RESUMO
BACKGROUND: Arachidonic acid metabolites are implicated in the pathogenesis of asthma although only limited information is available on the impact of current smoking history on these metabolites. The aim of the study was to examine the effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations and relevant enzyme transcripts in asthma. METHODS: In 108 smokers and never smokers with asthma and 45 healthy controls [smokers and never smokers], we measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4 , induced sputum fluid LTB4 , LTE4 , PGD2 , and PGE2 , plasma secretory phospholipase A2 (sPLA2 ), and 11ß prostaglandin F2α (11ßPGF2α ), and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA expression levels of arachidonic acid metabolic enzymes. RESULTS: Smokers with asthma had higher urinary LTE4 ; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012 concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157) vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4 (P = 0.013), and plasma 11ßPGF2α (P = 0.032), concentrations, respectively, were increased in smokers with asthma compared with healthy smokers. Asthma-specific and smoking-related increases (>1.5-fold expression) in arachidonate 15-lipoxygenase and gamma-glutamyltransferase transcripts were demonstrated. CONCLUSIONS: Several arachidonic acid metabolites and enzyme transcripts involving both lipoxygenase and cyclooxygenase pathways are increased in smokers with asthma and differ from never smokers with asthma. Possibly targeting specific lipoxygenase and cyclooxygenase pathways that are activated by asthma and cigarette smoking may optimize therapeutic responses.
Assuntos
Ácido Araquidônico/metabolismo , Asma/genética , Asma/metabolismo , Fumar , Transcrição Gênica , Adulto , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Estudos Transversais , Feminino , Expressão Gênica , Humanos , Leucócitos/metabolismo , Leucotrieno E4/sangue , Leucotrieno E4/metabolismo , Leucotrieno E4/urina , Masculino , Pessoa de Meia-Idade , Prostaglandinas/sangue , Prostaglandinas/urina , RNA Mensageiro/genética , Testes de Função Respiratória , Mucosa Respiratória/metabolismo , Fatores de Risco , Escarro/metabolismo , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The epidermal growth factor receptor-targeted monoclonal antibody cetuximab (Erbitux) was recently introduced for the treatment of metastatic colorectal cancer. Treatment response is dependent on Kirsten-Ras (K-Ras) mutation status, in which the majority of patients with tumour-specific K-Ras mutations fail to respond to treatment. Mutations in the oncogenes B-Raf and PIK3CA (phosphoinositide-3-kinase) may also influence cetuximab response, highlighting the need for a sensitive, accurate and quantitative assessment of tumour mutation burden. METHODS: Mutations in K-Ras, B-Raf and PIK3CA were identified by both dideoxy and quantitative pyrosequencing-based methods in a cohort of unselected colorectal tumours (n=102), and pyrosequencing-based mutation calls correlated with various clinico-pathological parameters. RESULTS: The use of quantitative pyrosequencing-based methods allowed us to report a 13.7% increase in mutation burden, and to identify low-frequency (<30% mutation burden) mutations not routinely detected by dideoxy sequencing. K-Ras and B-Raf mutations were mutually exclusive and independently associated with a more advanced tumour phenotype. CONCLUSION: Pyrosequencing-based methods facilitate the identification of low-frequency tumour mutations and allow more accurate assessment of tumour mutation burden. Quantitative assessment of mutation burden may permit a more detailed evaluation of the role of specific tumour mutations in the pathogenesis and progression of colorectal cancer and may improve future patient selection for targeted drug therapies.
Assuntos
Carcinoma/genética , Neoplasias Colorretais/genética , Análise Mutacional de DNA/métodos , Individualidade , Mutação , Oncogenes/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma/cirurgia , Estudos de Coortes , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/fisiologia , Análise de Sequência de DNA/métodosRESUMO
Transmissible spongiform encephalopathies (TSE) are a group of invariably fatal neurodegenerative diseases and include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease in deer and elk, and Kuru disease, Creutzfeldt-Jakob disease (CJD) and variant CJD in humans. The pathological effects of disease occur predominantly in the CNS (central nervous system), where common hallmarks include vacuolation, gliosis, accumulation of a protease-resistant, abnormally folded isoform of the prion protein (PrPSc) and neuronal cell death. Lack of understanding of the molecular mechanisms underlying disease pathogenesis, particularly in non-CNS tissues, means that there are currently no effective strategies for early diagnosis or therapeutic intervention of TSEs. Here we report the first identification of a molecular marker that is easily detectable in readily accessible tissues. We demonstrate that a dramatic decrease in expression of a transcript specific to erythroid lineage cells is a common feature of TSEs. Our findings indicate a previously unrecognized role for involvement of the erythroid lineage in the etiology of TSE pathogenesis and should provide a new focus for research into diagnostic and therapeutic strategies.
Assuntos
Biomarcadores , Doenças Priônicas/diagnóstico , Ativinas , Animais , Linhagem Celular , Humanos , Inibinas/genética , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Doenças Priônicas/genética , Doenças Priônicas/metabolismo , Príons/genética , Príons/metabolismoRESUMO
OBJECTIVE: To show an original technique of a new combined vaginal-laparoscopic lateral suspension in Hysteropexy with cistocele and rectocele. In recent years, changes in attitudes toward sexuality, psychological value of reproductive organs and the desire to preserve fertility have led to a growing interest in uterine-preserving surgery for Pelvic Organ prolapse. Minimally invasive procedures derived from sacrocolpopexy are considered the gold standard in the treatment of apical Pelvic Organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese women and when an anatomical variation exists. This may be associated with rare but serious neurological or ureteral morbidity as well as life-threatening vascular injury. MATERIALS AND METHODS: Stepwise demonstration of the technique with narrated video footage. Local institutional review board was consulted, and this study was exempted from approval. RESULTS: Our technique entails 2 times. During the vaginal time, a polypropylene mesh is fixed to the cervical fascia and the 2 extremities are introduced in the abdominal cavity through the Douglas pouch. During the laparoscopic time, a retroperitoneal tunnel is made along the walls of the lateral abdominal walls; thereafter, each of the 2 extremities of the mesh is passed through the omolateral tunnel and "tension-free" suspended to the abdominal wall. CONCLUSION: Our combined technique may allow a safer approach, reducing the risks of serious complications. Moreover, it leads to a more physiological orientation of the vaginal axis. Further controlled studies are needed to confirm our suggestion.
Assuntos
Prolapso de Órgão Pélvico/cirurgia , Vagina/cirurgia , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Implantação de Prótese/métodos , Telas Cirúrgicas , Procedimentos Cirúrgicos Urogenitais/métodosRESUMO
OBJECTIVES: Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20 antigen exposed on B cells surface. Kinetic of B-cells repopulation after depletion therapy shows high intra and inter-individual variability. The aim of this study was to explore the influence of Body Mass Index (BMI) on kinetic of B-cell repopulation after treatment with OCR and on treatment response. METHODS: 108 Multiple Sclerosis (MS) patients were enrolled at the time of the first dose of OCR administration and prospectively evaluated. Clinical, instrumental activity and disability progression were analyzed. According to B cells count, patients were divided into two groups: with fast (FR) and with slow (SR) repopulation rate, respectively. RESULTS: Significant reduction of disease activity was observed in all patients and a stabilization of disease was obtained in progressive patients. Patients with FR had higher BMI compared to patients with a SR (p<0.001). Contrariwise no correlation between repopulation rate and treatment effectiveness was disclosed. CONCLUSIONS: In a real world setting we confirmed the effectiveness of OCR in relapsing remitting and progressive patients; patients with higher BMI had a FR. This suggests considering BMI for administration schedule although further investigations with longer follow up could improve treatment protocol and patient selection.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Anticorpos Monoclonais Humanizados , Antígenos CD20 , Índice de Massa Corporal , Humanos , Fatores Imunológicos/uso terapêutico , Cinética , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
In this work a new clustering approach is used to explore a well- known dataset [Whitfield, M. L., Sherlock, G., Saldanha, A. J., Murray, J. I., Ball, C. A., Alexander, K. E., et al. (2002). Molecular biology of the cell: Vol. 13. Identification of genes periodically expressed in the human cell cycle and their expression in tumors (pp. 1977-2000)] of time dependent gene expression profiles in human cell cycle. The approach followed by us is realized with a multi-step procedure: after preprocessing, parameters are chosen by using data sub sampling and stability measures; for any used model, several different clustering solutions are obtained by random initialization and are selected basing on a similarity measure and a figure of merit; finally the selected solutions are tuned by evaluating a reliability measure. Three different models for clustering, K-means, Self-organizing Maps and Probabilistic Principal Surfaces are compared. Comparative analysis is carried out by considering: similarity between best solutions obtained through the three methods, absolute distortion value and validation through the use of Gene Ontology (GO) annotations. The GO annotations are used to give significance to the obtained clusters and to compare the results with those obtained in the work cited above.
Assuntos
Análise por Conglomerados , Perfilação da Expressão Gênica , Genoma , Estatística como Assunto , Algoritmos , Inteligência Artificial , Ciclo Celular/genética , Humanos , Reconhecimento Automatizado de PadrãoRESUMO
The Z and W sex chromosomes of birds have evolved independently from the mammalian X and Y chromosomes [1]. Unlike mammals, female birds are heterogametic (ZW), while males are homogametic (ZZ). Therefore male birds, like female mammals, carry a double dose of sex-linked genes relative to the other sex. Other animals with nonhomologous sex chromosomes possess "dosage compensation" systems to equalize the expression of sex-linked genes. Dosage compensation occurs in animals as diverse as mammals, insects, and nematodes, although the mechanisms involved differ profoundly [2]. In birds, however, it is widely accepted that dosage compensation does not occur [3-5], and the differential expression of Z-linked genes has been suggested to underlie the avian sex-determination mechanism [6]. Here we show equivalent expression of at least six of nine Z chromosome genes in male and female chick embryos by using real-time quantitative PCR [7]. Only the Z-linked ScII gene, whose ortholog in Caenorhabditis elegans plays a crucial role in dosage compensation [8], escapes compensation by this assay. Our results imply that the majority of Z-linked genes in the chicken are dosage compensated.
Assuntos
Proteínas Aviárias , Aves/genética , Mecanismo Genético de Compensação de Dose , Cromossomos Sexuais , Aconitato Hidratase/genética , Actinas/genética , Animais , Proteínas de Ciclo Celular , Embrião de Galinha , Proteínas de Ligação a DNA/genética , Feminino , Folistatina , Glicoproteínas/genética , Hormônio do Crescimento/genética , Masculino , Proteínas Nucleares/genética , Fatores de Transcrição/genéticaRESUMO
We previously reported reduced expression of erythroid-associated factor (ERAF) within haematopoietic tissues of rodent scrapie models, suggesting an unrecognized role for the erythroid lineage in prion disease. In the present study, we compared the expression of a panel of erythroid genes within four murine scrapie models and five virus infection models with parallels to prion disease pathogenesis. We report that differential expression of erythroid genes is not limited to ERAF, and is a common feature of murine scrapie, dependent on host expression of cellular prion protein. In contrast, erythroid gene expression was not altered following virus infection. Whilst these results further implicate cells of the erythroid lineage in the peripheral pathogenesis of prion disease, analysis of blood from BSE-infected cattle and scrapie-infected sheep reveals that the extent of differential expression of erythroid genes within peripheral blood is not sufficient to provide a discriminatory diagnostic test.
Assuntos
Células Eritroides/metabolismo , Perfilação da Expressão Gênica , Doenças Priônicas/metabolismo , Infecções por Alphavirus/metabolismo , Animais , Biomarcadores/metabolismo , Infecções por Cardiovirus/metabolismo , Bovinos , Modelos Animais de Doenças , Encefalopatia Espongiforme Bovina/metabolismo , Feminino , Gammaherpesvirinae , Infecções por Herpesviridae/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Scrapie/metabolismo , Vírus da Floresta de Semliki , Ovinos , TheilovirusAssuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Encefalite/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Síndromes Paraneoplásicas/diagnóstico , Diagnóstico Diferencial , Encefalite/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Proteínas Priônicas/genética , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Mutação , Transtornos da Visão/etiologiaRESUMO
Searching for novel genes involved in tissue remodeling during ovarian folliculogenesis, we carried out differential display RT-PCR (DDRT-PCR) on RNA from gonadotropin-stimulated rat granulosa cells (GC). GC from preantral and early antral follicles in immature rat ovaries were cultured in serum-free medium containing no hormone (control), recombinant human FSH (10 ng/ml), 5alpha-dihydrotestosterone (DHT; 10(-6) M), or FSH plus DHT. Total cellular RNA was extracted from cells at 6, 12, 24, and 48 h of treatment for DDRT-PCR analysis, corresponding to an estimated 60% saturation of the messenger RNA (mRNA) population. Six distinct complementary DNA clones were obtained that reproduced the DDRT-PCR profile on a Northern blot of the corresponding RNA samples. Two of these clones detected transcripts that were strongly down-regulated by FSH. One corresponded to connective tissue growth factor (CTGF), a cysteine-rich secreted protein related to platelet-derived growth factor that is implicated in mitogenesis and angiogenesis, and a second was identical to lysyl oxidase (LO), a key participant in extracellular matrix deposition. In detailed expression studies, Northern analysis revealed a single, approximately 2.5-kb CTGF transcript maximally suppressed within 3 h of exposure to FSH with or without DHT and two LO transcripts ( approximately 3.8 and approximately 5.2 kb) maximally suppressed at 6 h. DHT alone did not affect CTGF mRNA, but strongly enhanced LO mRNA relative to the control value. In vivo, CTGF and LO transcripts were significantly suppressed in GC 48 h after equine CG injection (10 IU, ip) compared with untreated controls and were further reduced 12 h after administration of additional 10 IU hCG to induce luteinization. In situ hybridization confirmed GC in preantral/early antral follicles as principal sites of CTGF and LO mRNA expression. We conclude that expression of CTGF and LO mRNAs is inversely related to GC differentiation. The encoded proteins probably have roles in the regulation of tissue remodeling and extracellular matrix formation during early follicular development.
Assuntos
Células da Granulosa/metabolismo , Substâncias de Crescimento/genética , Proteínas Imediatamente Precoces/genética , Peptídeos e Proteínas de Sinalização Intercelular , Proteína-Lisina 6-Oxidase/genética , RNA Mensageiro/metabolismo , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Gonadotropina Coriônica/farmacologia , Fator de Crescimento do Tecido Conjuntivo , Di-Hidrotestosterona/farmacologia , Regulação para Baixo , Feminino , Hormônio Foliculoestimulante/farmacologia , Gonadotropinas Equinas/farmacologia , Folículo Ovariano/fisiologia , RNA Mensageiro/antagonistas & inibidores , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: The purpose of this study was to investigate the reliability of a new semistructured diagnostic interview, the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), for substance-abusing patients. The reliability of psychiatric diagnoses for individuals who drink heavily or use drugs has been shown to be problematic. The PRISM was designed to improve the reliability for such individuals. METHOD: A test-retest reliability study of the PRISM was conducted with 172 patients being treated in dual-diagnosis or substance abuse settings. RESULTS: Good to excellent reliability was shown for many diagnoses, including affective disorders, substance use disorders, eating disorders, some anxiety disorders, and psychotic symptoms. The interview has recently been updated for DSM-IV diagnoses. CONCLUSIONS: The PRISM offers a method of producing psychiatric diagnoses with improved reliability for patients and other research subjects who have problems with alcohol or drugs.
Assuntos
Transtornos Mentais/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/epidemiologia , Diagnóstico Duplo (Psiquiatria) , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Psicometria , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Terminologia como AssuntoRESUMO
Differential display (DD) is a powerful molecular tool that allows the identification and subsequent isolation of transcripts differentially expressed between biological samples, for example, between undifferentiated and differentiated cells, between different tissues or in one tissue at different stages of development. However, significantly high rates of apparent false positives have been reported using this technique. We suggest that the vast majority of false positives do not represent the originally selected transcript, but instead result from the re-amplification of cDNA species that co-migrate with the cDNA of interest in DD gels. Here we describe the use of a procedure to resolve co-migrating cDNAs and to purify the candidate of interest before cloning. The use of this modified technique resolves downstream problems encountered during DD experiments.
Assuntos
DNA Complementar/análise , Genes/genética , Animais , Artefatos , Northern Blotting , Encéfalo/metabolismo , Química Encefálica , Clonagem Molecular , DNA Complementar/genética , Reações Falso-Positivas , Amplificação de Genes , Expressão Gênica/genética , Camundongos , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , RNA/análise , RNA/genéticaRESUMO
The authors trace the history of the classification of anxiety disorders, beginning with a detailed discussion of Freud's work on anxiety-neurosis as a basis for subsequent work. They discuss how anxiety disorders were described in DSM-I and DSM-II where Freud's concept of the anxiety neurosis was used as a major organizing principle. The revolutionary change in DSM-III is described in which the term and organizing principle of neurosis was dropped. The controversies that have arisen as a result of changes in DSM-III-R are discussed, particularly as they relate to compatibility with the International Classification of Diseases-10 (ICD-10) and especially with respect to the relationship and priority of panic and agoraphobia. Finally the authors discuss the process by which decisions will be made in DSM-IV where changes will be based on systematic reviews of empirical evidence whenever possible.
Assuntos
Transtornos de Ansiedade/história , Transtorno de Pânico/história , Escalas de Graduação Psiquiátrica/história , Transtornos de Ansiedade/classificação , Europa (Continente) , Teoria Freudiana/história , História do Século XIX , História do Século XX , Humanos , Transtorno de Pânico/classificação , Estados UnidosRESUMO
The work on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) poses many puzzling conundrums that touch on complicated and important theoretical and practical issues. None of these can be resolved in the DSM-IV, but we hope that the Task Force's decisions will be informed by thorough reviews of the currently available evidence and extensive input from all sectors of the mental health field. In this article we provide an alphabetical guide to DSM-IV conundrums that we hope will stimulate comments, suggestions, and criticisms about the work of the Task Force.
Assuntos
Transtornos Mentais/classificação , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Diagnóstico Diferencial , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Transtornos da Personalidade/classificação , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/psicologia , PsicometriaRESUMO
No existing diagnostic interview assesses severity of dependence based on DSM-IV criteria across a range of substances. The Substance Dependence Severity Scale (SDSS) was designed to serve this purpose, consisting of substance-specific scales of both severity and frequency of DSM-IV criteria. This study investigated the reliability and validity of the SDSS. The test-retest reliability of the SDSS in 175 (112 male and 63 female) treated substance users ranged from good to excellent for alcohol, cocaine, heroin and sedatives (interclass correlation coefficients (ICCs)=0.75-0.88 for severity, 0.67-0.85 for frequency). Results for cannabis were lower, ranging from fair to good (ICCs=0.50-0.62). Results for joint rating and internal consistency reliability were comparable to test-retest findings. In addition to indicators of concurrent validity, scale applications are presented and discussed.
Assuntos
Alcoolismo/diagnóstico , Entrevista Psicológica , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adolescente , Adulto , Idoso , Alcoolismo/classificação , Alcoolismo/reabilitação , Transtornos Relacionados ao Uso de Cocaína/classificação , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Feminino , Dependência de Heroína/classificação , Dependência de Heroína/diagnóstico , Dependência de Heroína/reabilitação , Humanos , Masculino , Abuso de Maconha/classificação , Abuso de Maconha/diagnóstico , Abuso de Maconha/reabilitação , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Psicometria , Reprodutibilidade dos Testes , Transtornos Relacionados ao Uso de Substâncias/classificação , Transtornos Relacionados ao Uso de Substâncias/reabilitaçãoRESUMO
This study investigated the concurrent and predictive validity of the Substance Dependence Severity Scale (SDSS), a clinician-administered interview designed to assess the severity and frequency of DSM-IV dependence symptoms for a range of substances. A total of 172 (107 males and 66 females) treated substance users participated in the study. Of those, 89% (n=153) received at least one follow-up interview within 1-6 months of an initial assessment. For alcohol, cocaine and heroin, convergent and discriminant validity was supported by significant relationships between SDSS scores at baseline and other baseline measures of substance use consequences, such as the Addiction Severity Index (ASI), as well as significant relationships between SDSS change scores from baseline to follow-up and change scores of other measures of consequences. SDSS scores were significantly associated with time to first post treatment use of alcohol, cocaine and heroin, although the nature of the associations was complex. Scale applications and areas for further study are discussed.
Assuntos
Alcoolismo/diagnóstico , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Dependência de Heroína/diagnóstico , Entrevista Psicológica , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Alcoolismo/classificação , Alcoolismo/reabilitação , Transtornos Relacionados ao Uso de Cocaína/classificação , Transtornos Relacionados ao Uso de Cocaína/reabilitação , Seguimentos , Dependência de Heroína/classificação , Dependência de Heroína/reabilitação , Humanos , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Psicometria , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
While it is well established that cellular prion protein (PrP(C)) expression is required for the development of transmissible spongiform encephalopathies (TSEs), the physiological function of PrP(C) has yet to be determined. A number of studies have examined PrP expression in different tissues and in the later stages of embryonic development. However, the relative levels of expression of PrP RNA and protein in tissues outside the central nervous system (CNS) is not well documented and the exact point of transcriptional activation of PrP during embryogenesis is unknown. We have studied PrP mRNA expression in murine embryos and both mRNA and protein expression in a variety of adult tissues. PrP RNA was detected at different levels in all tissues tested while PrP(C) protein was detectable in all adult tissues tested with the exception of kidney and liver. RNA and protein levels were also assessed at four points during postnatal brain development and levels of both were seen to increase with development. We also established that, during embryogenesis, induction of PrP RNA expression occurs between E8.5 and E9, during the period of transition from anaerobic to aerobic metabolism. Preliminary experiments investigating the effects of superoxide radicals on PrP expression in cultured neuroblastoma and astrocyte cells support the suggestion that PrP(C) forms part of a cellular antioxidant defense mechanism.
Assuntos
Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas PrPC/metabolismo , Doenças Priônicas/genética , Ativação Transcricional/genética , Vísceras/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Animais Recém-Nascidos , Antioxidantes/metabolismo , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Embrião de Mamíferos/embriologia , Metabolismo Energético/genética , Feto , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Proteínas PrPC/efeitos dos fármacos , Proteínas PrPC/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Superóxidos/farmacologia , Ativação Transcricional/efeitos dos fármacos , Vísceras/embriologiaRESUMO
The Substance Dependence Severity Scale (SDSS) is a semistructured interview that assesses the severity of the DSM-IV diagnoses of dependence and abuse and the ICD-10 diagnoses of substance dependence and harmful use across a wide range of substances. Previous research has demonstrated that the SDSS' DSM-IV dependence scales are reliable and valid indicators of diagnostic severity. However, the ICD-10 scales have not been psychometrically tested. This study investigated the test-retest reliability, internal consistency, diagnostic concordance, and concurrent validity of the SDSS' ICD-10 dependence and harmful use scales in 180 (112 male and 68 female) treated substance users. Test-retest reliabilities for the ICD-10 dependence scales ranged from good to excellent for alcohol, cocaine, heroin, and cannabis. Test-retest reliabilities for the SDSS' ICD-10 harmful use scales were in the good range for alcohol, cocaine, and heroin and the poor to fair range for cannabis. Internal consistency, diagnostic concordance, and concurrent validity results were comparable to the test-retest findings. These results support the use of the SDSS for assessing the severity of the ICD-10 dependence and harmful use diagnoses.
Assuntos
Escalas de Graduação Psiquiátrica , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Feminino , Humanos , Entrevista Psicológica , Masculino , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Ultrasonographic and radionuclide imaging of kidney in presence of major vesicoureteric reflux, diagnosed in the first months of life, reflects a congenital anomaly of development of ureteric bud and metanephric blastema, more than a parenchymal damage secondary to superimposed infections. These lesions are mainly observed in male infants affected by reflux and referred on the basis of a prenatal diagnosis. The impact of therapy on these kidneys is still debated. PATIENTS AND METHODS: Among 273 pediatric patients with VUR observed between 1991 and 2000, 48 cases have been selected where a reflux grade III or greater had been diagnosed within the first six months of life. Cause of admission was prenatal diagnosis in 29 cases and recurrent infection in 19. Reflux was bilateral in 30 patients. Cases of VUR associated to other urological or neurological anomalies were excluded. A complete ultrasonographic, cystographic and radionuclide study was performed in all patients included in the present study within the fourth month of life. Mean Follow up lasted 17 months. Renal damage was graded by ultrasonography and DMSA renal scan on the basis or of a reduction in total kidney size and a poor radionuclide uptake either of an altered renal profile associated to focal defects of uptake. RESULTS: Resolution of reflux within the mean follow up period, was observed in 16 patients, even with high grade VUR, whenever major renal lesions were absent or focal. When severe renal damage was initially demonstrated the expectancy of reduction or resolution of VUR was significantly reduced and surgical option was considered. CONCLUSIONS: Among patients with major VUR diagnosed in the first months of life, early renal status affects prognosis more than the severity of reflux.