RESUMO
We analyzed the influence of the season, the environment, and the sex, as well as the relation of body mass (BM) in the serum albumin (ALB), aspartate aminotransferase (AST), creatinine (C), creatine kinase (CK), phosphorus (P), total calcium (tCa), total protein (TP), urea (U), uric acid (UA), calcium:phosphorus ratio (Ca:P), and the globulin value (GV) of thirty individuals of Phrynops geoffroanus of the urban area of Cuiabá, Mato Grosso, Brazil. The modeling of biochemical parameters was performed using the Generalized Additive Models for Location, Scale and Shape (GAMLSS) to verify the influence of variables considered in this study on each of the biochemical parameters analyzed. The season influenced AST, CK, C, tCa, Ca:P and UA. The environment influenced tCa, Ca:P, U and UA. On the other hand, CK, tCa, P, Ca:P and U differed significantly between males and females. Regarding the BM, a relationship of this variable was observed with CK, C, tCa, P, U, UA and Ca:P. We concluded that the season, environment, sex, and body mass can influence the biochemical parameters of P. geoffroanus, and these factors should be routinely considered in the interpretation of laboratory results.
Analisou-se a influência da estação, do ambiente e do sexo, assim como a relação da massa corporal (BM) nos níveis sorológicos de albumina (ALB), aspartato aminotransferase (AST), creatinina (C), creatina quinase (CK), fósforo (P), cálcio total (tCa), sólidos totais (TS), ureia (U), ácido úrico (UA), relação cálcio:fósforo (Ca:P), e do valor da globulina (GV) de Phrynops geoffroanus da área urbana de Cuiabá, Mato Grosso, Brasil. A modelagem dos parâmetros bioquímicos foi realizada utilizando-se os modelos aditivos generalizados para locação, escala e forma (GAMLSS) para verificar a influência das variáveis consideradas neste estudo em cada um dos parâmetros bioquímicos analisados. A estação sazonal influenciou os níveis de AST, CK, C, tCa, Ca:P e UA. O ambiente foi capaz de influenciar tCa, Ca:P, U e UA. Por outro lado, CK, tCa, P, Ca:P e U diferiram significativamente entre machos e fêmeas. Em relação à BM, observou-se relação dessa variável com CK, C, tCa, P, U, UA e Ca:P. Concluiu-se que a estação sazonal, o ambiente, o sexo e a massa corporal são capazes de influenciar os parâmetros bioquímicos de P. geoffroanus e que esses fatores devem ser rotineiramente considerados na interpretação dos resultados laboratoriais.
Assuntos
Animais , Tartarugas/anatomia & histologia , Tartarugas/fisiologia , Índice de Massa Corporal , Soro/química , Análise Química do Sangue/veterináriaRESUMO
Turner syndrome (TS) is characterized by the presence of one full X chromosome and total or partial deletion of the second sex chromosome. Diagnosis of TS is often delayed, resulting in inappropriate treatment. Early diagnosis of TS using a neonatal screening test may improve preventive measures and treatment, thus improving patient quality of life. The goal of this study was to standardize a neonatal TS screening algorithm. Two study genes (ARSE and MAGEH1) and 1 normalizing gene (HBB) were used to detect the second X chromosome. We screened 996 newborns whose peripheral blood was collected and stored in filter paper. In addition, samples from 20 patients with confirmed diagnosis of TS were included in the study. Relative amounts of ARSE/HBB were determined using real-time polymerase chain reaction. The cutoff at the 5th percentile was arbitrarily set to indicate repetition of the test. The test was repeated in 51/1016 patients with ARSE/HBB < 0.81. For 10 samples with values persistently <0.81, we quantified the MAGEH1/HBB ratio. Values below the 95th percentile in TS patients (MAGEH1/HBB < 1.24) were considered to be inadequate. Only 6/996 NB showed inadequate values for the 2 studied genes, which were recalled for clinical evaluation and karyotype testing. Analysis of 20 patients diagnosed with TS allowed for identification of false-negatives and true-positives, establishing 95% sensitivity when the indicated cutoff values were used. In conclusion, our algorithm reached 95% detection sensitivity with an acceptable recall rate (0.6%), allowing for the detection of suspected TS cases in the neonatal period.
Assuntos
Arilsulfatases/genética , Testes Genéticos/métodos , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Síndrome de Turner/genética , Algoritmos , Feminino , Humanos , Recém-Nascido , Cariótipo , Cariotipagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA , Síndrome de Turner/diagnóstico , Globinas beta/genéticaRESUMO
Normal testosterone levels are frequently observed in women with androgenetic alopecia (AGA), suggesting the involvement of androgen sensitivity in this condition. Androgen sensitivity is related to androgen receptor (AR) messenger RNA (mRNA) production in hair follicles and is negatively related to the number of CAG repeats present in exon 1 of the AR gene. The aim of this study was to compare AR expression in AGA women with normal controls and to correlate this expression with the number of CAG repeats. Hair follicles were obtained from 27 women with AGA and 21 controls for AR gene expression analysis. AR expression was evaluated through AR mRNA quantification using real-time polymerase chain reaction and the number of CAG repeats in the AR gene was determined in complementary DNA samples obtained from hair follicles and analyzed with the Gene Scan software. AR mRNA in the frontal-parietal region was significantly higher than in the occipital region of AGA patients (paired t-test, P = 0.046). No significant difference was identified in controls (P = 0.67). Both regions in the same individual showed a significant positive correlation in AGA patients (r = 0.77; P < 0.05) and in controls (r = 0.91; P < 0.05). A negative correlation was identified between AR expression and the number of CAG repeats only in AGA patients (r = 0.510; P = 0.013). The identification of elevated AR mRNA quantitation in hair follicles is a useful tool for identifying potentially abnormal androgen sensitivity in AGA patients.
Assuntos
Alopecia/genética , Folículo Piloso/metabolismo , Receptores Androgênicos/genética , Adulto , Idoso , Alelos , DNA Complementar/genética , Éxons/genética , Feminino , Regulação da Expressão Gênica , Técnicas de Genotipagem , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Expansão das Repetições de Trinucleotídeos/genética , Adulto JovemRESUMO
Insulin resistance is an underlying cause of metabolic changes associated with cardiovascular diseases. Glucocorticoids are known determinant factors of insulin resistance. We quantified glucocorticoid receptor alpha (GRα) mRNA and 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) mRNA in various tissues of 35 patients with previously established cardiovascular disease. This was a prospective study in a cardiac surgery patient setting. Samples of subcutaneous adipose tissue, epicardial fat, muscle, and peripheral blood mononuclear cells were examined. GRα and 11ß-HSD1 mRNA were determined by real-time PCR. Mean age was 54.4 years. A significantly higher level of GRα mRNA was observed in muscle, with mean = 43.6 arbitrary units, median (p25-p75) = 39.4, compared to epicardial adipose tissue, with mean = 34.2, median (p25-p75) = 27.6, and to subcutaneous adipose tissue, with mean = 29.0, median (p25-p75) = 19.0, and lymphocytes, with mean = 17.5, median (p25-p75) = 14.02. When patients with diabetes mellitus were compared to patients without insulin resistance, significantly lower levels of GRα mRNA were observed in epicardial fat. Lymphocytes had the lowest 11ß-HSD1 mRNA concentration. We also observed significantly reduced 11ß-HSD1 mRNA levels in visceral fat when compared with muscle tissue. GRα and 11ß-HSD1 mRNA levels differed among tissues involved in the pathophysiology of metabolic syndrome. We conclude that epicardial adipose tissue has lower GRαmRNA levels in insulin-resistant patients; this seems to be an adaptive and protective mechanism.
Assuntos
Adaptação Fisiológica/genética , Resistência à Insulina/genética , Especificidade de Órgãos/genética , Receptores de Glucocorticoides/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/cirurgia , Feminino , Regulação da Expressão Gênica , Humanos , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , Pericárdio/patologia , Pericárdio/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/metabolismoRESUMO
The glutathione S-transferase (GST) family consists of phase II detoxification enzymes that catalyze the conjugation of toxic substances, such as chemotherapeutic agents, to glutathione. We examined whether GSTT1/GSTT1"null", GSTM1/GSTM1"null" and GSTP1Ile105Ile/GSTP1Ile105Val polymorphisms are associated with different response rates to neoadjuvant chemotherapy in the treatment of stage II and III breast cancer. Forty Brazilian women with invasive ductal adenocarcinoma of the breast submitted to neoadjuvant chemotherapy, using 5-fluorouracil, epirubicin and cyclophosphamide, were genotyped for the GSTT1, GSTM1 and GSTP1 genes. Clinical response was assessed by RECIST criteria. Comparisons were made for the three genes alone and in pairs, as polymorphic and as wild-type combinations and polymorphic/wild-type combinations. We analyzed all possible combinations and their response rate. Patients with the GSTT1/GSTP1105Ile combination were found to have a significantly better response than GSTT1"null"/GSTP1105Val (P = 0.0209) and GSTT1/GSTM1 (P = 0.0376) combinations. Analysis of all possible combinations showed the GSTM1"null" polymorphic genotype to be present in four, and the wild-type GSTP1105Ile in six of the combinations associated with the largest number of responding patients. We found that patients with the GSTT1/GSTP1105Ile wild-type combination had a significantly higher response rate to chemotherapy than patients with the respective polymorphic GSTT1"null"/GSTP1105Val combination or patients with the wild-type GSTT1/GSTM1. The six gene combinations associated with the largest number of responding patients were found to contain the wild-type GSTP1105Ile and the polymorphic-type GSTM1"null". These specific combinations were virtually absent in the combinations with few responding patients.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Idoso , Brasil , Neoplasias da Mama/enzimologia , Carcinoma Ductal de Mama/genética , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Glutationa/metabolismo , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Turner syndrome (TS) is the complete or partial loss of the second sex chromosome, occurring in 1:5 000 girls. Early recognition allows appropriate therapy for short stature and puberty. Neonatal diagnosis of TS permits detection of associated malformations, minimizing sequels. Aiming to develop a molecular method for the diagnosis of TS we employed blood samples stored on filter paper. We evaluated 78 female controls, 25 TS girls with 45,X karyotype, and 32 TS patients with other karyotypes. After DNA extraction, samples were submitted to real-time PCR, using primers and probes directed to the study gene ARSE and to the control gene GAPDH. A ROC curve established the ARSE:GAPDH ratio with a cutoff value of 0.7. Low ARSE:GAPDH ratio of <0.7 was present in 100% of 45,X TS patients. This cutoff value presented a sensitivity of 100% and a specificity of 100% in detecting 45,X TS patients with a positive predictive value of 100% and a negative predictive value of 100%. The same cutoff value was able to identify only 56% of TS with other karyotypes, in which we observed a mean (SD) ARSE:GAPDH ratio=0.66 (0.2); and the interquartile range=0.4-0.8. Determination of ARSE:GAPDH ratio is a fast, sensitive, and specific method, with viable cost and feasible automation, which makes it potentially applicable in neonatal screening programs for the diagnosis of Turner syndrome 45,X.
Assuntos
Triagem Neonatal/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Arilsulfatases/genética , Estudos de Casos e Controles , Dosagem de Genes/genética , Humanos , Recém-Nascido , CariotipagemRESUMO
BACKGROUND/AIMS: While laboratory methods for the detection of testicular tissue are well standardized, currently there is no available test to demonstrate the presence of ovarian tissue. We evaluated the effectiveness of gonadal stimulation with luteinizing hormone (LH)/follicle-stimulating hormone (FSH) for the detection of ovarian tissue in patients with disorders of sex development (DSD). METHODS: Ten patients with congenital adrenal hyperplasia (CAH) as ovarian-positive controls, 10 with cryptorchidism (ovarian-negative controls), 13 patients with DSD of no defined etiology and 7 patients with ovotesticular DSD (true hermaphroditism, TH) were included in the study. They underwent a daily injection of both LH and FSH on 3 consecutive days. LH, FSH, estradiol, testosterone and inhibin A were measured before treatment, 24 h after the 1st dose and 24 h after the 3rd dose. RESULTS: Estradiol increased in all CAH and TH patients, with a median value of 155.1 and 92.6 pg/ml, respectively, after the 3rd injection. Inhibin A also increased in all CAH and TH patients, with a median value of 70.4 and 32.2 pg/ml, respectively, after the 3rd injection. There was no change in these hormones in the other groups. CONCLUSION: The LH/FSH stimulation test might be a useful method to detect the presence of ovarian tissue.
Assuntos
Transtornos do Desenvolvimento Sexual/sangue , Hormônio Foliculoestimulante/administração & dosagem , Hormônios/administração & dosagem , Inibinas/sangue , Hormônio Luteinizante/administração & dosagem , Ovário , Adolescente , Criança , Pré-Escolar , Estradiol/sangue , Feminino , Humanos , Lactente , MasculinoRESUMO
The activity of the hypothalamic-pituitary-adrenal axis is usually modulated by several stress factors, including exercise. Different responses are induced by physical training according to duration and intensity of exercise. During prolonged training, cortisol remains normal or decreased as a consequence of altered cortisol secretion, metabolism and excretion, and possibly by changes in glucocorticoid sensitivity. The aim of this study was to evaluate the impact of prolonged physical training on the glucocorticoid sensitivity. Eighteen cadets of the Air Force Academy, mean (SD) age: 18.7 (1.0) years, underwent an intensive 6-week preparatory training-period considered adequate by inducing significant changes on body composition measured by bioelectrical impedance. Measurement of individual's pituitary glucocorticoid sensitivity was done by an intravenous very low dose dexamethasone suppression test (20 microg/m (2)) that was performed before and after the training period. Cortisol levels were obtained at basal condition and 120 minutes after the dexamethasone infusion. Basal cortisol showed a significant decrease after prolonged training. The percent cortisol suppression after dexamethasone tended to be lower after the training period. Overall, our data suggest that prolonged physical training is able to reduce glucocorticoid sensitivity, which can have a beneficial impact in chronic stress conditions.
Assuntos
Dexametasona/administração & dosagem , Dexametasona/farmacologia , Exercício Físico/fisiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Hipófise/efeitos dos fármacos , Adolescente , Adulto , Antropometria , Composição Corporal/efeitos dos fármacos , Brasil , Relação Dose-Resposta a Droga , Impedância Elétrica , Humanos , Hidrocortisona/sangue , Injeções Intravenosas , Masculino , MilitaresRESUMO
Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients' medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was able to detect all cases of TS 45,X and the majority of mosaicisms, without the need for more X chromosome markers. In conclusion, determining the number of CAG repeats of the androgen receptor gene analyzed by GeneScan was a fast method with high sensitivity for the detection of TS 45,X, suggesting that it could be interesting as a method for screening a population of growth-retarded girls.
Assuntos
Estatura/genética , Éxons , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Síndrome de Turner/diagnóstico , Alelos , Criança , Feminino , Marcadores Genéticos , Heterozigoto , Homozigoto , Humanos , Cariotipagem , Mosaicismo , Sensibilidade e Especificidade , Estatística como Assunto , Fatores de TempoRESUMO
Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was...