LCR) of patients with HbF level disparities as compared to their ßS haplotypes. Sixty-four (51.2 percent) patients had CAR/Ben genotype; 36 (28.8 percent) Ben/Ben; 18 (14.4 percent) CAR/CAR; 2 (1.6 percent) CAR/Atypical; 2 (1.6 percent) Ben/Cam; 1 (0.8 percent) CAR/Cam; 1 (0.8 percent) CAR/Arab-Indian, and 1 (0.8 percent) Sen/Atypical. The HS2-LCR sequence analyses demonstrated a c.-10.677G>A change in patients with the Ben haplotype and high HbF levels. The Gg gene promoter sequence analyses showed a c.-157T>C substitution shared by all patients, and a c.-222_-225del related to the Cam haplotype. These results identify new polymorphisms in the HS2-LCR and Gg-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.
Asunto(s)
Adulto , Niño , Preescolar , Humanos , Persona de Mediana Edad , Anemia de Células Falciformes/genética , Desoxirribonucleasa I/genética , Globinas/genética , Región de Control de Posición/genética , Hemoglobina Fetal/análisis , Genotipo , Marcadores Genéticos/genética , Haplotipos , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: To determine folates, vitamin B12 and total homocysteine levels among neonates from mothers of low or high socioeconomic status. DESIGN: We carried out a cross-sectional transversal study comprising 143 neonates from two maternity hospitals in the city of Salvador, Northeast of Brazil. Cord blood samples were obtained at the time of delivery from newborns from low (group 1, n=77) or high (group 2, n=66) socioeconomic status. The vitamin B12 and folates were analyzed by electrochemiluminescence immunoassay and by a competitive test using a natural folate-binding protein (FBP), respectively. Total homocyteine levels were measured by fluorescence polarization immunoassay. Maternal environmental risk factors for pregnancy complications were obtained from all mothers. RESULTS: Only 2% of women from group 1 received prenatal care/vitamin supplementation, whereas almost all mothers from group 2 (96%) were properly followed. Anemia and/or infections pre- or during pregnancy was more prevalent among mothers of babies from group 1. Folate levels among newborns from group 1 and 2 were 7.38+/-2.71 and 8.83+/-4.06 ng/ml, respectively. No difference in the vitamin B12 levels was determined between groups. In addition, tHcy serum levels were higher among newborns from group 1 compared to those from group 2 (8.54+/-4.06 vs 6.35+/-1.33 micromol/l, respectively; P=0.005). CONCLUSION: These results demonstrate that unprivileged young woman has limited accesses to prenatal care, present high-risk factors that hamper both maternal and newborn health. Maternal and newborn health status could be improved by simply reinforcing the use of folate-enriched diet. The work presented illustrates the challenges that developing countries have to face in order to provide preventive adequate health care to the population at large.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/sangre , Recién Nacido/sangre , Vitamina B 12/sangre , Complejo Vitamínico B/sangre , Adulto , Estudios Transversales , Suplementos Dietéticos , Femenino , Sangre Fetal/química , Humanos , Masculino , Estado Nutricional , Embarazo , Atención Prenatal , Clase Social , Factores SocioeconómicosRESUMEN
Human herpesvirus 8 (HHV-8) seroprevalences were determined in two isolated Amazon Amerindian tribes, according to age, gender and familial aggregation. Plasma and serum samples obtained from 982 Amazon Amerindians (664 Tiriyó and 318 Waiampi) were tested for antibodies against lytic and latent HHV-8 antigens by using 'in-house' immunofluorescence assays. Overall, HHV-8 seroprevalence was 56.8 % (57.4 % in the Tiriyó tribe and 55.7 % in the Waiampi tribe). Seroprevalence was independent of gender and increased linearly with age: it was 35.0 % among children aged 2-9 years, 51.4 % in adolescents (10-19 years), 72.9 % in adults and 82.3 % in adults aged >50 years. Interestingly, 44.4 % of children under 2 years of age were HHV-8-seropositive. No significant differences in seroprevalence between tribes and age groups were detected. It is concluded that HHV-8 is hyperendemic in Brazilian Amazon Amerindians, with vertical and horizontal transmission during childhood, familial transmission and sexual contact in adulthood contributing to this high prevalence in these isolated populations.