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INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 3% of children in the world. OBJECTIVE: In this work, we seek to compare the different brain activations of pediatric patients with and without ADHD. METHODS: A functional resonance examination with BOLD contrast was applied using the MOXO-CPT test (Continuous Performance test with single and double visual-auditory distractors). RESULTS: Differences in BOLD activation were observed indicating that control children regularly presented negative BOLD activations that were not found in children with ADHD. Inhibitory activity in audiovisual association zones in control patients was greater than in patients with ADHD. The inhibition in the frontal and motor regions in the controls contrasted with the overactivation of the motor areas in patients with ADHD, this, together with the detection of cerebellar activation which attempted to modulate the responses of the different areas that lead to executive failure in patients with ADHD. CONCLUSIONS: In view of these results, it can be argued that the lack of inhibition of ADHD patients in their executive functions led to a disorganization of the different brain systems.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Córtex Motor , Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Encéfalo , Função Executiva , Cerebelo , Imageamento por Ressonância MagnéticaRESUMO
The energy stored in fatty acids is essential for several critical activities of insects, such as embryogenesis, oviposition, and flight. Rhodnius prolixus is an obligatory hematophagous hemipteran and vector of Chagas disease, and it feeds infrequently on very large blood meals. As digestion slowly occurs, lipids are synthesized and accumulate in the fat body, mainly as triacylglycerol, in lipid droplets. Between feeding bouts, proper mobilization and oxidation of stored lipids are crucial for survival, and released fatty acids are oxidized by mitochondrial ß-oxidation. Carnitine palmitoyl transferase I (CPT1) is the enzyme that catalyzes the first reaction of the carnitine shuttle, where the activated fatty acid, acyl-CoA, is converted to acyl-carnitine to be transported into the mitochondria. Here, we investigated the role of CPT1 in lipid metabolism and in resistance to starvation in Rhodnius prolixus. The expression of the CPT1 gene (RhoprCpt1) was determined in the organs of adult females on the fourth day after a blood meal, and the flight muscle showed higher expression levels than the ovary, fat body, and anterior and posterior midgut. RhoprCpt1 expression in the fat body dramatically decreased after feeding, and started to increase again 10 days later, but no changes were observed in the flight muscle. ß-oxidation rates were determined in flight muscle and fat body homogenates with the use of 3H-palmitate, and in unfed females, they were higher in the flight muscle. In the fat body, lipid oxidation activity did not show any variation before or at different days after feeding, and was not affected by the presence of etomoxir or malonyl-CoA. We used RNAi and generated RhoprCPT1-deficient insects, which surprisingly did not show a decrease in measured 3H-palmitate oxidation rates. However, the RNAi-knockdown females presented increased amounts of triacylglycerol and larger lipid droplets in the fat body, but not in the flight muscle. When subjected to starvation, these insects had a shorter lifespan. These results indicated that the inhibition of RhoprCpt1 expression compromised lipid mobilization and affected resistance to starvation.
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Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
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El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.
The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.
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Animais , Masculino , Camundongos , Dieta/efeitos adversos , Exenatida/administração & dosagem , Obesidade/etiologia , Obesidade/metabolismo , Oxirredução , Western Blotting , Músculo Esquelético/metabolismo , Termogênese , Ácidos Graxos/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Proteína Desacopladora 2 , Irinotecano , Injeções Intraperitoneais , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) has mandated all hospitals to publish the charges of 300 common procedures to provide price transparency. The aims of our study are to evaluate 50 top orthopedic hospitals to determine compliance with this mandate and to assess the ease of finding cost information for arthroplasty procedures. METHODS: The websites of the top 50 US News and World Report (USNWR) orthopedic hospitals were searched to find publicly accessible procedural charges. Data included the number of clicks to locate pricing documents, number of files provided, and number of data rows pertaining to arthroplasty. Charge data was queried based on Diagnosis related group (DRG) codes (469, 470), Current Procedural Technology (CPT) codes (27130, 27477), and keyword searches ("arthroplasty", "total hip", and "total knee"). RESULTS: Forty-four (88%) of the top 50 USNWR Orthopedic institutions had publicly accessible files containing cost information. Thirty three of the 44 institutions provided results with DRG search while less than 10 institutions used CPT and keyword searches. There was an average of 226,190 (range 304-1,121,876) rows of data per file. Average charges varied depending on the use of DRG, CPT or keyword searches ($6,663-$117,072). CONCLUSION: The majority of compliant hospitals published large data files requiring the use of DRG codes to find cost information with extreme variation in resultant charges provided. These findings underscore the lack of direct patient benefit afforded by the current mandate, as pricing determinations require expert knowledge in medical coding and have a high variability in the reported charges.
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Artroplastia de Quadril , Artroplastia do Joelho , Efeitos Psicossociais da Doença , Ortopedia , Idoso , Artroplastia de Quadril/economia , Artroplastia do Joelho/economia , Hospitais , Humanos , Medicare , Estados UnidosRESUMO
Lipid metabolism dysfunction is closely related to obesity, inflammation, diabetes, lipodystrophy, cardiovascular disease. Along with having a positive effect on energy homeostasis during fasting or prolonged exercise through mitochondrial fatty acid oxidation (FAO), more than two dozen enzymes and transport proteins are involved in the activation and transport of fatty acids into the mitochondrial, providing insights into their critical roles in metabolism. CPT1A has been reported to be expressed ubiquitously in the body and associated with dire consequences affecting fat deposition as the key rate-limiting enzyme of FAO. However, there is a dearth of data on the specific role of CPT1A on adipogenic differentiation and adipocyte lipolysis on chicken. This study assessed CPT1A's function in adipocyte differentiation andadipocyte lipolysis, and the mechanisms were investigated. We found that CPT1A knockdown (KD) promotes the differentiation of chicken preadipocytes into mature adipocytes. CPT1A KD increased PPARγ protein expression level. Expression levels of lipid synthesis-related genes were increased, and lipolysis genes were reduced. Also, CPT1A KD can encourage the formation of lipid droplets. So our results confirmed that knockdown of CPT1A induced the lipid differentiation and inhibited the ß-oxidation process to promote the formation of lipid droplets. These findings may deepen our understanding on CPT1A function, especially its regulatory role in adipocyte biology.(AU)
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Animais , Carnitina O-Palmitoiltransferase , Galinhas/fisiologia , Adipócitos/classificação , Metabolismo dos Lipídeos , Técnicas de Silenciamento de Genes/instrumentaçãoRESUMO
Objetivo: Comparar la salud periodontal de embaraza- das y no embarazadas mediante la aplicación del Índice de Periodontal Comunitario (IPC). Materiales y métodos: Se realizó un estudio ob- servacional de corte transversal. Se reclutaron 100 mujeres embarazadas (EMB) y 50 no embarazadas (NoEMB) que concurrieron al Hospital Materno Provincial de la Ciudad de Córdoba, Dr. Raúl F. Lucini. En todas se registró el IPC con la sonda periodontal WHO 621 en los 6 sextantes de la boca. Los datos se analizaron con el software Infostat/SP; el nivel de significación establecido fue de P <0,05. Resultados: El 70% de las pacientes presentó edades de entre 18 y 25 años. En las EMB el código 3 del IPC fue el más frecuente presente en 240 sextantes (40,1%) y en las NoEMB el código 2 fue el más frecuente con 39 sextantes (43%). A ambos grupos de estudio les corresponde el trata- miento de instrucción de higiene bucal, instrumentación supra y/o subgingival, y/o regularización de obturaciones. Conclusiones: El código 3 fue el más frecuente entre las EMB, a quienes les corresponde un Código de tratamiento periodontal (CTP) 2; las NoEMB presentaron un IPC de 1 y 2 como los más frecuentes y se vinculan con un CTP 1 y 2. Nos encontramos frente a una situación clínica periodontal posible de resolver con terapia básica que puede ser realizada por odontólogos generalistas (AU)
Aim: To compare the periodontal health of pregnant and non-pregnant women by applying the Community Periodontal Index (CPI). Materials and methods: In an observational, cross-sec- tional study, 100 pregnant women (PREG) and 50 non-preg- nant women (NonPREG) were recruited at the Dr. Raúl F. Lu- cini Provincial Maternity Hospital in Córdoba City. The CPI was determined in the 6 sextants of the mouth using a WHO 621 periodontal probe. The data were analyzed with Infostat SP software. P <0.05 was considered significant. Results: 70% of the patients were 18 to 25 years old. In the PREG group, CPI Code 3 was the most frequent, present in 240 sextants (40.1%), while in the non-PREG group, CPI Code 2 was the most frequent, with 39 sextants (43%). Treat- ment needs in both study groups are oral hygiene instruction, supra- and/or subgingival instrumentation, and/or correction of plaque retentive margins. Conclusions: Code 3 was the most frequent among preg- nant women, which corresponded to Periodontal Treatment Code (CTP) 2. CPI 1 and 2 were the most frequent in non-pregnant women, corresponding to CTP 1 and 2. This periodontal clinical condition can be treated with initial dental hygiene therapy, which can be performed by general dentists (AU)
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Humanos , Feminino , Gravidez , Adolescente , Adulto , Adulto Jovem , Doenças Periodontais/epidemiologia , Complicações na Gravidez/epidemiologia , Índice Periodontal , Saúde Bucal , Necessidades e Demandas de Serviços de Saúde , Higiene Bucal/educação , Argentina/epidemiologia , Estudos Transversais , Promoção da SaúdeRESUMO
Objective: Continuous performance tests (CPTs) usually utilize visual stimuli. A previous investigation showed that inattention is partially independent of modality, but response inhibition is modality-specific. Here we aimed to compare performance on visual and auditory CPTs in ADHD and in healthy controls. Method: The sample consisted of 160 elementary and high school students (43 ADHD, 117 controls). For each sensory modality, five variables were extracted: commission errors (CEs) and omission errors (OEs), reaction time (RT), variability of reaction time (VRT), and coefficient of variability (CofV = VRT / RT). Results: The ADHD group exhibited higher rates for all test variables. The discriminant analysis indicated that auditory OE was the most reliable variable for discriminating between groups, followed by visual CE, auditory CE, and auditory CofV. Discriminant equation classified ADHD with 76.3% accuracy. Conclusion: Auditory parameters in the inattention domain (OE and VRT) can discriminate ADHD from controls. For the hyperactive/impulsive domain (CE), the two modalities are equally important.
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Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Humanos , Comportamento Impulsivo , Testes Neuropsicológicos , Tempo de ReaçãoRESUMO
A atenção sustentada é um domínio cognitivo presente em atividades essenciais na rotina de jovens universitários que dispendem muitas horas em sala de aula, concentrando a atenção em aulas expositivas, realização de exercícios e estudos para provas. Este estudo investigou a relação entre a prática regular com videogames e a habilidade de atenção sustentada avaliada através do CPT II. Colaboraram com a pesquisa 122 universitários da região metropolitana de Florianópolis, divididos entre jogadores de videogame de ação e não ação, bem como não jogadores. Os participantes responderam uma bateria de testes, incluindo a avaliação da atenção sustentada, mapeamento de dados sociodemográficos e hábitos com videogames. Os resultados demonstram que, ao controlar o impacto de variáveis intervenientes, não se constatou diferença atencional entre os grupos. A comparação entre sexos apresentou significância com relação ao desempenho atencional, em que os homens tendem a responder mais rápido e mulheres cometem menos erros. Os achados sugerem que a prática regular com videogames não possui relação com desempenho atencional e pesquisas futuras devem investigar impactos de variáveis intervenientes, como a comparação entre sexos.
Sustained attention is a cognitive domain present in essential activities in the routine of young university students who spend many hours in the classroom, focusing attention on lectures, performing exercises and studying for tests. This study investigated the relationship between regular practice with video games and the sustained attention skill assessed through CPT II. 122 university students from the metropolitan region of Florianópolis collaborated with the research, divided between action and non-action video game players, as well as non-players. Participants performed a battery of tests, including the assessment of sustained attention, mapping of sociodemographic data and habits with video games. The results demonstrate that, when controlling the impact of intervening variables, there was no attentional difference between the groups. The comparison between sexes was significant in terms of attentional performance, in which men tend to respond faster and women make fewer mistakes. The findings suggest that regular practice with video games is not related to attentional performance and future research should investigate the impacts of intervening variables, such as such as sex comparison.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Atenção , Jogos de VídeoRESUMO
Triple-negative breast cancers (TNBCs) lack progesterone and estrogen receptors and do not have amplified human epidermal growth factor receptor 2, the main therapeutic targets for managing breast cancer. TNBCs have an altered metabolism, including an increased Warburg effect and glutamine dependence, making the glutaminase inhibitor CB-839 therapeutically promising for this tumor type. Accordingly, CB-839 is currently in phase I/II clinical trials. However, not all TNBCs respond to CB-839 treatment, and the tumor resistance mechanism is not yet fully understood. Here we classified cell lines as CB-839-sensitive or -resistant according to their growth responses to CB-839. Compared with sensitive cells, resistant cells were less glutaminolytic and, upon CB-839 treatment, exhibited a smaller decrease in ATP content and less mitochondrial fragmentation, an indicator of poor mitochondrial health. Transcriptional analyses revealed that the expression levels of genes linked to lipid metabolism were altered between sensitive and resistant cells and between breast cancer tissues (available from The Cancer Genome Atlas project) with low versus high glutaminase (GLS) gene expression. Of note, CB-839-resistant TNBC cells had increased carnitine palmitoyltransferase 2 (CPT2) protein and CPT1 activity levels. In agreement, CB-839-resistant TNBC cells mobilized more fatty acids into mitochondria for oxidation, which responded to AMP-activated protein kinase and acetyl-CoA carboxylase signaling. Moreover, chemical inhibition of both glutaminase and CPT1 decreased cell proliferation and migration of CB-839-resistant cells compared with single inhibition of each enzyme. We propose that dual targeting of glutaminase and CPT1 activities may have therapeutic relevance for managing CB-839-resistant tumors.
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Benzenoacetamidas/farmacologia , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glutaminase/antagonistas & inibidores , Glutamina/metabolismo , Tiadiazóis/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Feminino , Humanos , Oxirredução , Neoplasias de Mama Triplo Negativas/enzimologia , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais CultivadasRESUMO
Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.
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Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Dislipidemias/prevenção & controle , Óleos de Peixe/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Animais , Dislipidemias/etiologia , Ácidos Graxos Ômega-3/metabolismo , Feminino , Gordura Intra-Abdominal/metabolismo , Leptina/sangue , Fígado/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Wistar , Triglicerídeos/metabolismoRESUMO
Data regarding clinical and neuropsychological features of attention deficit in children with lower cognitive ability is still scarce. The objective was to analyze the response patterns on the Continuous Performance Test II in children with Intellectual Disability and Attention Defficit Hyperactivity Disorder (ADHD). This is a cross-sectional study, in which patients were divided into 2 groups: one group with ADHD and Full IQ > 80 and another group with ADHD + Full IQ score < 80. They were afterwards administered the CPT II (Continuous Performance Test). A total of 215 children were included in the study, 57% of them with ADHD IQ > 80 and 43% with ADHD + Lower Intellectual Performance (LIP). Patients with ADHD and Lower Intellectual Performance presented more omissions error, slower reaction time and greater variability in the performance as the tests progresses, as well as worse stimulus detection and discrimination capacity. The results observed supply new information for the proper understanding of the functioning of attention processes in a poorly studied population.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Atenção/fisiologia , Deficiência Intelectual/diagnóstico , Testes Neuropsicológicos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Estudos Transversais , Feminino , Humanos , Deficiência Intelectual/psicologia , Masculino , Tempo de Reação/fisiologiaRESUMO
The objective of this study was to characterize an attention deficit hyperactivity disorder (ADHD) endophenotype in non-affected parents of adolescents with a history of ADHD, based on the relationship between performance on a sustained attention test (continuous performance task, or CPT) and polymorphisms of the DRD4 gene. In a sample of 25 non-affected parents of adolescents with ADHD history obtained from a longitudinal study of a nonclinical population, and 25 non-affected parents of adolescents with no ADHD history, four groups were evaluated with respect to the presence or absence of the long allele polymorphism of the DRD4 gene (i.e., over seven repeats). Comparisons of CPT performance among the four study groups included the number of commission errors, the number of omission errors, mean reaction time on correct responses (MRT), and reaction time (RT) variability (mean standard deviation of RT in each block [SDRT, as variability], and the sigma and tau components of the ex-Gaussian approach). The group of non-affected parents of adolescents with ADHD history and at least one long allele of the DRD4 gene showed greater RT variability (measured by SDRT), which is best explained by the greater frequency of abnormally slow responses (measured by tau). An association between the presence of the long allele of the DRD4 gene polymorphism and ADHD-like failure in CPT performance was evident in the non-affected parents of adolescents with ADHD in childhood. These findings suggest that certain traits of CPT performance could be considered an ADHD endophenotype.
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Transtorno do Deficit de Atenção com Hiperatividade/genética , Receptores de Dopamina D4/genética , Adulto , Alelos , Atenção/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Cognição/fisiologia , Endofenótipos , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Pais , Polimorfismo de Nucleotídeo Único/genética , Tempo de Reação/genética , Receptores de Dopamina D4/sangueRESUMO
This study investigates the effects of replacing dietary casein by soya protein on the underlying mechanisms involved in the impaired metabolic fate of glucose and lipid metabolisms in the heart of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). To test this hypothesis, Wistar rats were fed an SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed an SRD in which casein was substituted by soya. The control group received a diet with maize starch as the carbohydrate source. Compared with the SRD-fed group, the following results were obtained. First, soya protein significantly (P<0·001) reduced the plasma NEFA levels and normalised dyslipidaemia and glucose homoeostasis, improving insulin resistance. The protein levels of fatty acid translocase at basal state and under insulin stimulation and the protein levels and activity of muscle-type carnitine palmitoyltransferase 1 were normalised. Second, a significant (P<0·001) reduction of TAG, long-chain acyl CoA and diacylglycerol levels was observed in the heart muscle. Third, soya protein significantly increased (P<0·01) GLUT4 protein level under insulin stimulation and normalised glucose phosphorylation and oxidation. A reduction of phosphorylated AMP protein kinase protein level was recorded without changes in uncoupling protein 2 and PPARα. Fourth, hydroxyproline concentration decreased in the left ventricle and hypertension was normalised. The new information provided shows the beneficial effects of soya protein upon the altered pathways of glucose and lipid metabolism in the heart muscle of this rat model.
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Dislipidemias/metabolismo , Glucose/metabolismo , Hipertensão/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Miocárdio/metabolismo , Proteínas de Soja/administração & dosagem , Animais , Carnitina O-Palmitoiltransferase/análise , Proteínas Alimentares/administração & dosagem , Sacarose Alimentar/administração & dosagem , Modelos Animais de Doenças , Ácidos Graxos não Esterificados/sangue , Glucose/administração & dosagem , Hidroxiprolina/análise , Insulina/sangue , Resistência à Insulina/fisiologia , Masculino , Miocárdio/enzimologia , PPAR alfa/análise , Ratos , Ratos WistarRESUMO
Conjugated linoleic acid (CLA) might regulate the lipid depots in liver and adipose tissue. As there is an association between maternal nutrition, fat depots and risk of offspring chronic disease, the aim was to investigate the effect of maternal CLA consumption on TAG regulation and some inflammatory parameters in adult male rat offspring receiving or not receiving CLA. Female Wistar rats were fed control (C) or CLA-supplemented (1 %, w/w) diets during 4 weeks before and throughout pregnancy and lactation. After weaning, male offspring of CLA rats were fed C or CLA diets (CLA/C and CLA/CLA groups, respectively), whereas C male rat offspring were fed a C diet (C/C group) for 9 weeks. Serum TAG levels were increased in the CLA/CLA and CLA/C groups, associated with a reduction of lipoprotein lipase activity and weights of adipose tissue. The liver TAG levels were decreased in the CLA/CLA group, related to a significant reduction of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and glucose-6-phosphate dehydrogenase enzyme activities, as well as to the mRNA levels of FAS, ACC, stearoyl-CoA desaturase-1 and sterol regulatory element-binding protein-1c. Even though normal TAG levels were found in the liver of CLA/C rats, a reduction of lipogenesis was also observed. Thus, these results demonstrated a programming effect of CLA on the lipid metabolic pathways leading to a preventive effect on the TAG accretion in adipose tissue and the liver of male rat offspring. This knowledge could be important to develop some dietary strategies leading to a reduced incidence of obesity and fatty acid liver disease in humans.
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Fenômenos Fisiológicos da Nutrição Animal , Ácidos Linoleicos Conjugados/farmacologia , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Dieta , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/sangue , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/sangue , Feminino , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
OBJECTIVES: We aimed to determine whether carvacryl acetate acts as a TRPA1 receptor agonist and its effects against irinotecan (CPT-11) induced intestinal mucositis in mice. METHODS: TRPA1 structure was obtained from a protein databank, and the 3D structure of carvacryl acetate was determined. Appropriate binding conformations were discovered via automatic docking simulations. To determine the effect of carvacryl acetate in vivo, mice were treated with either DMSO 2%, CPT-11, carvacryl acetate followed by CPT-11, or HC-030031, a TRPA1 antagonist, followed by carvacryl acetate. Jejunum samples were taken and structural, inflammatory and antioxidant parameters were studied. KEY FINDINGS: Eight amino acids residues in TRPA1 established stable interactions with carvacryl acetate, which led to pharmacological efficacy against CPT-11-induced intestinal mucositis via reduction of both neutropenia and bacteremia, increase in villi height and crypt depth, decrease in pro-inflammatory cytokines (interleukin-1ß, keratinocyte chemoattractant and tumour necrosis factor-α) and decrease in malondialdehyde and nitric oxide metabolite levels in the jejunum. CONCLUSIONS: Carvacryl acetate is a promising anti-inflammatory and antioxidant agent, a fact confirmed through observations of its interactions with TRPA1 in CPT-11-induced intestinal mucositis in mice.
Assuntos
Anti-Inflamatórios/farmacologia , Camptotecina/análogos & derivados , Monoterpenos/farmacologia , Mucosite/prevenção & controle , Animais , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/farmacologia , Bacteriemia/prevenção & controle , Camptotecina/toxicidade , Citocinas/metabolismo , Feminino , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Irinotecano , Jejuno/metabolismo , Jejuno/patologia , Camundongos , Simulação de Acoplamento Molecular , Mucosite/induzido quimicamente , Neutropenia/prevenção & controle , Canal de Cátion TRPA1/agonistasRESUMO
Paracrine regulation of Sertoli cell function by germ cells is an outstanding characteristic of testicular physiology. It has been demonstrated that Sertoli cells produce ketone bodies and that germ cells may use them as energy source. The aim of the study was to analyze a possible regulation by germ cells of ketogenesis in Sertoli cells. Cultures of Sertoli cells (SC) obtained from 31-day-old rats were co-cultured with germ cells (GC). The results presented herein show that the presence of GC stimulated 3-hydroxybutyrate production and increased mRNA levels of two enzymes involved in ketogenesis-carnitine palmitoyltransferase 1a (CPT1a) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (mHMGCoA) synthase- in SC. Additionally, GC increased monocarboxylate transporter 4 (Mct4) expression in SC, a transporter involved in ketone bodies exit. To evaluate if the observed effects might be mediated by soluble factors, SC cultures were incubated with germinal cell-conditioned medium (GCCM) or with two growth factors, bFGF and IGF1, which are known to be secreted by GC. We observed that GCCM and bFGF stimulated ketone bodies production but that IGF1 did not modify it. Also, we observed that GCCM and bFGF increased Cpt1a and Mct4 mRNA levels. In summary, results presented herein demonstrate that Sertoli cells are able to produce ketone bodies and that its production is regulated in a paracrine way by germ cells. This study adds new information about communication between Sertoli cells and developing germ cells.
Assuntos
Ácido 3-Hidroxibutírico/biossíntese , Células Germinativas/metabolismo , Células de Sertoli/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Germinativas/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Corpos Cetônicos/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Células de Sertoli/efeitos dos fármacosRESUMO
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a developmental disorder. Continuous performance Tests (CPTs) aid the diagnosis. Handedness is linked to disabilities. OBJECTIVES: 1-To study the association between handedness and ADHD; 2-To verify the usefulness of the CPT in school settings; 3-To exam the relationship between handedness and CPT performance. METHOD: Each child was classified as right-consistent, left-consistent, or non-consistent. From the sample, 171 controls and 68 ADHDs fulfilled the inclusion criteria. The effect of handedness on the CPT was studied using a paired-sample that matched handedness by age, grade, gender, and ADHD. RESULTS: Left-handed students had a probability of suffering from ADHD 2.88 greater than right-handers. ANOVAs on standardized scores indicated that the ADHD students exhibited higher number of errors and higher variability of reaction times as compared to the controls. Discriminant analysis indicated that these CPT parameters could discriminate ADHD from controls. Repeated ANOVAs showed a significant effect of handedness on commission errors (CE) because left-handers made more CEs than right-handers. CONCLUSIONS: 1-The association between ADHD and handedness reflects that left-handers are less lateralized and have decreased interhemispheric connections; 2-The CPT can be used to measure different attention domains in school settings; 3- Left-handers have problems in the impulsive/hyperactivity domain.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Atenção/fisiologia , Lateralidade Funcional , Comportamento Impulsivo/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação/fisiologia , Estatística como Assunto , Análise e Desempenho de TarefasRESUMO
C75 is a synthetic anticancer drug that inhibits fatty acid synthase (FAS) and shows a potent anorexigenic side effect. In order to find new cytotoxic compounds that do not impact food intake, we synthesized a new family of C75 derivatives. The most promising anticancer compound among them was UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one). The effects of this compound on cytotoxicity, food intake and body weight were studied in UB006 racemic mixture and in both its enantiomers separately. The results showed that both enantiomers inhibit FAS activity and have potent cytotoxic effects in several tumour cell lines, such as the ovarian cell cancer line OVCAR-3. The (-)-UB006 enantiomer's cytotoxic effect on OVCAR-3 was 40-fold higher than that of racemic C75, and 2- and 38-fold higher than that of the racemic mixture and its opposite enantiomer, respectively. This cytotoxic effect on the OVCAR-3 cell line involves mechanisms that reduce mitochondrial respiratory capacity and ATP production, DDIT4/REDD1 upregulation, mTOR activity inhibition, and caspase-3 activation, resulting in apoptosis. In addition, central and peripheral administration of (+)-UB006 or (-)-UB006 into rats and mice did not affect food intake or body weight. Altogether, our data support the discovery of a new potential anticancer compound (-)-UB006 that has no anorexigenic side effects.
Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintases/antagonistas & inibidores , Furanos/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ingestão de Alimentos/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Ácido Graxo Sintases/metabolismo , Furanos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-DawleyRESUMO
Background: Several investigations report to rosemary as a plant rich in bioactive components with antioxidant potential, in this work, a rosemary extract was obtained that combined with ascorbyl palmitate provides a synergistic protection to a high fat diet (palm olein). Objectives: The objective of this study was to evaluate the effect of the addition of two extracts of rosemary (Rosmarinus officinalis): AP10R and AP30R at three concentrations of 1000, 1500 and 2000 ppm, on the oxidative stability of palm oil subjected to accelerated oxidation conditions and in a frying process. Methods: Lipid peroxidation of palm olein with and without antioxidants was monitored by measuring the concentration of hydroperoxides and total polar compounds; the thermal stability of the phenolic compounds in the oil was evaluated by fluorescence spectroscopy. Results: The AP10R extract at 2000 ppm inhibited olein oxidation by 30% and 60% in terms of total hydroperoxide and polar concentrations, respectively. The AP30 extract at 2000 ppm had similar inhibition behaviors with values of 27% of total hydroperoxides and 54% by total polar compounds in a time from 20 to 25 h. Conclusions: The results indicated that heating reduces the concentration of polyphenols; this decrease was more evident in olein without antioxidants, reflecting the effect of the polyphenols of rosemary extract on the thermal stability of palm olein.
Antecedentes: Diversas investigaciones reportan al romero como una planta rica en componentes bioactivos con potencial antioxidante, en este trabajo, se obtuvo un extracto de romero que combinado con ascorbil palmitato brinda una protección sinérgica a un sistema alimenticio con alto contenido graso (oleína de palma). Objetivos: El objetivo de este estudio fue evaluar el efecto de la adición de dos extractos de romero (Rosmarinus officinalis): AP10R y AP30R a tres concentraciones de 1000, 1500 y 2000 ppm, sobre la estabilidad oxidativa del aceite de palma sometido a condiciones de oxidación acelerada y en un proceso de fritura. Métodos: La peroxidación lipídica de la oleína de palma con y sin antioxidantes fue monitoreada midiendo la concentración de hidroperóxidos y los compuestos polares totales; la estabilidad térmica de los compuestos fenólicos en el aceite se evaluó por espectroscopia de fluorescencia. Resultados: El extracto AP10R a 2000 ppm inhibió la oxidación de oleína en 30% y 60% en términos de la concentración de hidroperóxidos y polares totales, respectivamente. El extracto AP30 a 2000 ppm tuvo comportamientos similares de inhibición con valores de 27% para hidroperóxidos y 54% para el contenido de fenoles totales en un tiempo de 20 a 25 h. Conclusiones: Los resultados indicaron que el calentamiento disminuye la concentración de polifenoles; esta disminución fue más evidente en la oleína sin antioxidantes, reflejando el efecto de los polifenoles del extracto de romero sobre la estabilidad térmica de la oleína de palma.