RESUMO
Squamous cell carcinoma (SCC) of horn is frequently observed in Bos indicus affecting 1% of cattle population and accounting 83.34% of total tumours found. The transcriptome profile of horn cancer (HC) tissue and the matched normal (HN) tissue were analysed by RNA-seq using Roche 454 sequencing. A total of 1 504 900 reads comprising of 612 MB data were used to identify differentially expressed genes using CLC Genomic Workbench. These include up-regulation of KRT6A, KRT6B, KRT6C, KRT14, SFN, KRT84, PI3, COL17A1, ANLN, SERPINB5 and down-regulation of BOLA, SCGB1A1, CXCL17, KRT19, BPIFB1, NR4A1 and TFF3 in HC, which are involved in regulation of gene transcription, cell proliferation, apoptosis, cell survival and metabolic pathways. The qPCR analysis of several targets suggested concordance of gene expression profile with RNA-seq analysis. The present findings would provide basis for further screening of genes and identification of markers for early diagnosis and therapeutic intervention of HC.
Assuntos
Carcinoma de Células Escamosas/veterinária , Doenças dos Bovinos/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Cornos/patologia , Animais , Carcinoma de Células Escamosas/metabolismo , Bovinos , Estudo de Associação Genômica Ampla , Reação em Cadeia da Polimerase/veterinária , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , TranscriptomaRESUMO
BACKGROUND: Zonisamide has been associated with weight loss in children and adults. AIMS OF THE STUDY: To assess the effects of adjunctive zonisamide on weight and body mass index (BMI) in children with partial epilepsy. METHODS: A subanalysis was conducted of a Phase III trial and extension study, in which children with partial epilepsy received adjunctive zonisamide (target dose 8 mg/kg/day; maximum 500 mg/day). Changes in weight were correlated with skeletal development and sexual maturation. RESULTS: Overall, 179 children (93 male, 86 female; age 6-18 years) received zonisamide (mean duration 370.6 days). Weight loss ≥ 5% was reported for 64 of 179 (35.8%) zonisamide-treated children. Of these, 46.9% were overweight/obese at study entry, compared with 23.4% at study end (P = 0.0007); 48.4% had normal weight at study entry, compared with 65.6% at study end (P = 0.03). Three patients were underweight at study entry, and four more became underweight by study end. No consistent correlations between weight loss and skeletal development or sexual maturation were observed. CONCLUSIONS: Approximately one-third of children treated with zonisamide experienced ≥ 5% weight loss. Weight loss was most apparent in children with high baseline BMI values and did not appear to be associated with any consistent effects on growth and development.
Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsias Parciais/tratamento farmacológico , Isoxazóis/efeitos adversos , Redução de Peso/efeitos dos fármacos , Adolescente , Índice de Massa Corporal , Criança , Feminino , Humanos , Masculino , ZonisamidaRESUMO
Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.
Assuntos
Alanina/análogos & derivados , Antiparkinsonianos/uso terapêutico , Benzilaminas/uso terapêutico , Levodopa/uso terapêutico , Atividade Motora/efeitos da radiação , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Atividades Cotidianas , Idoso , Alanina/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Índice de Gravidade de DoençaRESUMO
We report seven cases of "rotatory seizures" with patients rotating around their axis one or several times. Contralateral EEG foci were localized in frontal and temporal regions. Computed tomography scan of three patients showed no structural lesion.
Assuntos
Movimento , Convulsões/diagnóstico , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiopatologia , Criança , Eletroencefalografia , Feminino , Humanos , Masculino , Movimento/fisiologia , Postura , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Comportamento Estereotipado/fisiologia , Tomografia Computadorizada por Raios XRESUMO
The cases of identical twins with ataxia telangiectasia, early intellectual impairment and progressive spasticity are reported. Immunological tests revealed reduced levels of serum and salivary IgA, increased B cells, reduced T cells and raised alpha-fetoprotein. CT scan performed in one of the twins was normal. The pathogenesis of the spasticity is discussed.