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1.
J Intellect Disabil Res ; 68(5): 464-476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38258970

RESUMO

BACKGROUND: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS. METHODS: Participants were 41 males (M age = 18 years) with FXS and co-occurring autism. Interaction samples were coded for expression of predominately 'active' (characterised by a desire to make social approaches) or 'passive' (characterised by lack of initiation of social approach towards others) interaction profiles. Differences in the expression of phenotypic features of FXS, including anxiety, attention-deficit/hyperactivity disorder, cognitive, adaptive and language impairments and autism symptom severity, were examined across those with passive and active interaction styles. RESULTS: Approximately half of the sample was classified as active and half as passive, demonstrating diversity in the social phenotype of autism associated with FXS. The two subtypes did not differ in autism severity, anxiety or attention-deficit/hyperactivity disorder symptoms or in cognitive, adaptive or language abilities. CONCLUSIONS: This study enhances understanding of FXS-associated autism by documenting phenotypic variability in the social interaction profile in this group, with active and passive social interaction styles represented. The two social interaction styles were not associated with differential expression of common phenotypic features of FXS, suggesting similar support needs.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Síndrome do Cromossomo X Frágil , Transtornos da Linguagem , Masculino , Humanos , Adulto Jovem , Adolescente , Síndrome do Cromossomo X Frágil/complicações , Interação Social , Ansiedade , Transtorno do Espectro Autista/complicações
2.
J Intellect Disabil Res ; 64(4): 296-302, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020687

RESUMO

BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder highly associated with anxiety; however, measuring anxiety symptoms in FXS and other neurogenetic syndromes is challenged by common limitations in language, self-awareness and cognitive skills required for many traditional assessment tasks. Prior studies have documented group-level differences in threat-related attentional biases, assessed via eye tracking, in FXS and non-FXS groups. The present study built on this work to test whether attentional biases correspond to clinical features of anxiety among adolescents and young adults with FXS. METHODS: Participants included 21 male adolescents with FXS ages 15-20 years who completed an adapted eye-tracking task that measured attentional bias towards fearful faces of varied emotional intensity. RESULTS: Among participants without anxiety disorders, attentional bias towards fear increased across age, similar to non-FXS paediatric anxiety samples. In contrast, participants with anxiety disorders exhibited greater stability in fear-related attentional biases across age. Across analyses, subtle fear stimuli were more sensitive to within-group anxiety variability than full-intensity stimuli. CONCLUSIONS: Our results provide novel evidence that although threat-related attentional biases may correspond with anxiety outcomes in FXS, these associations are complex and vary across developmental and task factors. Future studies are needed to characterise these associations in more robust longitudinal samples, informing whether and how eye-tracking tasks might be optimised to reliably predict and track anxiety in FXS.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Viés de Atenção/fisiologia , Síndrome do Cromossomo X Frágil/epidemiologia , Síndrome do Cromossomo X Frágil/psicologia , Adolescente , Adulto , Transtornos de Ansiedade/fisiopatologia , Comorbidade , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Masculino , Adulto Jovem
3.
J Intellect Disabil Res ; 62(10): 842-853, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30155926

RESUMO

BACKGROUND: Impairment in initiating joint attention (IJA) is associated with autism spectrum disorder (ASD) in children, although it is unclear when impairments arise. Due to the early development of IJA use and late diagnosis of ASD, groups at high-risk of ASD, such as infants with an older sibling with ASD (ASIBs) and infants with fragile X syndrome (FXS), provide opportunities to study early IJA behaviours for children who are later diagnosed with ASD. This study analysed these two groups to determine if IJA use differed compared with typically developing (TD) peers at 12 months and whether IJA was associated with later ASD outcomes. METHOD: An experimental attention task was used to analyse IJA gaze shifts and gestures in the high-risk groups. Clinical best estimate diagnoses were given to each participant to compare IJA behaviours to ASD severity. RESULTS: No differences in the frequency of IJA gaze shifts and gestures were found between 12-month-old ASIBs and TD controls, but infants with FXS demonstrated a significantly reduced range of IJA gaze shifts relative to TD controls. Additionally, ASD outcomes at 24 months were related to IJA use for infants with FXS at 12 months, but not infant ASIBs, although these findings were explained by differences in nonverbal cognitive development. CONCLUSIONS: Although previous studies have reported delays in IJA use in children with FXS and ASIBs at ages 21 and 14 months, respectively, our results suggest IJA behaviours for these high-risk groups are not distinct from TD children at 12 months. When differences were found at 12 months, they were explained by nonverbal cognitive development, particularly for infants with FXS. Differences in IJA use at 12 months in this study were too small to serve as a potential indicator of later ASD.


Assuntos
Atenção/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Fixação Ocular/fisiologia , Síndrome do Cromossomo X Frágil/fisiopatologia , Gestos , Comportamento do Lactente/fisiologia , Relações Interpessoais , Comportamento Social , Feminino , Humanos , Lactente , Masculino
4.
J Intellect Disabil Res ; 61(10): 916-927, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28895261

RESUMO

BACKGROUND: The FMR1 premutation, caused by a CGG trinucleotide repeat expansion on the FMR1 gene, has been identified as a genetic risk factor for mood and anxiety disorders. Building on recent studies identifying increased risk for mood and affective disorders in this population, we examined effects of potential protective factors (optimism, religion, hope) on depression and anxiety diagnoses in a prospective, longitudinal cohort. METHODS: Eighty-three women with the FMR1 premutation participated in the Structured Clinical Interview for DSM-IV-TR Disorders at two-time points, 3 years apart. Participants also completed measures of optimism, religion, personal faith, hope, and child and family characteristics. We used logistic regression to examine correlates of major depressive disorder (MDD) and anxiety disorders at the initial assessment, as well as predictors of the diagnostic course over time. RESULTS: Lower optimism and higher religious participation relevant to fragile X syndrome at the initial assessment were associated with a lifetime history of MDD. Lower optimism also predicted the occurrence and reoccurrence of an anxiety disorder 3 years later. CONCLUSIONS: In women with the FMR1 premutation, elevated optimism may reduce the occurrence or severity of MDD and anxiety disorders. These findings underscore the importance of supporting mental health across the FMR1 spectrum of involvement.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Proteína do X Frágil da Deficiência Intelectual/genética , Esperança/fisiologia , Transtornos do Humor/genética , Transtornos do Humor/psicologia , Otimismo/psicologia , Religião e Psicologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Adulto Jovem
5.
J Intellect Disabil Res ; 57(9): 803-14, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22974167

RESUMO

Fragile X syndrome (FXS) is the leading genetic cause of autism, accounting for approximately 5% of autism cases with as many as 50% of individuals with FXS meeting DSM-IV-TR criteria for autistic disorder. Both FXS and idiopathic autism (IA) are attributed to genetic causes; however, FXS is an identified single gene disorder whereas autism is a complex disorder with multiple potential causes, some of which have been identified. Studies in IA have focused on the prospective longitudinal examination of infant siblings of children with autism as a target group due to their high risk of developing the disorder. We propose that this same model be applied to the study of infants with FXS. There is a lack of research focusing on the early development of autism within FXS and debate in the literature regarding how to best conceptualise this co-morbidity or whether it should be considered a co-morbid condition at all. Studying the emergence and stability of autism in infants with FXS has multiple benefits such as clarifying the underlying mechanisms of the development of autism in FXS and solidifying similarities and differences between co-morbid FXS with autism and IA. Infant research in both IA and FXS are discussed as well as conclusions and implications for practice and future research.


Assuntos
Transtorno Autístico/diagnóstico , Transtorno Autístico/epidemiologia , Síndrome do Cromossomo X Frágil/epidemiologia , Comorbidade , Diagnóstico Precoce , Humanos , Lactente , Fatores de Risco
6.
Psychol Med ; 41(3): 575-88, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20507671

RESUMO

BACKGROUND: Although psychiatric diagnostic systems have conceptualized mania as a discrete phenomenon, appropriate latent structure investigations testing this conceptualization are lacking. In contrast to these diagnostic systems, several influential theories of mania have suggested a continuous conceptualization. The present study examined whether mania has a continuous or discrete latent structure using a comprehensive approach including taxometric, information-theoretic latent distribution modeling (ITLDM) and predictive validity methodologies in the Epidemiologic Catchment Area (ECA) study. METHOD: Eight dichotomous manic symptom items were submitted to a variety of latent structural analyses, including factor analyses, taxometric procedures and ITLDM, in 10105 ECA community participants. In addition, a variety of continuous and discrete models of mania were compared in terms of their relative abilities to predict outcomes (i.e. health service utilization, internalizing and externalizing disorders, and suicidal behavior). RESULTS: Taxometric and ITLDM analyses consistently supported a continuous conceptualization of mania. In ITLDM analyses, a continuous model of mania demonstrated 6.52:1 odds over the best-fitting latent class model (LCM) of mania. Factor analyses suggested that the continuous structure of mania was best represented by a single latent factor. Predictive validity analyses demonstrated a consistent superior ability of continuous models of mania relative to discrete models. CONCLUSIONS: The present study provided three independent lines of support for a continuous conceptualization of mania. The implications of a continuous model of mania are discussed.


Assuntos
Transtorno Bipolar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Bipolar/classificação , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Escalas de Graduação Psiquiátrica , Análise de Regressão , Adulto Jovem
7.
Photochem Photobiol Sci ; 9(11): 1505-12, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20922251

RESUMO

Previous studies have shown that short-wavelength blue visible light induces retinal injury and may be a risk factor for age related macular degeneration. A2E is a blue light absorbing retinal chromophore that accumulates with age. Our previous in vitro studies have determined that, although A2E itself has a low phototoxic efficiency, the oxidation products of A2E that are formed in the presence of visible light can contribute to observed retinal pigment epithelial photodamage. The purpose of this study was to investigate the effects of blue light on retinal phototoxicity and its relationship to A2E, oxidized A2E and its isomers. Sprague-Dawley albino rats were dark adapted for 24 h. Control rats remained in the dark while experimental rats were exposed to blue light (λ = 450 nm, 3.1 mW cm(-2)) for 6 h. Isolated retinas were homogenized in Folch extraction mixture and then in chloroform. The dried extracts were reconstituted and divided for determination of organic soluble compound. Esters of fatty acids were determined with GC-MS, A2E and other chromophores using HPLC, and A2E oxidation products with LC-MS. Exposure of rat eyes to blue light did not significantly change the fatty acid composition of the retina. The A2E concentration (normalized to fatty acid content) in blue light exposed animals was found to be lower than the A2E concentration in control rats. The concentrations of all-trans-retinal-ethanolamine adduct and iso-A2E a precursor and an isomer of A2E respectively, were also lower after blue-light exposure than in the retinas of rats housed in the dark. On the other hand, the amount of oxidized forms of A2E was higher in the animals exposed to blue light. We conclude that in the rat eye, blue-light exposure promotes oxidation of A2E and iso-A2E to the products that are toxic to retinal tissue. Although high concentrations of A2E may be cytotoxic to the retina, the phototoxicity associated with blue light damage to the retina is in part a result of the formation of toxic A2E oxides. This effect may partially explain the association between blue light induced retinal injury and macular degeneration.


Assuntos
Modelos Animais de Doenças , Luz/efeitos adversos , Degeneração Macular/etiologia , Compostos de Piridínio/efeitos adversos , Retinoides/efeitos adversos , Animais , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Degeneração Macular/patologia , Masculino , Oxirredução , Compostos de Piridínio/metabolismo , Ratos , Ratos Sprague-Dawley , Retina/patologia , Retina/efeitos da radiação , Retinoides/metabolismo
8.
J Intellect Disabil Res ; 54(6): 501-15, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20426796

RESUMO

BACKGROUND: Variability in behaviour displayed by children with fragile X syndrome (FXS) may be partially attributable to environmental factors such as maternal responsivity. The purpose of this study was to explore variables associated with maternal behaviour during a task designed to elicit frustration in their children with FXS. METHODS: Forty-six mother-child dyads, in which the child had full-mutation FXS, were observed in their homes during a task designed to elicit frustration in the child. Each child was given a wrong set of keys and asked to open a box to retrieve a desired toy. Mothers were provided with the correct set of keys and instructed to intervene when they perceived their child was getting too frustrated. Child-expressed frustration and requests for help and maternal behaviours (comforting, negative control, and encouraging/directing) were observed and coded. Maternal variables (e.g. depression, stress, education levels), child variables (e.g. autistic behaviours, age, medication use) and child behaviours (frustration, requests for help) were explored as predictors of maternal behaviour. RESULTS: Almost all mothers intervened to help their children and most used encouraging/directing behaviours, whereas very few used comforting or negative control. Child age and child behaviours during the frustrating event were significant predictors of encouraging/directing behaviours in the mothers. Children whose mothers reported higher depressive symptomology used fewer requests for help, and mothers of children with more autistic behaviours used more negative control. CONCLUSIONS: The results of this study suggest that child age and immediate behaviours are more strongly related to maternal responsivity than maternal traits such as depression and stress.


Assuntos
Síndrome do Cromossomo X Frágil/psicologia , Comportamento de Ajuda , Relações Mãe-Filho , Poder Familiar/psicologia , Adulto , Afeto , Transtorno Autístico/diagnóstico , Transtorno Autístico/psicologia , Criança , Pré-Escolar , Depressão/diagnóstico , Depressão/psicologia , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Humanos , Estudos Longitudinais , Masculino , Comportamento Materno
9.
Psychol Med ; 39(7): 1087-96, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18845012

RESUMO

BACKGROUND: Taxometric research on depression has yielded mixed results, with some studies supporting dimensional solutions and others supporting taxonic solutions. Although supplementary tests of construct validity might clarify these mixed findings, to date such analyses have not been reported. The present study represents a follow-up to our previous taxometric study of depression designed to evaluate the relative predictive validities of dimensional and categorical models of depression. METHOD: Two sets of dimensional and categorical models of depression were constructed from the depression items of the Composite International Diagnostic Interview: (1) empirically derived models obtained using latent structure analyses and (2) rationally selected models, including an additive depressive symptoms scale (dimensional) and DSM major depressive episodes (categorical). Both sets of dimensional and categorical models were compared in terms of their abilities to predict various clinically relevant outcomes (psychiatric diagnoses and impairment). RESULTS: Factor analyses suggested a two-factor model ('cognitive-affective' and 'somatic' symptoms) and latent class analyses suggested a three-class model ('severe depression', 'moderate depression' and 'cognitive-affective distress'). In predictive analyses that simultaneously included dimensional and categorical models as predictors, the dimensional models remained significant unique predictors of outcomes while the categorical models did not. CONCLUSIONS: Both dimensional models provided superior predictive validity relative to their categorical counterparts. These results provide construct validity evidence for the dimensional findings from our previous taxometric study and thus inspire confidence in dimensional conceptualizations of depression. It remains for future research to evaluate the construct validity of the taxonic solutions reported in the literature.


Assuntos
Depressão/diagnóstico , Depressão/epidemiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Modelos Psicológicos , Estudos Transversais , Depressão/classificação , Depressão/psicologia , Transtorno Depressivo/classificação , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Análise Fatorial , Inquéritos Epidemiológicos , Humanos , Entrevista Psicológica , Modelos Estatísticos , Qualidade de Vida/psicologia , Análise de Regressão , Reprodutibilidade dos Testes
10.
Vet Parasitol ; 138(3-4): 308-17, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16516388

RESUMO

Lambs grazing certain legumes have reduced parasite intensities compared to lambs grazing ryegrass swards. Eighteen replicates of white clover (cv. AberHerald), lucerne (cv. Luzelle), red clover (cv. Merviot) and perennial ryegrass (cv. Abersilo) were sown at equivalent field rates in 25 cm diameter PVC pots and maintained outside for 6 months. On day 0, forage in each pot was cut to 50 mm from soil level and the pots were placed in a glasshouse (at 19-25 degrees C and 70% humidity) in a randomised block design. Ten grams sheep faeces containing 2,133 Haemonchus contortus eggs per gram were placed on the soil in each pot. Six replicates of each forage were destructively sampled on days 14, 21 and 29. Forage samples were cut at 50 mm from the soil surface and at the soil surface to give two samples per pot. The number of nematodes was determined by a modification of the Whitehead tray method. The ratio of free-living to infective-stage larvae was determined from at least 10% of the larvae. The number of H. contortus larvae kgdrymatter(-1) (DM) forage was calculated and the data rank transformed prior to analysis by ANOVA. There were fewer larvae on legumes compared with ryegrass on samples from forage above 50 mm (P<0.001) but there was no forage effect on larvae below this height. The sum of larvae present on all forage per kilogram DM showed fewer larvae on red clover compared with ryegrass on day 21 (P<0.05). There was an effect of day on the total number of larvae on forage (P<0.001) but there were no foragexday interactions. Analysis of the data according to the leaf area above 50 mm from the soil surface confirmed these results, that there were fewer larvae on legume forages than ryegrass above this height (P<0.01). Overall, red clover affected the development of H. contortus and all legumes affected larval migration above 50 mm compared with ryegrass but survival of larvae was similar on all forages. Further work is needed to determine if these effects of legume forages would reduce the number of parasitic larvae ingested by livestock under field conditions.


Assuntos
Hemoncose/veterinária , Haemonchus/crescimento & desenvolvimento , Lolium/parasitologia , Medicago sativa/parasitologia , Doenças dos Ovinos/parasitologia , Trifolium/parasitologia , Migração Animal/fisiologia , Animais , Fezes/parasitologia , Hemoncose/parasitologia , Hemoncose/prevenção & controle , Umidade , Intestinos/parasitologia , Larva/crescimento & desenvolvimento , Folhas de Planta/parasitologia , Ovinos , Doenças dos Ovinos/prevenção & controle , Análise de Sobrevida , Temperatura
11.
J Intellect Disabil Res ; 49(Pt 9): 647-56, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16108982

RESUMO

BACKGROUND: Dopamine, a neurotransmitter involved in motor and cognitive functioning, can be non-invasively measured via observation of spontaneous blink rates. Blink rates have been studied in a number of clinical conditions including schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder with results implicating either hyper or hypo dopaminergic states. METHODS: This study examined spontaneous blink rate in boys with fragile X syndrome (FXS). Blink rates of boys (4-8 years old) with FXS (n = 6) were compared with those of age-matched typically developing boys (n = 6) during active and passive tasks. Blink rates (blinks per minute) for each task were compared between the two groups. Then, the relation between blink measures and core FXS-related features [problem behaviours, arousal, fmr 1 protein (FMRP)] were examined within the group of boys with FXS. RESULTS: Blink rate in boys with FXS was significantly higher than typically developing boys during passive tasks. Within the FXS group, there were significant correlations between blink rate and problem behaviours and physiological arousal (i.e. heart activity) but not with FMRP. CONCLUSIONS: Observed differences in spontaneous blink rate between boys with and without FXS and the relation between blink rate and physiological and behavioural measures in boys with FXS suggests that further work examining dopamine dysfunction as a factor in the pathophysiology of FXS may be warranted.


Assuntos
Piscadela/genética , Dopamina/fisiologia , Síndrome do Cromossomo X Frágil/genética , Nível de Alerta/fisiologia , Atenção/fisiologia , Piscadela/fisiologia , Criança , Transtornos do Comportamento Infantil/genética , Transtornos do Comportamento Infantil/fisiopatologia , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Masculino , Fenótipo , Valores de Referência , Estatística como Assunto
12.
Hum Reprod ; 19(6): 1357-63, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15105393

RESUMO

BACKGROUND: Elevated maternal serum levels of interleukin-2 soluble receptor-alpha (IL-2 sRalpha), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been associated with pregnancy loss. The aim of our study was to evaluate the predictive value of these cytokines in the outcome of early IVF pregnancies. METHODS: One hundred and fifty-nine consecutive IVF patients who were subsequently diagnosed to have a biochemical pregnancy (n = 23), a first-trimester miscarriage (n = 19) or a normal term delivery (n = 117) were included in this study. Serum was collected from the initial pregnancy test, 11 days after a day 3 embryo transfer, and all samples were analysed for IL-2 sRalpha, TNF-alpha and IFN-gamma by commercially available enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: IL-2 sRalpha levels were significantly higher in patients with an early pregnancy loss compared with patients with a normal term delivery (849.5 +/- 69.6 versus 693.5 +/- 31.2 pg/ml, P = 0.02), and a cut-off point of IL-2 sRalpha >1000 pg/ml predicted a poor pregnancy outcome (44.4 versus 22.7% pregnancy loss, IL-2 sRalpha >or=1000 versus IL-2 sRalpha <1000 pg/ml; P = 0.02). IFN-gamma-positive patients had twice the risk for poor IVF pregnancy outcome compared with IFN-gamma-negative subjects (40.8 versus 20.0%, respectively; P < 0.02), including a significantly lower implantation rate (37.6 +/- 0.05 versus 50.0 +/- 0.03%, respectively; P = 0.02). There was no difference in pregnancy outcome based upon serum levels, or the ability to detect the presence of TNF-alpha. No differences in levels of these cytokines were found based on the aetiology of the patients' infertility. CONCLUSIONS: Elevated maternal serum levels of IL-2 sRalpha and IFN-gamma as early as 11 days after embryo transfer are associated with poor IVF pregnancy outcome.


Assuntos
Fertilização in vitro , Interferon gama/sangue , Resultado da Gravidez , Adulto , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-2 , Concentração Osmolar , Valor Preditivo dos Testes , Gravidez , Prognóstico , Estudos Prospectivos , Receptores de Interleucina/sangue , Receptores de Interleucina/química , Solubilidade , Fator de Necrose Tumoral alfa/análise
13.
Photochem Photobiol ; 78(1): 88-92, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12929754

RESUMO

Hypericin is the ingredient used to standardize the popular over-the-counter antidepressant medication St. John's Wort. Because hypericin readily produces singlet oxygen and other excited state intermediates, it is a very efficient phototoxic agent in the eye that can potentially induce the development of the cataract photooxidative mechanism. Hypericin absorbs in the UV and visible ranges, binds to the lens crystallins (alpha, beta and gamma) and damages these proteins through a photooxidative mechanism. Effects were measured previously using fluorescence, UV and mass spectrometry. We report here two additional methods to monitor lens damage: (1) measuring focal length variability using a ScanTox instrument and (2) measuring protein leakage from the damaged lens. Because nonenzymic glycation results in free radical production, we chose to use elevated glucose concentrations as a convenient model for studying oxidative stress. To compare and contrast photooxidative damage against oxidative damage to the lens, we also measured the focal length variability and protein leakage induced by the presence of elevated glucose concentrations. We found that the total accumulated protein leakage was positively correlated (r = 0.9) with variability in focal length. Lenses treated with hypericin and irradiated with UVB had an increase in focal length variability as compared with the lenses that were only UVB-irradiated. Lenses without UVB irradiation had much lower focal length variability than irradiated lenses. For non-hypericin-treated lenses, UVB-irradiated lenses had a larger variability (4.58 mm) than the unirradiated lenses (1.78 mm). The lenses incubated in elevated glucose concentrations had a focal length variability (3.23 mm) equivalent to that of the unirradiated hypericin-treated lenses (3.54 mm). We conclude that photooxidative damage by hypericin results in changes in the optical properties of the lens, protein leakage and finally cataract formation. In contrast to this, high concentrations of glucose induced protein leakage but not changes in optical properties or the opacity associated with a cataract. This work provides further evidence that people should protect their eyes from intense sunlight when taking St. John's Wort.


Assuntos
Cristalino/efeitos da radiação , Luz , Microscopia Confocal/métodos , Estresse Oxidativo , Perileno/análogos & derivados , Animais , Antracenos , Catarata/patologia , Bovinos , Cristalino/citologia , Cristalino/patologia , Microscopia Confocal/instrumentação , Perileno/farmacologia , Proteínas/análise
14.
J Photochem Photobiol B ; 64(2-3): 136-43, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11744400

RESUMO

The human eye is constantly exposed to sunlight and artificial lighting. Therefore the eye is exposed to UV-B (295-320 nm), UV-A (320-400 nm), and visible light (400-700 nm). Light is transmitted through the eye and then signals the brain directing both sight and circadian rhythm. Therefore light absorbed by the eye must be benign. Damage to the young and adult eye by intense ambient light is avoided because the eye is protected by a very efficient antioxidant system. In addition, there are protective pigments such as the kynurenines, located in the human lens, and melanin, in the uvea and retina, which absorb ambient radiation and dissipate its energy without causing damage. After middle age there is a decrease in the production of antioxidants and antioxidant enzymes. At the same time, the protective pigments are chemically modified (lenticular 3-hydroxy kynurenine pigment is enzymatically converted into the phototoxic chromophore xanthurenic acid; melanin is altered from an antioxidant to pro-oxidant) and fluorescent chromophores (lipofuscin) accumulate to concentrations high enough to produce reactive oxygen species. We have known for some time that exposure to intense artificial light and sunlight either causes or exacerbates age-related ocular diseases. We now know many of the reasons for these effects, and with this knowledge methods are being developed to interfere with these damaging processes.


Assuntos
Traumatismos Oculares/etiologia , Luz Solar/efeitos adversos , Adulto , Animais , Humanos
15.
Photochem Photobiol ; 74(5): 740-4, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11723804

RESUMO

The tryptophan metabolite, xanthurenic acid (Xan), is produced through a transamination reaction in high concentrations in human lenses with age and has been isolated from aged human cataractous lenses. It has appreciable absorption between 300 and 400 nm (lambda max = 334 nm), the range absorbed by the human lens. Our recent studies have shown that unlike most tryptophan metabolites in the eye, Xan is photochemically active, producing both superoxide and singlet oxygen. To determine if Xan could act as a photosensitizer and photooxidize cytosolic lens proteins, alpha-, beta- and gamma-crystallins were irradiated (lambda > 300 nm, 12 mW/cm2) in the presence and absence of Xan. Upon irradiation and in the presence of Xan, lens proteins polymerized in the order alpha > beta > gamma as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Further analysis of the photolyzed alpha-crystallin by mass spectrometry indicated that histidine, tryptophan and methionine residues were oxidized at specific positions in a dose-dependent (irradiation time) manner. In alpha A-crystallin two forms of oxidized histidine 154 were observed, 2-imidazolone and 2-oxohistidine. Our results suggest that naturally occurring Xan is a chromophore capable of photosensitization and photooxidation of lens proteins. Furthermore, this compound could play a role in age-related cataractogenesis.


Assuntos
Catarata/induzido quimicamente , Cristalinas/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Xanturenatos/farmacologia , Cristalinas/química , Cristalinas/isolamento & purificação , Humanos , Cristalino/crescimento & desenvolvimento , Oxirredução , Fotólise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
J Speech Lang Hear Res ; 44(5): 1083-96, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11708529

RESUMO

This study examined changes in the complex syntax production of 85 3- and 4-year-old African American children and the role of child (i.e., gender, age, African American English) and family (i.e., home environment) factors. The mean percentage of utterances containing one or more complex syntax forms was 6.2% at 3 years and 11.7% at 4 years. Girls produced more complex syntax forms than did boys. Complex syntax production increased significantly between age 3 and age 4 and correlated positively with mean length of utterance in words. Children from more responsive and stimulating home environments produced more complex syntax at 4 years. African American English was not related to the amount of complex syntax used.


Assuntos
Linguagem Infantil , Idioma , Linguística , Pré-Escolar , Meio Ambiente , Feminino , Humanos , Masculino , Medida da Produção da Fala , Comportamento Verbal
17.
Dev Psychobiol ; 39(2): 107-23, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11568881

RESUMO

In this study, the relationship between physiological arousal, as indexed by heart rate variability, was examined in boys with fragile X syndrome (FXS) and typically developing boys matched on chronological age. In addition, the relationship of heart activity to clinical and molecular factors in the group of boys with FXS was examined. Results suggest that boys with FXS have higher levels of heart activity during the passive phases, as reflected in shorter heart periods. This high level of heart activity appears to be due to increased sympathetic activity and reduced parasympathetic activity. Boys with FXS did not display the expected patterns of heart activity in response to phases of increasing challenge, and sympathetic and parasympathetic systems did not appear coordinated in these boys with FXS. Clinical factors may be related to neural regulation of heart activity while molecular factors do not appear to be.


Assuntos
Nível de Alerta/fisiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Síndrome do Cromossomo X Frágil/complicações , Síndrome do Cromossomo X Frágil/fisiopatologia , Frequência Cardíaca/fisiologia , Proteínas de Saccharomyces cerevisiae , Antiporters , Doenças Cardiovasculares/diagnóstico , Pré-Escolar , Humanos , Masculino
18.
Am J Ment Retard ; 106(3): 216-30, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11389664

RESUMO

We prospectively examined the developmental trajectories of receptive and expressive communication skills of 39 young males, 20 to 86 months of age, with fragile X syndrome. Eight showed features characteristic of autism. Children were tested one to three times using a standardized language test. They showed marked delays in language development, but substantial individual variability. Participants acquired expressive language skills more slowly than receptive language over time, gaining receptive language at about half the rate expected for typically developing children and expressive language at one third the rate. Both cognitive skills and autistic characteristics of the young males with fragile X syndrome related to receptive and expressive communication development, but neither predicted the discrepancies between expressive and receptive language acquisition over time.


Assuntos
Comunicação , Síndrome do Cromossomo X Frágil/psicologia , Comportamento Verbal , Criança , Transtornos Cognitivos/etiologia , Deficiências do Desenvolvimento/diagnóstico , Síndrome do Cromossomo X Frágil/complicações , Humanos , Transtornos da Linguagem/diagnóstico , Masculino
19.
Pediatrics ; 107(5): 1037-42, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11331683

RESUMO

OBJECTIVE: This study examined whether otitis media with effusion (OME) and associated hearing loss during the first 4 years of life were related to the ratings of parents, teachers, and clinicians of children's attention and behavior in the first 6 years of life. METHODS: In a prospective study, 85 black children were recruited from community-based child care programs when they were between 6 and 12 months old. OME and hearing status were monitored repeatedly from 6 months to 4 years old. Measures of attention and behavior were collected from parents, teachers, and clinicians when the children were infants, preschoolers, and first graders. RESULTS: On average, children experienced either bilateral or unilateral OME 30% of the time and hearing loss 19.9% of the time between 6 months and 4 years old. Descriptive and inferential analyses revealed no significant associations between OME or hearing loss and the measures of attention or behavior completed by parents, teachers, and clinicians. CONCLUSIONS: In this sample of children, there was no relationship between amount of early childhood OME or hearing loss and measures of attention or behavior in the first 6 years of life as reported by parents, teachers, and clinicians.otitis media, hearing, attention, behavior.


Assuntos
Atenção , Comportamento Infantil , Surdez/complicações , Otite Média com Derrame/complicações , Criança , Transtornos do Comportamento Infantil/diagnóstico , Transtornos do Comportamento Infantil/etiologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Análise Multivariada , Estudos Prospectivos , Testes Psicológicos , Análise de Regressão , Inquéritos e Questionários
20.
Am J Psychiatry ; 158(5): 725-30, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11329393

RESUMO

OBJECTIVE: Each of 10 published studies investigating the relationship between HIV infection and risk for depressive disorders concluded that HIV-positive individuals are at no greater risk for depression than comparable HIV-negative individuals. This study used meta-analytic techniques to further examine the relationship between depressive disorders and HIV infection. METHOD: Meta-analytic techniques were used to aggregate and reanalyze the data from 10 studies that compared HIV-positive and HIV-negative individuals for rates of major depressive disorder (N=2,596) or dysthymic disorder (N=1,822). RESULTS: The frequency of major depressive disorder was nearly two times higher in HIV-positive subjects than in HIV-negative comparison subjects. On the other hand, findings were inconclusive with regard to dysthymic disorder. Rates of depression do not appear to be related to the sexual orientation or disease stage of infected individuals. CONCLUSIONS: Although the majority of HIV-positive individuals appear to be psychologically resilient, this meta-analysis provides strong evidence that HIV infection is associated with a greater risk for major depressive disorder. Future research should focus on identifying pathways of risk and resilience for depression within this population.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Transtorno Depressivo/epidemiologia , Infecções por HIV/epidemiologia , Bissexualidade/estatística & dados numéricos , Comorbidade , Intervalos de Confiança , Transtorno Distímico/epidemiologia , Feminino , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Homossexualidade Feminina/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Razão de Chances , Risco , Fatores de Risco
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