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PURPOSE: Childhood abuse is associated with an increased risk of developing eating disorders (EDs) as well as personality disorders (PDs). However, their interaction is still uncertain, particularly in adolescents. This study investigates the correlations between childhood emotional neglect (CEN), childhood emotional abuse (CEA), and obsessive-compulsive and borderline personality styles in female adolescent inpatients with eating disorders (EDs). METHODS: One hundred and twenty-eight inpatients (ages 14-18) were assessed, 54 were diagnosed with restricting-type anorexia nervosa (AN-R) and 33 with a binge-purging ED [BP-ED; comprising patients with binge-purging type anorexia nervosa (AN-BP), n = 15, and bulimia nervosa (BN), n = 18]. Fifty healthy participants made up the control group (CG). CEN and CEA were assessed with the Childhood Trauma Questionnaire, while the Personality Style and Disorder Inventory was implemented to determine personality styles. RESULTS: A MANOVA revealed a significant main effect of CEA on spontaneous-borderline personality style [F(8,119) = 17.1, p < 0.001, η2 = 0.126], as well as a main effect of ED group on spontaneous-borderline [F(2,119) = 3.1, p = 0.048, η2 = 0.050]. A significant interaction between ED group, CEA, and spontaneous-borderline was found [F(2,119) = 3.5, p = 0.034, η2 = 0.055] with BP-ED showing significantly higher scores in CEA (9.3 ± 4.0) and in spontaneous-borderline (14.2 ± 6.2). CONCLUSIONS: Considering CEA and borderline personality style in adolescent inpatients with BN or AN-BP may help improve the understanding of the etiology and maintenance of BP-ED and provide more effective treatment targets. LEVEL OF EVIDENCE: Level III, case-control analytic study.
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Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Anorexia Nervosa/psicologia , Bulimia Nervosa/psicologia , Criança , Abuso Emocional , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Feminino , Humanos , Pacientes Internados , PersonalidadeRESUMO
BACKGROUND: Children in migration experience various forms of violence before, on, and after their migration journey. Epidemiological research on the prevalence of violence in this highly vulnerable group is lacking, however. METHOD: A PRISMA-guided systematic literature review with a three-tiered search strategy was conducted by searching academic literature databases and gray literature on websites of international organizations and by contacting experts. All empirical studies published within the last 15 years were eligible. Predefined search terms related to violence, children, epidemiology, and migration were used. FINDINGS: Of 1014 records, 17 studies met the inclusion criteria. Sample sizes ranged from 100 to 8,047, with a total of 16,915 children (Mdn = 311). Lifetime prevalence of violence varied considerably: Child physical maltreatment ranged from 9 %-65 % and child sexual abuse from 5 %-20 %. For internally displaced children, violence often occurred at the hands of those who were responsible for their care. Unfortunately, data on the context and country in which the violence occurred-in the country of origin, on route, or in the country of arrival-were lacking. CONCLUSION: The discrepancy between the importance of the topic and the dearth of data is striking. Filling the gaps requires not only more rigorous methodology but also more research in general on the epidemiology of violence against children in migration. We outline methodological challenges and draft an agenda for improved data on the topic. There is an urgent need for evidence that supports the development and adaptation of effective, tailored, and child-sensitive prevention and intervention programs for children in migration.
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Migrantes/estatística & dados numéricos , Violência/estatística & dados numéricos , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Humanos , Prevalência , Refugiados/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Populações Vulneráveis/estatística & dados numéricosRESUMO
Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae. Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19±5% and 26±4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-ß-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98±64%), electrical time constant (by 285±149%), and lipid recruitment to the bilayer (by 84±39%). Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance.
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Cavéolas/fisiologia , Sistema de Condução Cardíaco , Miócitos Cardíacos/fisiologia , Potenciais de Ação , Animais , Caveolina 3/genética , Caveolina 3/metabolismo , Células Cultivadas , Ventrículos do Coração/citologia , Mecanotransdução Celular , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/ultraestrutura , Técnicas de Patch-Clamp , Sarcolema/metabolismo , Função Ventricular , Pressão VentricularRESUMO
OBJECTIVE: Patients with anorexia nervosa (AN) exhibit high rates of psychiatric comorbidity. To disentangle the effects of duration of illness on comorbid psychiatric symptoms, we investigated the rates of comorbid psychiatric disorders, suicidality and self-harm behaviour in adolescent patients with a first onset of AN. METHODS: In adolescent females (n = 148) with a first onset of AN, body mass index, psychiatric comorbidity (according to DSM-IV), depressive symptoms, suicidality and self-injurious behaviour were assessed. RESULTS: Seventy patients (47.3%) met the criteria for at least one comorbid psychiatric disorder. The binge-purging subtype was associated with increased rates of psychiatric comorbidity, suicidality and self-injurious behaviour. The severity of eating disorder-specific psychopathology influenced current psychiatric comorbidity and suicidal ideation. CONCLUSION: Prevalence rates of comorbid psychiatric disorders and suicidal ideation are considerably lower among adolescents with AN compared with adults. An early and careful assessment, along with adequate treatment of the eating disorder, might prevent the development of severe psychiatric comorbidities.
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Anorexia Nervosa/epidemiologia , Transtornos Mentais/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Adolescente , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Índice de Massa Corporal , Comorbidade , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Prevalência , Comportamento Autodestrutivo/diagnóstico , Comportamento Autodestrutivo/psicologia , Ideação Suicida , Suicídio/psicologiaRESUMO
OBJECTIVE: Several studies have revealed impairments in cognitive functions among patients with affective disorders (AD). However, to date there are few neuropsychological studies on cognitive flexibility among adolescent patients with AD, especially on gender differences in AD. Here, we investigate cognitive functions, especially cognitive flexibility, in adolescent patients with unipolar AD (UAD) compared to a healthy control group (CG). METHOD: The study population consists of 17 male patients (M
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Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Função Executiva , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Adolescente , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Psicometria , Tempo de Reação , Valores de Referência , Fatores SexuaisRESUMO
For studies on the aryl hydrocarbon receptor (AhR)-dependent toxicity of the mycotoxins alternariol (AOH) and alternariol methyl ether (AME), three mouse hepatoma (Hepa-1) cell lines with intact and with compromised AhR signaling were compared with respect to their activities for hydroxylation, methylation, and glucuronidation. Whereas the activities of cytochrome P450-mediated monooxygenase and catechol-O-methyl transferase were very low and did not differ between the three cell lines, a pronounced difference was observed for UDP-glucuronosyl transferase activity, which was much higher in Hepa-1c1c4 than in c1c7 and c1c12 cells. In all three cell types, the rate of glucuronidation of AOH was about four times higher than that of AME. Whereas AME caused a concentration-dependent G2/M arrest in each cell line, AOH arrested Hepa-1c1c7 and c1c12 cells but not c1c4 cells. However, Hepa-1c1c4 cells were arrested by AOH when ß-glucuronidase was added to the incubation medium in order to reverse the formation of AOH glucuronides. We conclude that the failure of AOH to cause cell cycle inhibition in Hepa-1c1c4 cells is due to its efficient glucuronidation. The considerable UDP-glucuronosyl transferase activity of Hepa-1c1c4 cells should be taken into account when other compounds are studied in this cell line. Moreover, we demonstrate that differences in glucuronide formation between cell types can be overcome by the addition of ß-glucuronidase to the cell culture medium.
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Carcinoma Hepatocelular/metabolismo , Glucuronídeos/metabolismo , Hepatócitos/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Catecol O-Metiltransferase/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Quimioterapia Combinada , Glucuronidase/farmacologia , Glucuronosiltransferase/metabolismo , Hepatócitos/efeitos dos fármacos , Lactonas/toxicidade , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Micotoxinas/toxicidade , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Transdução de SinaisRESUMO
Many young women and also men are constantly dissatisfied with their body. In some cases the discontent with one's own body and the resulting restrictive eating behaviour can predetermine the path to bulimia nervosa. This article summarizes the treatment options and their respective evidence for bulimia nervosa. Apart from the choice of treatment setting, psychotherapeutic treatment measures and the role of psychopharmacologic drugs for the treatment of bulimia nervosa are discussed.
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Bulimia Nervosa/terapia , Adolescente , Adulto , Imagem Corporal , Bulimia Nervosa/diagnóstico , Bulimia Nervosa/psicologia , Doença Crônica , Terapia Cognitivo-Comportamental/métodos , Terapia Combinada , Comorbidade , Dieta Redutora/psicologia , Feminino , Humanos , Masculino , Prognóstico , Psicoterapia/métodos , Psicotrópicos/uso terapêutico , Fatores de Risco , Adulto JovemRESUMO
The purpose of this study was to develop an instrument (Test for Body Image Distortion in Children and Adolescents, BID-CA) suitable for adolescents to detect and quantify body image distortion. Participants were patients with anorexia nervosa (AN; N=75), healthy age-matched control participants (N=268) and age-matched thin female athletes (N=50) with a mean age of 15.2 (standard deviation =2.0) years. We assessed body image distortion (arm, waist, and thigh) using the BID-CA and two scales of the Eating Disorder Inventory-2 (EDI-2; Drive for Thinness, Body Dissatisfaction). Diagnostic validity of the BIDCA was analyzed with receiver operating characteristic (ROC) curves. Additional regression analyses revealed the variables BID-CA thigh and EDI-2 Drive for Thinness to be the best at predicting body image distortion among AN patients. In conclusion, the BID-CA showed good diagnostic validity. It is efficient, language independent, time-saving and seems appropriate for children and adolescents.
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Anorexia Nervosa/psicologia , Imagem Corporal , Testes Psicológicos , Adolescente , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/terapia , Tamanho Corporal , Estudos de Casos e Controles , Criança , Feminino , Humanos , Modelos Logísticos , Análise por Pareamento , Análise Multivariada , Psicoterapia , Curva ROC , Valores de Referência , Reprodutibilidade dos Testes , Resultado do Tratamento , Adulto JovemRESUMO
Alternariol (AOH) and alternariol-9-methyl ether (AME) are major toxins produced by fungi of the genus Alternaria and are frequently found in various food items. Because AOH has three hydroxyl groups and AME two, the formation of various glucuronides must be expected. When AOH was incubated with hepatic and intestinal microsomes from rats, pigs and humans in the presence of uridine diphosphate glucuronic acid, two glucuronides were detected and tentatively identified as AOH-3-O-glucuronide and AOH-9-O-glucuronide. Under the same conditions, AME yielded predominantly AME-3-O-glucuronide and only small amounts of AME-7-O-glucuronide. The activities of all microsomes for the glucuronidation of AOH and AME were in the same range. Nine out of ten recombinant human UDP-glucuronosyltransferases (UGTs) were able to glucuronidate AOH, and eight out of ten UGTs had activity for AME. These data suggest that AOH and AME are readily glucuronidated in hepatic and extrahepatic tissues, implying that glucuronidation constitutes a major metabolic pathway in the disposition of these mycotoxins.
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OBJECTIVE: To compare general and eating disorder-specific psychopathology in patients with acute anorexia nervosa (acAN), weight-recovered patients (recAN) and healthy control women (HCW). METHODS: One hundred anorexia nervosa patients (66 acAN and 34 recAN) and 88 HCW were included in our study. Psychopathology was assessed by self-report questionnaires [Symptom Check List 90 Revised (SCL-90-R), Eating Disorder Inventory-2 (EDI- 2)] as well as by interview [Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX)] and compared using multivariate analysis of variance. Plasma leptin levels were determined using enzyme linked immunosorbent assay. RESULTS: Mean comparisons indicated highly significant differences between acAN and recAN subjects on all psychopatholgy variables, except for perfectionism. RecAN subjects did not differ from HCW. Partial weight recovery was associated with decreasing levels of psychopathology. Correlational analyses suggested strong negative associations between leptin levels and psychopathology. CONCLUSION: Prolonged malnutrition, as indicated by suppressed plasma leptin levels, is strongly related to eating disorder-specific as well as general psychopathological symptoms. Weight recovery is associated with the absence of psychopathology. These data emphasize the interaction between somatic and psychological variables.
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Anorexia Nervosa/psicologia , Peso Corporal , Magreza/psicologia , Adaptação Psicológica , Adolescente , Adulto , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Entrevista Psicológica , Leptina/sangue , Análise Multivariada , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: Central serotonergic pathways may play an important role in the etiology of anorexia nervosa (AN). Although platelet monoamine oxidase activity (MAO-B) has been proposed as an index of cerebral serotonin activity, studies in patients with AN are scarce. METHODS: Platelet MAO-B activity was determined in 59 acutely underweight AN patients (acAN, aged 14-29 years, BMI=15.2+/-1.4), 35 weight-recovered AN patients (recAN, aged 15-29, BMI=20.8+/-2.2) and 59 healthy control women (HCW, aged 14-26, BMI=21.6+/-2.1). Plasma leptin served as an indicator of malnutrition. Results were compared by ANCOVA controlling for confounding variables. RESULTS: Platelet MAO-B activity in acAN patients (5.2+/-1.4 nmol/10 (9)pltx15 min) was similar to HCW (5.5+/-1.9) but significantly lower in recAN patients (4.4+/-1.5). BMI and leptin showed a significant negative correlation with MAO-B activity in AN patients, but not in HCW. DISCUSSION: Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Whether low MAO-B activity in weight-recovered AN patients indicates a premorbid trait or a secondary change due to recovery remains to be elucidated.
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Anorexia Nervosa/enzimologia , Plaquetas/enzimologia , Monoaminoxidase/sangue , Magreza/enzimologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adolescente , Adulto , Peso Corporal/fisiologia , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Feminino , Gônadas/fisiologia , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Leptina/sangue , Fenômenos Fisiológicos da Nutrição , Escalas de Graduação Psiquiátrica , Serotonina/metabolismo , Magreza/etiologia , Adulto JovemRESUMO
OBJECTIVES: The aim of the present study was to ascertain whether the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) is applicable for use with adolescents. Furthermore, the diagnostic concordance between SCID-II and the clinicians' estimations of personality disorders (PD) is assessed. In addition, we identified predicting factors for personality disorders in adolescent psychiatric inpatients. METHODS: 110 adolescent psychiatric inpatients aged 14-18 years were assessed by means of SCID-II and a personality and disorder inventory (PSSI). RESULTS: 32.7% of the inpatients met the criteria for PD according to SCID-II. While agreement between the presence of any PD based on SCID-II and that found according to clinicians' estimations was low, moderate and very good agreement between SCID-II and clinicians' estimations was found with regard to borderline PD and histrionic PD. Logistic regression analyses identified "anorexia nervosa (binge-purging)", "attention-deficit/hyperactivity disorder/conduct disorder (ADHD/CD)" and "socioeconomic status" as good predictors for PD. CONCLUSIONS: The SCID-II - which was primarily developed for use with adults - is suitable for use among adolescents. Anorexia nervosa (binge-purging type) and ADHD/CD are closely associated with the development of PD in adolescents.
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Determinação da Personalidade/estatística & dados numéricos , Transtornos da Personalidade/diagnóstico , Adolescente , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/psicologia , Anorexia Nervosa/terapia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Alemanha , Hospitalização , Humanos , Entrevista Psicológica , Masculino , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Transtornos do Humor/terapia , Transtornos da Personalidade/psicologia , Transtornos da Personalidade/terapia , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/psicologia , Transtornos Somatoformes/terapiaRESUMO
OBJECTIVE: The current study determined the unconfined compressive modulus of tissue-engineered constructs with varying sulfated glycosaminoglycan (GAG) density produced by goat articular chondrocytes in type II collagen scaffolds prepared with a range of cross-link densities and various times in culture. The purpose of this work is to establish a basis for future studies employing constructs of selected maturity (e.g., 25%, 50%, or 75% normal GAG content) for cartilage repair in vivo. METHODS: Porous scaffolds (8 mm diameter by 2 mm thick) were fabricated from porcine type II collagen by freeze-drying, followed by dehydrothermal treatment and carbodiimide cross-linking. In a pilot study, passage 3 adult caprine articular chondrocytes isolated from one goat were grown in scaffolds with six cross-link densities for 2, 3, 4, and 6 weeks (n=3). The goal was to select scaffold cross-link densities and times in culture that would produce constructs with approximately 25%, 50% and 75% the GAG density of native articular cartilage. Based on the results of the pilot study, chondrocytes from three goats were grown in scaffolds with two cross-link densities for three time periods: 3, 5, and 9 weeks (n=6; one of the cross-link groups was run in quadruplicate). The equilibrium modulus from unconfined compression testing of these samples was correlated with GAG content. RESULTS: There was a notable increase in GAG density with decreasing cross-link density. Histological analysis verified a chondrogenic phenotype and revealed various amounts of GAG and type II collagen-containing cartilage. The correlation between modulus and GAG density had a linear coefficient of determination of 0.60. One group with a mean GAG density of 22 microg/mm(3), which was 140% the GAG density of normal caprine articular cartilage, averaged a compressive modulus of 31.5 kPa, which was 10% of caprine articular cartilage tested in this study. CONCLUSIONS: The GAG density and modulus of tissue-engineered constructs can be controlled by the degree of cross-linking of type II collagen scaffolds and time in culture.
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Cartilagem/metabolismo , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Força Compressiva/fisiologia , Glicosaminoglicanos/metabolismo , Engenharia Tecidual/métodos , Animais , Células Cultivadas , Cabras , Estatística como Assunto , Estresse Mecânico , SuínosRESUMO
TheAlternaria toxins alternariol (AOH), alternariol-9-methyl ether (AME), altenuene (ALT) and isoaltenuene (iALT) undergo extensive oxidative metabolism, but the cytochrome P450 (CYP) isoforms responsible for the reported hydroxylation reactions are yet unknown. In the present study, the activities of twelve human CYP isoforms for the hydroxylation of AOH, AME, ALT and iALT at different positions have been determined. The most active monooxygenase for AOH and AME was CYP1A1, and lower activities were observed for CYP1A2, 2C19 and 3A4. Hydroxylation at C-2 of AOH and AME was the preferred reaction of most isoforms. For ALT and iALT, CYP2C19 had the highest activity, followed by 2C9 and 2D6. The dominating metabolite of all active isoforms was the 8-hydroxylated ALT and iALT. The activities of the CYP isoforms are consistent with the pattern of metabolites of theAlternaria toxins obtained with pooled human hepatic microsomes. Based on the activities of the CYP isoforms, a significant extrahepatic hydroxylation must be expectede.g. in the lung and esophagus for AOH and AME, and in the intestine and ovaries for ALT and iALT. As all major hydroxylation products are catechols, the extrahepatic metabolism ofAlternaria toxins may be of toxicological relevance.
RESUMO
Treatment, for 1 h, of cultured Chinese hamster V79 cells, human liver HepG2 cells, and human colon HT-29 cells with theAlternaria toxins alternariol (AOH) and alternariol methyl ether (AME) caused a concentration-dependent induction of DNA strand breaks at concentrations ranging from 5 to 50 micromolar. After treatment for 24 h, DNA strand breaks were observed in HepG2 but not HT-29 cells. Analysis of the 24 h-incubation media of HT-29 cells showed that both toxins were completely conjugated, whereas 75% were still present as unconjugated compounds in the 24 h-media of HepG2 cells. Lysates of both cell types fortified with UDPGA were found to convert both toxins into two glucuronides each, but HT-29 cells exhibited a much high activity than HepG2 cells and gave rise to a different ratio of glucuronides. It is concluded that glucuronidation eliminates the DNA strandbreaking potential of AOH and AME, and that the two glucuronides of eachAlternaria toxin are generated by different UGT isoforms.
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OBJECTIVE: To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD). METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were over age 50 with a diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores between 12 and 25. Subjects were treated with idebenone 120, 240, or 360 mg tid, each of which was compared with placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Subcomponent (ADAS-Cog) and a Clinical Global Impression of Change (CGIC). Secondary outcome measures included measurements of activities of daily living, the Behavioral Pathology in Alzheimer's Disease Rating Scale, and the MMSE. RESULTS: Five hundred thirty-six subjects were enrolled and randomized to the four groups. Except for a slight difference in age, there were no differences in patient characteristics at baseline. For the primary outcome measures, there were no significant overall differences between the treatment groups in the prespecified four-group design. In an exploratory two-group analysis comparing all three treated groups combined with placebo, drug-treated patients performed better on the ADAS-Cog in both the intent-to-treat (ITT) and completers analyses. There were no differences in the CGIC scores for the ITT or completers analyses in either the four-group or the two-group analyses. There were no overall differences on any of the secondary outcome measures in any of the analyses. CONCLUSION: Idebenone failed to slow cognitive decline in AD that was of sufficient magnitude to be clinically significant.
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Doença de Alzheimer/tratamento farmacológico , Benzoquinonas/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Idoso , Doença de Alzheimer/diagnóstico , Benzoquinonas/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Ubiquinona/análogos & derivadosRESUMO
Se analizan en forma retrospectiva los resultados alejados del tratamiento quirúrgico de 159 pacientes intervenidos por una fístula anorrectal en un período de 10 años, el 80 por ciento varones y el 77 por ciento entre 31 y 60 años de edad, con un seguimiento promedio de 64 meses (extremos 26-151). El 12 por ciento de las fístulas era recidivada y el 25 por ciento mostraba algún factor de complejidad distinto del compromiso del aparato esfinteriano. El trayecto fistuloso era superficial en el 11 por ciento de los casos, interesfintérico en el 35 por ciento y transesfintérico en el 47 por ciento. Hubo recidiva en 8 pacientes (5 por ciento) entre 8 meses y 5 años, lo que fue independiente de la identificación intraoperatoria del orificio fistuloso interno. En 22 casos (13,8 por ciento) se pesquisó algún grado de disturbio de la continencia, 4 de ellos con incontinencia mayor según la clasificación de Williams. Se encontró una asociación estadísticamente significativa entre las variables incontinencia y sexo (p= 0.009) con una razón de disparidad de 3,4; entre la incontinencia y el tipo de técnica quirúrgica (p= 0,008) con una razón de disparidad de 8,6 entre el colgajo mucoso y la técnica del sedal cortante con banda elástica. Al comparar las fístula sin compromiso del esfínter voluntario con aquellas de trayecto transesfintérico, la asociación existió en el límite (p= 0,43 con una razón de disparidad de 2,9). Paradójicamente la fistulectomía presenta un menor riesgo de incontinencia que la fistulotomía en fístula de complejidad comparable, aunque el período de cicatrización es mayor. La técnica del colgajo mucosos utilizada en fístulas complejas y recidivadas muestra la mayor incidencia de transtornos de la continencia. La técnica del sedal cortante preferentemente en fístula altas aparece como la técnica segura, reproducible y eficiente (recidiva del 2 por ciento, incontinencia global del 9 por ciento) y nos parece de elección en todo paciente con algún riesgo de incontinencia
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Humanos , Masculino , Adolescente , Adulto , Feminino , Pessoa de Meia-Idade , Fístula Retal/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Distribuição por Idade , Incontinência Fecal , Recidiva , Estudos Retrospectivos , Distribuição por Sexo , Retalhos CirúrgicosRESUMO
The presented work investigates the mutagenicity of seawater with regard to its distribution along the German Baltic Sea coastline. Further on in this paper the relationship between mutagenic activity and certain chemical, microbiological and physical parameters is analysed. Water samples were drawn from eight places between Eckernförde and Ribnitz-Damgarten. Seawater was concentrated using XAD-2/7 resin. Extracts of up to 3-l per plate were tested with the Salmonella mutagenesis assay employing the strains TA 98 and TA 100 with and without addition of S9-mixture for metabolic activation. Samples from Weissenhaus, Travemünde and Wismar demonstrated a mutagenic activity with the strain TA 98. Tested filter sediment was not mutagenic. The sum of six polycyclic aromatic hydrocarbons (PAH) concentrated by XAD resin and obtained by high performance liquid chromatography (HPLC) were between 0.03 and 34.11 ng/l seawater. No correlation of measured mutagenicity and chemical or physical parameters could be established. The sampling place Wismar with one mutagenic sample had the highest number of colony forming units of Escherichia coli.
Assuntos
Escherichia coli/crescimento & desenvolvimento , Mutagênicos/toxicidade , Salmonella/efeitos dos fármacos , Água do Mar/análise , Poluentes Químicos da Água/toxicidade , Cromatografia Líquida de Alta Pressão , Contagem de Colônia Microbiana , Alemanha , Testes de Mutagenicidade/métodos , Mutagênicos/análise , Resinas Vegetais , Água do Mar/química , Água do Mar/microbiologia , Microbiologia da Água , Poluentes Químicos da Água/análiseRESUMO
This paper reviews data reported in the literature as well as recent and unpublished studies from our laboratory on the metabolism and genotoxicity of the xenobiotic growth promoters 17beta-trenbolone, melengestrol acetate and zeranol. In our metabolic study, the oxidative in vitro metabolites generated by hepatic microsomes from rats, bovine and humans were analyzed by HPLC and GC/MS. 17beta-Trenbolone gave rise to at least 13 monohydroxylated products, whereas 12 mono- and dihydroxylated metabolites were obtained with melengestrol acetate and at least 5 with zeranol. The genotoxic potential of the parent compounds was studied using the following endpoints: induction of HPRT mutations in cultured V79 cells and of lacI mutations in E. coli; induction of micronuclei in V79 cells; and formation of DNA adducts in cultured primary rat hepatocytes. Negative results were obtained in most of these assay systems. Only the micronucleus induction was marginally positive with 17beta-trenbolone and zeranol at near-cytotoxic concentrations. Commercial melengestrol acetate was found to contain an impurity causing apoptosis in V79 cells. The genotoxic potential of the numerous oxidative metabolites of the xenobiotic growth promoters remains to be studied.
Assuntos
Acetato de Melengestrol/metabolismo , Mutagênicos/metabolismo , Acetato de Trembolona/metabolismo , Zeranol/metabolismo , Animais , Humanos , Acetato de Melengestrol/química , Mutagênicos/química , Acetato de Trembolona/química , Zeranol/químicaRESUMO
Anorexia nervosa is an eating disorder that may be accompanied by cardiac symptoms of varying severity. So far disturbances like arrhythmias, mitral valve prolapse and loss of cardial ventricle mass have been described. Other somatic complications consist of electrolyte and acid-base imbalances, which in turn influence cardiac function. Between 1990 and 1999 we observed ten case reports from inpatient anorexic female adolescents, who developed pericardial effusions in the course of their illness. The diagnosis and course was revealed by echocardiography. No signs of heart failure could be noticed. In eight patients pericardial effusion remitted completely or partly by a concurrent increase in weight. A distinct pathophysiology for the development of pericardial effusion could not be revealed, but a correlation to restoration of weight seems to exist. Our report suggests that pericardial effusions are more frequent cardiac complications in anorexia nervosa than previously known. In most cases the clinical significance is doubtful.