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1.
Psychol Med ; 47(2): 255-266, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27697085

RESUMO

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70). METHOD: The participants (n = 1857, aged 6-15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates. RESULTS: In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children. CONCLUSION: The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Discriminação Psicológica/fisiologia , Dislexia/fisiopatologia , Reconhecimento Visual de Modelos/fisiologia , Leitura , Adolescente , Criança , Feminino , Humanos , Masculino
2.
Psychol Med ; 47(4): 744-754, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27866484

RESUMO

BACKGROUND: There are still uncertainties on the psychometric validity of the DSM-5 attention deficit hyperactivity disorder (ADHD) criteria for its use in the adult population. We aim to describe the adult ADHD phenotype, to test the psychometric properties of the DSM-5 ADHD criteria, and to calculate the resulting prevalence in a population-based sample in their thirties. METHOD: A cross-sectional evaluation using the DSM-5 ADHD criteria was carried out in 3574 individuals from the 1982 Pelotas Birth Cohort. Through receiver operator curve, latent and regression analyses, we obtained parameters on construct and discriminant validity. Still, prevalence rates were calculated for different sets of criteria. RESULTS: The latent analysis suggested that the adult ADHD phenotype is constituted mainly by inattentive symptoms. Also, inattention symptoms were the symptoms most associated with impairment. The best cut-off for diagnosis was four symptoms, but sensitivity and specificity for this cut-off was low. ADHD prevalence rates were 2.1% for DSM-5 ADHD criteria and 5.8% for ADHD disregarding age-of-onset criterion. CONCLUSIONS: The bi-dimensional ADHD structure proposed by the DSM demonstrated both construct and discriminant validity problems when used in the adult population, since inattention is a much more relevant feature in the adult phenotype. The use of the DSM-5 criteria results in a higher prevalence of ADHD when compared to those obtained by DSM-IV, and prevalence would increase almost threefold when considering current ADHD syndrome. These findings suggest a need for further refinement of the criteria for its use in the adult population.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Escalas de Graduação Psiquiátrica/normas , Psicometria/instrumentação , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Brasil/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
3.
Psychol Med ; 45(2): 361-73, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25066615

RESUMO

BACKGROUND: The DSM criteria for adult attention-deficit/hyperactivity disorder (ADHD) have not been tested in American Psychiatric Association (APA) field trials for either DSM-IV or DSM-5. This study aimed to assess: (a) the prevalence of ADHD according to DSM-5 criteria; (b) the factor solution that provides the best fit for ADHD symptoms; (c) the symptoms with the highest predictive value for clinical impairment; and (d) the best symptomatic threshold for each ADHD dimension (inattention and hyperactivity/impulsivity). METHOD: Trained psychologists evaluated 4000 young adults from the 1993 Pelotas Birth Cohort Study with an instrument covering all DSM-5 ADHD criteria. A series of confirmatory factor analyses (CFAs) tested the best factor structure. Complex logistic regressions assessed differential contributions of each symptom to clinical impairment. Receiver-operating characteristic (ROC) analyses tested which would be the best symptomatic cut-off in the number of symptoms for predicting impairment. RESULTS: The prevalence of DSM-5 ADHD was 3.55% [95% confidence interval (CI) 2.98-4.12]. The estimated prevalence of DSM-IV ADHD was 2.8%. CFA revealed that a bifactor model with a single general factor and two specific factors provided the best fit for DSM-5 symptoms. Inattentive symptoms continued to be the most important predictors of impairment in adults. The best cut-offs were five symptoms of inattention and four symptoms of hyperactivity/impulsivity. CONCLUSIONS: Our results, combined with previous findings, suggest a 27% increase in the expected prevalence of ADHD among young adults, comparing DSM-IV to DSM-5 criteria. The DSM-5 symptomatic organization derived a similar factor structure for adults as DSM-IV symptoms. Data using DSM-5 criteria support lowering the symptomatic threshold for diagnosing ADHD in adults.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Adolescente , Estudos de Coortes , Comorbidade , Análise Fatorial , Feminino , Humanos , Modelos Logísticos , Masculino , Curva ROC , Índice de Gravidade de Doença , Adulto Jovem
4.
Psychol Med ; 45(12): 2633-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26234806

RESUMO

BACKGROUND: Research with adults suggests that anxiety is associated with poor control of executive attention. However, in children, it is unclear (a) whether anxiety disorders and non-clinical anxiety are associated with deficits in executive attention, (b) whether such deficits are specific to anxiety versus other psychiatric disorders, and (c) whether there is heterogeneity among anxiety disorders (in particular, specific phobia versus other anxiety disorders). METHOD: We examined executive attention in 860 children classified into three groups: anxiety disorders (n = 67), attention-deficit/hyperactivity disorder (ADHD; n = 67) and no psychiatric disorder (n = 726). Anxiety disorders were subdivided into: anxiety disorders excluding specific phobia (n = 43) and specific phobia (n = 21). The Attention Network Task was used to assess executive attention, alerting and orienting. RESULTS: Findings indicated heterogeneity among anxiety disorders, as children with anxiety disorders (excluding specific phobia) showed impaired executive attention, compared with disorder-free children, whereas children with specific phobia showed no executive attention deficit. Among disorder-free children, executive attention was less efficient in those with high, relative to low, levels of anxiety. There were no anxiety-related deficits in orienting or alerting. Children with ADHD not only had poorer executive attention than disorder-free children, but also higher orienting scores, less accurate responses and more variable response times. CONCLUSIONS: Impaired executive attention in children (reflected by difficulty inhibiting processing of task-irrelevant information) was not fully explained by general psychopathology, but instead showed specific associations with anxiety disorders (other than specific phobia) and ADHD, as well as with high levels of anxiety symptoms in disorder-free children.


Assuntos
Transtornos de Ansiedade/psicologia , Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção , Comportamento Infantil/fisiologia , Função Executiva , Análise de Variância , Transtornos de Ansiedade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Brasil , Criança , Comportamento Infantil/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Psicologia da Criança
5.
Psychol Med ; 44(15): 3189-201, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25065454

RESUMO

BACKGROUND: Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation. METHOD: A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data. RESULTS: Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD. CONCLUSIONS: Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/classificação , Cognição/fisiologia , Função Executiva/fisiologia , Inibição Psicológica , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Brasil/epidemiologia , Criança , Feminino , Humanos , Masculino , Índice de Gravidade de Doença
6.
Psychol Med ; 44(3): 617-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23561016

RESUMO

BACKGROUND: Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits. METHOD: We assessed 704 subjects (age 6-12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed-accuracy trade-off and encoding/motor function along with variability parameters. RESULTS: Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP. CONCLUSIONS: Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.


Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Função Executiva/fisiologia , Inibição Psicológica , Processos Mentais/fisiologia , Modelos Estatísticos , Análise de Variância , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Estudos de Casos e Controles , Criança , Comorbidade , Diagnóstico Diferencial , Medo/psicologia , Feminino , Humanos , Entrevista Psicológica , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Tempo de Reação/fisiologia , Estresse Psicológico/psicologia
7.
Psychol Med ; 43(4): 733-45, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22850475

RESUMO

BACKGROUND: Preliminary research implicates threat-related attention biases in paediatric anxiety disorders. However, major questions exist concerning diagnostic specificity, effects of symptom-severity levels, and threat-stimulus exposure durations in attention paradigms. This study examines these issues in a large, community school-based sample. Method A total of 2046 children (ages 6-12 years) were assessed using the Development and Well Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified based on presence or absence of 'fear-related' disorders, 'distress-related' disorders, and behavioural disorders. Two dot-probe tasks, which differed in stimulus exposure, assessed attention biases for happy-face and threat-face cues. The main analysis included 1774 children. RESULTS: For attention bias scores, a three-way interaction emerged among face-cue emotional valence, diagnostic group, and internalizing symptom severity (F = 2.87, p < 0.05). This interaction reflected different associations between internalizing symptom severity and threat-related attention bias across diagnostic groups. In children with no diagnosis (n = 1411, mean difference = 11.03, s.e. = 3.47, df = 1, p < 0.001) and those with distress-related disorders (n = 66, mean difference = 10.63, s.e. = 5.24, df = 1, p < 0.05), high internalizing symptoms predicted vigilance towards threat. However, in children with fear-related disorders (n = 86, mean difference = -11.90, s.e. = 5.94, df = 1, p < 0.05), high internalizing symptoms predicted an opposite tendency, manifesting as greater bias away from threat. These associations did not emerge in the behaviour-disorder group (n = 211). CONCLUSIONS: The association between internalizing symptoms and biased orienting varies with the nature of developmental psychopathology. Both the form and severity of psychopathology moderates threat-related attention biases in children.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Atenção/fisiologia , Transtornos do Comportamento Infantil/fisiopatologia , Medo/fisiologia , Adulto , Análise de Variância , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Criança , Comportamento Infantil/psicologia , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/psicologia , Estudos de Coortes , Expressão Facial , Feminino , Humanos , Modelos Lineares , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Tempo de Reação/fisiologia , Índice de Gravidade de Doença
9.
Neurosci Biobehav Rev ; 108: 295-307, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778679

RESUMO

Across numerous studies, individuals with substance use disorders (SUDs) differed from non-using controls regarding valuation of delayed gratification and feedback processing. However, it remains unclear whether the magnitude of the effect sizes is different across these two cognitive processes and how specific SUDs as well as demographic and clinical moderators influence these effects. In this study we thus performed multilevel linear mixed-effects meta-analyses and meta-regressions to examine the effects of SUDs on the Delay Discounting Task (DD) and on the Iowa Gambling Task (IGT). We found a moderate to large effect for SUD on both, the IGT and DD. While the effect on the DD was generalized to all substance classes, a smaller effect for cannabis-related disorder when compared to other SUDs was found with regard to the IGT. Early onset of substance use and psychiatric comorbidities were associated with stronger effects on the DD. Our findings suggest that feedback processing is more vulnerable to specific substance effects, while valuation of delayed gratification depends more on developmental and clinical factors.


Assuntos
Desvalorização pelo Atraso/fisiologia , Retroalimentação Psicológica/fisiologia , Recompensa , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Humanos
10.
Int J Oncol ; 28(4): 995-1002, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16525651

RESUMO

p53 wild-type is a tumor suppressor gene involved in DNA gene transcription or DNA repair mechanisms. When damage to DNA is unrepairable, p53 induces programmed cell death (apoptosis). The mutant p53 gene is the most frequent molecular alteration in human cancer, including breast cancer. Here, we analyzed the genetic alterations in p53 oncogene expression in 55 patients with breast cancer at different stages and in 8 normal women. We measured by ELISA assay the serum levels of p53 mutant protein and p53 antibodies. Immunohistochemistry and RT-PCR using specific p53 primers as well as mutation detection by DNA sequencing were also evaluated in breast tumor tissue. Serological p53 antibody analysis detected 0/8 (0%), 0/4 (0%) and 9/55 (16.36%) positive cases in normal women, in patients with benign breast disease and in breast carcinoma, respectively. We found positive p53 mutant in the sera of 0/8 (0.0%) normal women, 0/4 (0%) with benign breast disease and 29/55 (52.72%) with breast carcinoma. Immunohistochemistry evaluation was positive in 29/55 (52.73%) with mammary carcinoma and 0/4 (0%) with benign breast disease. A very good correlation between p53 mutant protein detected in serum and p53 accumulation by immunohistochemistry (83.3% positive in both assays) was found in this study. These data suggest that detection of mutated p53 could be a useful serological marker for diagnostic purposes.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Mutação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Carcinoma in Situ/sangue , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteína Supressora de Tumor p53/sangue , Proteína Supressora de Tumor p53/imunologia
11.
Transl Psychiatry ; 6: e755, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26978737

RESUMO

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.


Assuntos
Encéfalo/fisiopatologia , Dieta , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Ômega-3 , Comportamento Alimentar , Retardo do Crescimento Fetal/fisiopatologia , Comportamento Impulsivo , Adolescente , Encéfalo/diagnóstico por imagem , Sinais (Psicologia) , Tomada de Decisões , Gorduras na Dieta , Feminino , Retardo do Crescimento Fetal/metabolismo , Neuroimagem Funcional , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Fenótipo
12.
Int J Dev Neurosci ; 47(Pt B): 304-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26521949

RESUMO

An adverse early life environment can induce changes on behavioral and metabolic responses later in life. Recent studies in rats showed that the quality of maternal care as measured by high levels of pup licking and grooming (LG) was associated with changes in the relationship between the precursor thyroid-hormone T4 and the more active T3. Here we investigated if early exposure to childhood abuse is associated with thyroid-hormone levels in human adolescents. Given the empirical evidence from animal models showing that good maternal care was associated with increased conversion of T4 to T3, we hypothesized that early adversity would be associated with a decreased peripheral conversion of T4 to T3. A sample of 80 adolescents (10-18 years) participated in this study. We used the Childhood Trauma Questionnaire to investigate early life stress. We calculate the body mass index (BMI) assessing weight and height and sexual maturation stage was determined by self-assessment. Blood samples were collected to measure T3 and T4 levels. ANCOVA were used to evaluate the influence of the Physical Abuse domain of the Childhood Trauma Questionnaire as the early life stress variable in T3 and T4 separately, adjusted for potential confounders such as pubertal status, gender, socioeconomic status and BMI. Early life trauma was associated with reduced T3 levels in adolescents, when adjusted for potential confounders (p=0.013), but not with peripheral T4 levels (p=0.625). We extended findings from animal models showing that adverse early experience persistently impacts on the individual's responses to stress, which is marked by an abnormal metabolism of thyroid hormones. Further studies are needed to further investigate the nature of such associations.


Assuntos
Tri-Iodotironina/sangue , Ferimentos e Lesões/sangue , Adolescente , Análise de Variância , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , Abuso Físico , Inquéritos e Questionários , Tiroxina/sangue
13.
Transl Psychiatry ; 2: e195, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23168995

RESUMO

Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena.


Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo/sangue , Comportamento Materno/psicologia , Estresse Psicológico/sangue , Adolescente , Animais , Ansiedade/sangue , Ansiedade/genética , Ansiedade/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Criança , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Ratos , Estresse Psicológico/genética
14.
Arq. bras. med. vet. zootec ; 63(1): 203-213, Feb. 2011. tab
Artigo em Português | LILACS | ID: lil-582345

RESUMO

Avaliou-se o efeito da ractopamina e de diferentes métodos de formulação de dietas sobre o desempenho e as características de carcaça de leitoas em terminação. Foram utilizadas 60 leitoas, híbridas comerciais, distribuídas em delineamento experimental de blocos ao acaso, em esquema fatorial 2x3, sendo dois níveis de ractopamina e três métodos de formulação de dietas. Houve interação de métodos de formulação versus ractopamina para ganho de peso diário, peso corporal, conversão alimentar e taxa de deposição de carne magra (TDCM) na avaliação de carcaça in vivo por ultrassom. A dieta formulada com alta proteína bruta proporcionou maior consumo de dieta (CRD), de lisina (CLD), ganho de peso diário (GPD) e peso corporal final. A suplementação de ractopamina não influenciou o CRD e o CLD, entretanto aumentou o GPD. O método de formulação da dieta não influenciou as características de carcaça aos 28 dias, enquanto a suplementação de ractopamina reduziu a espessura de toucinho, aumentou a profundidade de lombo e o rendimento de carne magra. A dieta formulada com alta proteína bruta proporcionou melhores resultados de desempenho e taxa de deposição de carne magra na carcaça de leitoas em terminação, suplementadas com ractopamina.


The effect of ractopamine supplementation and feed formulation methods was evaluated on performance and carcass characteristics of finishing gilts. Sixty animals were allotted in a completely randomized block experimental design, in a 2x3 factorial scheme - ractopamine (0 and 5ppm) X three feed formulation methods. Interactions between feed formulation method and ractopamine for daily weight gain (DWG), body weight, feed:gain (DFG), and lean carcass meat deposition (LCMD) were by in vivo carcass evaluation using ultrasound observed. Daily feed intake (DFI), lysine intake (DLI), DWG, and final body weight were higher for diets with high protein level. Ractopamine supplementation did not affect feed intake, and lysine intake, but increased daily weight gain. Feed formulation method affected carcass characteristics recorded at 28 days, while ractopamine supplementation reduced backfat thickness, increased muscle depth, and lean carcass proportion of the gilts. Ractopamine improved performance and carcass characteristics of finishing gilts and feed formulation methods affected performance and carcass characteristics. Better performance and higher lean carcass deposition were observed for finishing gilts fed high protein level diets supplemented with ractopamine.


Assuntos
Animais , Ração Animal/análise , Suínos/classificação , Dieta , Lisina/análise
15.
Ann Oncol ; 11(2): 177-81, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10761752

RESUMO

BACKGROUND: Although not clearly defined, 'hormone refractory' prostate cancer implies disease progression after orchiectomy +/- antiandrogens. Patients in this setting are usually offered chemotherapy protocols which often lead to significant toxicity and expense. In search of a well-tolerated, active, third-line treatment, we have attempted to prolong hormonal maneuvers by using low-dose estrogen therapy. DESIGN: Thirty-eight patients with evidence of disease progression (as indicated by 2 consecutively rising PSA determinations) after > or = 2 hormonal treatments (including surgical or chemical orchiectomy and a median of 3 prior treatment lines) received fosfestrol 100 mg t.i.d. per os in a continuous schedule until the appearance of progressive disease or excessive toxicity. Response was assessed by serial PSA levels. Complete response (CR) was defined as normalisation and partial response (PR) as a > or = 50 decrease of PSA levels for longer than one month. The median duration of prior treatment was 20 months and the median PSA at fosfestrol start was 126 ng/ml (range 8-12,800); symptoms (pain) were present in 73% of patients. RESULTS: CR + PR were observed in 79% (95% confidence interval: 66%-92%). The median time to progression was seven months. Pain remained stable or improved in 34% and 53%, respectively, of symptomatic patients with PSA response. Toxicity included worsening of gynecomastia, peripheral edema, and deep vein thrombosis (8%). No treatment-related deaths occurred. Uni- and multivariate analyses failed to identify predictive factors for response. PSA response was associated with significantly longer survival (13 vs. 7 months, P < 0.05 by Mantel-Haentzel). CONCLUSIONS: FOSF produces high rates of PSA-determined and symptomatic response in 'hormone-refractory' prostate cancer. Toxicity and ease of administration compare favorably with those reported for CHT regimens used in this setting. The role of estrogens in prostate cancer should be redefined.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Dietilestilbestrol/análogos & derivados , Antígeno Prostático Específico/análise , Neoplasias da Próstata/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Dietilestilbestrol/administração & dosagem , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
16.
Am J Clin Oncol ; 27(2): 149-54, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15057154

RESUMO

The purpose of this report is to evaluate the efficacy and toxicity (Tx) of a double modulation of 5-fluorouracil (5-FU) by trimetrexate (TMTX) and leucovorin (LV) in patients with advanced recurrent (inoperable) or metastatic colorectal cancer (ACC). Between December 1997 and August 2000, 36 patients were entered in this phase II study. Median age was 61 years, and 18 patients (50%) were female. Median performance status was 0 (range: 0-1), whereas primary tumor location was colon in 21 patients (58%) and rectum in 15 patients (42%). The number of metastatic sites was 1:29 patients (81%); 2:6 patients (17%) and 3:1 patient (3%). Hepatic involvement was observed in 33 patients (92%). Treatment consisted of TMTX 110 mg/m2 IV over 1 hour at hour (H) 0; LV 50 mg/m2 IV over 2 hours IV infusion starting at H 18; and 5-FU 900 mg/m2 IV bolus at H 20. LV (rescue) 15 mg/m2 orally was administered every 6 hours (total 6 doses) beginning at H 24. Cycles were repeated every 2 weeks until progressive disease (PD) or severe Tx. Thirty-four patients are assessable for response (R) (two patients refused further treatment after the first course of therapy), whereas all patients were assessable for Tx. Complete response: 1 patient (3%); partial response: 4 patients (12%), with an overall objective response rate of 15% (95% CI, 1%-25%); no change: 12 patients (35%); and progressive disease: 17 patients (50%). The median time to treatment failure was 4 months and median survival was 11 months. Tx was within acceptable limits. The dose-limiting side effect was mucositis. Eight episodes of grade II or III stomatitis were observed and were responsible for dosage modifications of TMTX and 5-FU. Leukopenia was observed in 16 patients (44%); neutropenia was registered in 19 patients (53%); anemia was seen in 18 patients (50%); emesis in 22 patients (61%); and dermatitis in 3 patients (8%). There were no therapy-related deaths. The double modulation of 5-FU by TMTX and LV showed modest antitumoral activity with mild to moderate Tx.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Análise de Sobrevida , Falha de Tratamento , Trimetrexato/administração & dosagem
17.
Arq. bras. med. vet. zootec ; 60(4): 943-952, ago. 2008. tab
Artigo em Português | LILACS | ID: lil-489840

RESUMO

Avaliaram-se os efeitos da ractopamina e de dois níveis de lisina digestível na dieta sobre o desempenho e características de carcaça de leitoas com peso corporal a partir de 85kg, durante 21 e 28 dias antes do abate, os quais foram distribuídos em delineamento experimental de blocos ao acaso com cinco repetições de dois animais por unidade experimental. Os tratamentos consistiram de arranjo fatorial 2x2, com dois níveis de lisina digestível (LD), 0,67 e 0,87 por cento, e dois níveis de ractopamina (0 e 5ppm). Observou-se efeito significativo do nível de LD sobre o ganho de peso e peso corporal e interação significativa (P<0,05) entre o nível de LD e a ractopamina sobre a conversão alimentar e sobre a taxa de deposição de carne magra corporal. Não houve efeito significativo (P>0,05) do nível de LD sobre a espessura de toucinho, profundidade de lombo e rendimento em carne magra da carcaça de acordo com avaliação da carcaça, feita in vivo. Não houve efeito (P>0,05) da ractopamina sobre o consumo de ração, o ganho de peso diário e o peso corporal aos 21 e 28 dias de experimento. A ractopamina reduziu a espessura de toucinho no ponto P2 aos 21 dias e aumentou o rendimento de carne magra e a profundidade de lombo na avaliação da carcaça no frigorífico.


The effects of ractopamine and digestible lysine levels on performance and carcass traits of gilts with initial body weight average of 85kg, recorded during 21 and 28 day before slaughtering time were evaluated in a completely randomized block design with five replicates of two animals per experiment unit. The treatments consisted in a 2 x 2 factorial scheme, two levels of digestible lysine (DL) (0.67 and 0.87 percent) and two ractopamine levels (0 and 5ppm). Significant effects of DL on daily weight gain and body weight and significant effects of DL and ractopamine level were observed for feed:weight gain ratio and lean meat carcass deposition. No significant effects (P>0.05) of DL on fat thickness, muscle depth and lean meat yield according to the in vivo carcass evaluation were observed. No significant effect of ractopamine (P>0.05) on feed intake, daily weight gain and body weight (21 and 28 days) were observed. Ractopamine reduced back fat thickness at P2 point (21days) and increased lean meat yield and muscle depth in frigorific carcass evaluation.


Assuntos
Animais , Feminino , Dieta , Lisina/efeitos adversos , Suínos
18.
Arq. bras. med. vet. zootec ; 59(5): 1270-1277, out. 2007. ilus, tab
Artigo em Português | LILACS | ID: lil-471212

RESUMO

Avaliaram-se o desempenho e as características morfológicas e morfométricas do intestino delgado de 210 leitões, desmamados aos 15 dias de idade, com peso médio inicial 4,04±0,66kg, em dois períodos experimentais (15-30 e 15-36 dias de idade). O delineamento experimental foi em blocos ao acaso, com sete tratamentos (T1: ração-controle sem adição de acidificante; T2: ração-controle + 0,5 por cento de ácido fumárico; T3: ração-controle + 1,0 por cento de ácido fumárico; T4: ração-controle + 0,5 por cento de ácido fumárico +0,1 por cento de ácido butírico; T5: ração-controle + 0,5 por cento de ácido fumárico + 0,5 por cento de ácido fórmico; T6: ração-controle + 1,0 por cento de ácido fumárico + 0,1 por cento de ácido butírico e T7: ração-controle + 1,0 por cento de ácido fumárico +0,5 por cento de ácido fórmico), cinco repetições e seis animais por unidade experimental. O peso dos leitões aos 30 dias de idade não foi influenciado pelos tratamentos, mas houve efeito significativo de tratamento sobre ganho de peso e consumo alimentar diário no período de 15-30 dias de idade, com maior desempenho para os leitões alimentados com dietas suplementadas com ácido fumárico. Não houve efeito significativo dos tratamentos sobre o peso médio aos 36 dias, o ganho de peso, o consumo diário e a conversão alimentar dos leitões de 15 a 36 dias de idade. Houve diferença entre tratamentos para a altura do epitélio do duodeno, porém não houve diferença em relação à do jejuno e à do íleo. As eletromicrografias do duodeno dos leitões alimentados com as diferentes dietas experimentais revelaram vilosidades com características normais


Performance, morphological and morphometric characteristics of the small intestine of 210 recently weaned piglets, averaging 4.04 ± 0.66 kg, during two periods ( from 15 to 30 days of age and from 15 to 36 days of age) were evaluated in a randomized block experimental design with seven treatments, T1: control diet (CD); T2: CD + 0.5 percent fumaric acid; T3: CD + 1.0 percent fumaric acid; T4: CD + 0.5 percent fumaric acid + 0.1 percent butyric acid; T5: CD + 0.5 percent fumaric acid + 0.5 percent formic acid; T6: CD + 1,0 percent fumaric acid + 0.1 percent butyric acid and T7: CD + 1.0 percent fumaric acid + 0.5 percent formic acid, five replicates and six piglets per experimental unit. No effects of treatment (P<0.05) on body weight at 30 days of age was observed but significant differences between treatments were observed for daily weight gain and feed consumption from 15 to 30 days of age. Piglets fed supplemented acid fumaric diets had higher performance during this period. No significant effects of treatments on body weight at 36 days of age, daily weight gain, daily feed intake and feed conversion were observed (P>0.05) from 16 to 36 days of age. Significant differences (P<0.05) between treatments for duodenal epithelium height were observed, but not for jejunum and ileum epithelium heights. Normal villus patterns were observed in the electromicrographs of duodenum from piglets fed all different diets


Assuntos
Animais , Ácido Butírico/administração & dosagem , Dieta/veterinária , Formicicum Acidum/administração & dosagem , Fumaricum Acidum/administração & dosagem , Aumento de Peso/fisiologia , Intestino Delgado/anatomia & histologia , Intestino Delgado , Suínos/crescimento & desenvolvimento , Desmame
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