RESUMO
BACKGROUND: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF). OBJECTIVE: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain). METHODS: BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9-11 years, normalized by creatinine and log-2 transformed. At adolescence (15-17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit. RESULTS: Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (ß = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (ß = 0.80; 95% CI: -0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (ß = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (ß = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend ≤ 0.01), and CpG6-thought problems (p-trend ≤ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (ß = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association. CONCLUSIONS: In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior relationships previously described in the epidemiological literature. Given its novelty and preliminary nature, this effect biomarker approach should be replicated in larger birth cohorts.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Exposição Ambiental , Adolescente , Compostos Benzidrílicos , Criança , Cromatografia Líquida , Exposição Ambiental/análise , Humanos , Masculino , Fenóis , Estudos Prospectivos , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Childhood obesity is one of the most serious public health challenges of our times. Although an important body of experimental evidence highlights the obesogenic potential of endocrine disruptors such as bisphenol A (BPA), the epidemiological evidence remains inconclusive and limited. OBJECTIVE: To assess associations between urinary BPA concentrations and several adiposity measures in peripubertal boys from the Environment and Childhood (INMA) cohort in Granada, Spain. MATERIAL AND METHODS: BPA concentrations were determined in spot urine samples from 298 boys aged 9-11, and their weight, height, waist circumference, and percentage body fat mass were measured. Overweight/obesity was defined as BMI z-score ≥85th percentile and abdominal obesity as waist-to-height ratio (WHtR) ≥0.5. Associations were assessed using multivariable linear and logistic regression models. RESULTS: In adjusted models, each natural log-unit increase in urinary BPA concentrations was associated with higher BMI z-score (ßâ¯=â¯0.22; 95%CIâ¯=â¯0.03, 0.41) and increased odds of overweight/obesity (ORâ¯=â¯1.46; 95%CIâ¯=â¯1.05, 2.05). Children with higher BPA concentrations had higher WHtR values (ßâ¯=â¯0.007; 95%CIâ¯=â¯-0.001, 0.015), and BPA was associated with a greater risk of abdominal obesity (ORâ¯=â¯1.45; 95%CIâ¯=â¯1.03, 2.06). No associations were found with % body fat mass. CONCLUSIONS: BPA may exert an obesogenic effect in peripubertal boys, potentially increasing the risk of overweight/obesity, especially abdominal obesity. However, these results should be interpreted with caution given the modest sample size and the possibilities of reverse causality and residual confounding by diet and lifestyle patterns.
Assuntos
Adiposidade , Compostos Benzidrílicos , Exposição Ambiental/estatística & dados numéricos , Fenóis , Índice de Massa Corporal , Criança , Estudos Transversais , Humanos , Masculino , Espanha , Circunferência da CinturaRESUMO
INTRODUCTION: Bisphenol A (BPA) is a well-known endocrine disrupting compound. Although several studies have investigated the effect of BPA exposure and reproductive hormones in humans, results have been inconsistent. OBJECTIVE: To explore the cross-sectional relationship between bisphenol A (BPA) exposure and reproductive hormones/cortisol among peripubertal boys. MATERIAL AND METHODS: Urinary BPA and serum hormones were assessed in 172 boys belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11years of age. BPA concentrations were quantified by liquid chromatography-mass spectrometry, and levels of serum total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol were measured by electrochemiluminescence immunoassay. RESULT(S): After adjustment for confounders, linear regression models showed that each natural-log unit increase in urinary BPA concentrations was associated with a 19% increase in geometric mean (GM) serum TT levels, and a 16% decrease in GM serum cortisol levels. When urinary BPA concentrations were categorized in tertiles, boys in the 3rd tertile showed 49% higher TT levels and 23% lower cortisol concentrations compared to boys in the 1st tertile. Additionally, urinary BPA concentrations were also significantly associated with higher TT:LH and TT:cortisol ratios, but not with serum LH or FSH levels. CONCLUSION(S): Our results suggest the possible endocrine disrupting potential of BPA during this important period of development. Although action at the testis or pituitary cannot be ruled out, our findings are compatible with a possible involvement of BPA at the adrenal gland, resulting in a differential production of androgens/cortisol. However, given the cross-sectional design of our study, the heterogeneous results reported in the literature, and the scant experimental research on BPA effects at the adrenal gland, the present findings should be interpreted with caution.
Assuntos
Compostos Benzidrílicos/urina , Hormônio Foliculoestimulante/sangue , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Fenóis/urina , Testosterona/sangue , Glândulas Suprarrenais/efeitos dos fármacos , Criança , Estudos Transversais , Exposição Ambiental/análise , Humanos , Masculino , EspanhaRESUMO
Invertase immobilized on magnetic diatomaceous earth nanoparticles (mDE-APTES-invertase) with high sucrolytic activity was obtained by an easy and low-cost method. An experimental design was carried out to investigate the best immobilization conditions and it allowed obtaining an immobilized derivative with a residual specific activity equal to 92.5%. Then, a second experimental design selected the mDE-APTES-invertase with higher specific activity in relation to other derivatives reported in the literature (2.42-fold). Thermal and storage stability for immobilized invertase were found to be 35 °C for 60 min (85% retained activity) and 120 days storage period (80% retained activity), respectively. Besides, a residual activity higher than 60% and 50% were observed for mDE-APTES-invertase after reuse in short and long term, respectively. Given the simple and efficient method to obtain an immobilized derivative with high activity, the mDE nanoparticles appear to be a promising matrix for invertase immobilization as well as for other biomolecules.
RESUMO
α-L-rhamnosidase from Aspergillus terreus was covalently immobilized on the following ferromagnetic supports: polyethylene terephthalate (Dacron-hydrazide), polysiloxane/polyvinyl alcohol (POS/PVA), and chitosan. The powdered supports were magnetized by thermal coprecipitation method using ferric and ferrous chlorides, and the immobilization was carried out via glutaraldehyde. The activity of the Dacron-hydrazide (0.53 nkat/µg of protein) and POS/PVA (0.59 nkat/µg of protein) immobilized enzyme was significantly higher than that found for the chitosan derivative (0.06 nkat/µg of protein). The activity-pH and activity-temperature profiles for all immobilized enzymes did not show difference compared to the free enzyme, except the chitosan derivative that presented higher maximum temperature at 65 °C. The Dacron-hydrazide derivative thermal stability showed a similar behavior of the free enzyme in the temperature range of 40-70 °C. The POS/PVA and chitosan derivatives were stable up to 60 °C, but were completely inactivated at 70 °C. The activity of the preparations did not appreciably decrease after ten successive reuses. Apparent K (m) of α-L-rhamnosidase immobilized on magnetized Dacron-hydrazide (1.05 ± 0.22 mM), POS/PVA (0.57 ± 0.09 mM), and chitosan (1.78 ± 0.24 mM) were higher than that estimated for the soluble enzyme (0.30 ± 0.03 mM). The Dacron-hydrazide enzyme derivative showed better performance than the free enzyme to hydrolyze 0.3% narigin (91% and 73% after 1 h, respectively) and synthesize rhamnosides (0.116 and 0.014 mg narirutin after 1 h, respectively).
Assuntos
Aspergillus/enzimologia , Biotecnologia/métodos , Enzimas Imobilizadas/metabolismo , Glicosídeo Hidrolases/metabolismo , Imãs , Quitosana/química , Estabilidade Enzimática , Flavanonas/metabolismo , Glicosídeo Hidrolases/química , Concentração de Íons de Hidrogênio , Cinética , Polietilenotereftalatos/química , Álcool de Polivinil/química , Ramnose/metabolismo , Siloxanas/química , TemperaturaRESUMO
The kinetics of thermal inactivation of A. terreus alpha-rhamnosidase was studied using the substrate p-nitrophenyl alpha-L-rhamnoside between 50 degrees C and 70 degrees C. Up to 60 degrees C the inactivation of the purified enzyme was completely reversible, but samples of crude or partially purified enzyme showed partial reversibility. The presence of the product rhamnose, the substrate naringin, and other additives reduced the reversible inactivation, maintaining in some cases full enzyme activity at 60 degrees C. A mechanism for the inactivation process, which permitted the reproduction of experimental results, was proposed. The products rhamnose (inhibition constant, 2.1 mM) and prunin (2.6 mM) competitively inhibited the enzyme reaction. The maximum hydrolysis of supersaturated naringin solution, without enzyme inactivation, was observed at 60 degrees C. Hydrolysis of naringin reached 99% with 1% naringin solution, although the hydrolysis degree of naringin was only 40% due to products inhibition when the initial concentration of flavonoid was 10%. The experimental results fitted an equation based on the integrated Michaelis-Menten's, including competitive inhibition by products satisfactorily.
Assuntos
Aspergillus/efeitos dos fármacos , Flavanonas , Flavonoides/metabolismo , Glicosídeo Hidrolases/antagonistas & inibidores , Proteínas de Plantas , Algoritmos , Aspergillus/enzimologia , Reagentes de Ligações Cruzadas , Meios de Cultura , Globulinas/farmacologia , Temperatura Alta , Hidrólise , Cinética , TemperaturaRESUMO
1) Se considera a la operación de Heller como el tratamiento de elección en el megaesófago funcional, que generalmente corresponde con los grados I y II. 2) En el reducido grupo de grandes megaesófagos (grado III y formas recidivadas), por lo general de larga evolución y con participación "orgánica", aconsejamos como operación primaria la interposición esófago gástrica de un asa yeyunal pediculada. 3) Si bien nuestra experiencia es muy reducida, no hemos obtenido con la "dilatación forzada" los éxitos que algunos autores proclaman y estamos lejos de otorgarle un lugar prioritario, en razón de lo aleatorio de los resultados y porque no se halla exenta de riesgos. 4) Encontramos en la dilatación periódica y permanente con bujías de mercurio, un recurso paliativo a tener muy en cuenta, tanto por sus resultados aceptables como por la benignidad del procedimiento
Assuntos
Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Acalasia Esofágica/cirurgia , DilataçãoRESUMO
En los últimos 9 años fueron tratados quirúrgicamente, por cáncer de colon 67 pacientes. De esta experiencia, los autores extraen los principios de técnica aplicados para cada uno de los segmentos colónicos involucrados
Assuntos
Humanos , Neoplasias do Colo/cirurgiaRESUMO
1) Se considera a la operación de Heller como el tratamiento de elección en el megaesófago funcional, que generalmente corresponde con los grados I y II. 2) En el reducido grupo de grandes megaesófagos (grado III y formas recidivadas), por lo general de larga evolución y con participación "orgánica", aconsejamos como operación primaria la interposición esófago gástrica de un asa yeyunal pediculada. 3) Si bien nuestra experiencia es muy reducida, no hemos obtenido con la "dilatación forzada" los éxitos que algunos autores proclaman y estamos lejos de otorgarle un lugar prioritario, en razón de lo aleatorio de los resultados y porque no se halla exenta de riesgos. 4) Encontramos en la dilatación periódica y permanente con bujías de mercurio, un recurso paliativo a tener muy en cuenta, tanto por sus resultados aceptables como por la benignidad del procedimiento (AU)
Assuntos
Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Humanos , Masculino , Feminino , Acalasia Esofágica/cirurgia , DilataçãoRESUMO
En los últimos 9 años fueron tratados quirúrgicamente, por cáncer de colon 67 pacientes. De esta experiencia, los autores extraen los principios de técnica aplicados para cada uno de los segmentos colónicos involucrados (AU)