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1.
Nord J Psychiatry ; 64(3): 196-202, 2010 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-19919290

RESUMO

BACKGROUND: Shame is an acknowledged part of several psychopathological conditions, but is underrepresented in clinical research. Cook's Internalized Shame Scale (ISS) is the most promising measure, but has mostly been used for testing small clinical samples biased toward depressive pathology and female participants. AIMS: To contribute to establishing indicators of pathological shame in outpatients with depression and anxiety disorder, and to contribute to establishing norms for the ISS in Scandinavia. METHOD: The ISS was administered to n = 200 gender balanced non-patient and outpatient samples. A total of 100 patients each were diagnosed as suffering from a depression or anxiety disorder. The diagnoses were supported by Beck's Depression (BDI) and Anxiety Inventory (BAI). The analyses used were the principal component analysis (PCA) and confirmatory factor analysis (CFA) for item structure and sample equivalence, ANOVAs, t-tests and Mann-Whitney non-parametric statistics for index scores, and the receiver operating curve (ROC) for break-off. RESULTS: Patients' ISS score were similar to the results from previous research, the effect size of patient-non-patient difference was 0.68, correlations indicated a higher level of shame in depression than in anxiety, and the BDI-BAI correlation was 0.56 for both clinical samples. The PCA showed three factors that were identified as: "Inadequacy", "Emptiness", and "Vulnerability". CONCLUSIONS: The ISS is a viable instrument, which indicates a widespread shame pathology in both depressive and anxious out-patients. The instrument may not be uni-dimensional, but exploration of factor variation may be a promising goal for further research. CLINICAL IMPLICATIONS: Assessment of shame should be included in diagnosis and treatment of emotional disorder.


Assuntos
Assistência Ambulatorial , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Comparação Transcultural , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Inventário de Personalidade/estatística & dados numéricos , Vergonha , Adulto , Feminino , Humanos , Masculino , Noruega , Psicometria/estatística & dados numéricos , Valores de Referência , Autoimagem , Fatores Sexuais , Tradução , Adulto Jovem
2.
Biochem Pharmacol ; 78(12): 1438-47, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19665448

RESUMO

Insulin-like growth factor 1 receptor (IGF-1R) is an attractive target for anti-cancer therapy due to its anti-apoptotic effect on tumor cells, but inhibition of insulin receptor (IR) may have undesired metabolic consequences. The primary sequences of the ATP substrate-binding sites of these receptors are identical and the crystal structures of the activated kinase domains are correspondingly similar. Thus, most small-molecule inhibitors described to date are equally potent against the activated kinase domains of IGF-1R and IR. In contrast, the non-phosphorylated kinase domains of these receptors have several structural features that may accommodate differences in binding affinity for kinase inhibitors. We used a cell-based assay measuring IGF-1R autophosphorylation as an inhibitor screen, and identified a potent purine derivative that is selective compared to IR. Surprisingly, the compound is a weak inhibitor of the activated IGF-1R tyrosine kinase domain. Biochemical and structural studies are presented that indicate the compound preferentially binds to the ATP site of non-phosphorylated IGF-1R compared to phosphorylated IGF-1R. The potential selectivity and potency advantages of this binding mode are discussed.


Assuntos
Receptor IGF Tipo 1/antagonistas & inibidores , Receptor de Insulina/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Animais , Sítios de Ligação , Humanos , Concentração Inibidora 50 , Camundongos , Células NIH 3T3 , Fosforilação , Fosfotransferases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
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