Pharmacogenetics Reality Or Fction? Or Are We There Yet?

[No abstract available]6902:00:00151152Twardowschy, C.A., Werneck, L.C., Scola, R.H., Depaola, L., Silvado, C.E., CYP2C9 polymorphisms in patients with epilepsy. Genotypic frequency analyzes and phe-nytoin adverse reactions correlations (2011) Arq Neurop-siquiatr, 69, pp. 153-158Glauser, T., Bem-Menachen, E., Bourgeois, B., ILAE treatment guidelines: Evidence-based analysis of an-tiepileptic drug efcacy and efectiveness as initialmonotherapy for epileptic seizures and syndromes (2006) Epilepsia, 47, pp. 1094-1120Gidal, B.E., French, J.A., Grossman, P., le Teuf, G., Assessment of potential drug interactions in patients with epilepsy:Impact of age and sex (2009) Neurology, 72, pp. 419-425Vogel, F., Moderne probleme der humangenetik (1959) Ergeb Inn Med Kinder-heilkd, 12, pp. 52-125Johnson, J.A., Pharmacogenetics: Potential for individualized drug therapy through genetics (2003) Trends Genet, 19, pp. 660-666Initial sequencing and analysis of the human genome (2001) Nature, 409, pp. 860-921. , International Human Genome Sequence ConsortiumJordan, D.M., Ramensky, V.E., Sunyaev, S.R., Human allelic variation: Perspective from protein function, structure, and evolution (2010) Curr Opin Struct Biol, 20, pp. 342-350Evans, B.J., Establishing clinical utility of pharmacogenetic tests in the post-FDAAA era (2010) Clin Pharmacol Ther, 88, pp. 749-751Hamburg, M.A., Collins, F.S., The path to personalized medicine (2010) N Engl J Med, 363, pp. 301-304(2009) Carbamazepine (market As Car-batrol, Equetro, Tegretol and Generics), , http:www.fda.gov/cder/drug/InfoSheet/HCP/carba-mazepineHCP.htm, Information for healthcare professionals, FDA Alert 12/12/07, updated 1/31/0

Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.1129113

The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.UNICAMP FCM Departamento de Genética MedicaUSP Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto Departamento de BiologiaUNICAMP Centro Multidisciplinar de Investigação BiológicaUSP IFSC Departamento de Física e BioinformáticaUNIFESP-EPM Departamento de FisiologiaUNIFESP-EPM Departamento de Neurologia e NeurocirurgiaUNICAMP FCM Departamento de Clínica MédicaUNICAMP FCM Departamento de NeurologiaUNIFESP, EPM, Depto. de FisiologiaUNIFESP, EPM Depto. de Neurologia e NeurocirurgiaSciEL

Do We Need A New Look In The Definition Of X-linked Recessive Disorders? [precisamos Ter Uma Nova Visão Da Definição Das Desordens Recessivas Ligadas Ao X?]

[No abstract available]707483484Rosenberg, R.N., Translational research in neurology and neuroscience 2010-2011 (2010) Arch Neurol, 67, p. 1176Uchihara, T., Expanding morphological dimensions in neuropathology, from sequence biology to pathological sequences and clinical consequences (2011) Neuropathol, 31, pp. 201-207Berciano, J., Peripheral neuropathies: Molecular diagnosis of Charcot-Marie-Tooth disease (2011) Nat Rev Neurol, 7, pp. 305-306Tabatabai, G., Hegi, M., Stupp, R., Weller, M., Clinical implications of molecular neuropathology and biomarkers for malignant glioma (2012) Curr Neurol Neurosci Rep, 12, pp. 302-307Dobyns, W.B., Filauro, A., Tomson, B.N., Inheritance of most X-linked traits is not dominant or recessive, just X-linked (2004) Am J Med Genet, 129, pp. 136-143Benson, K.R., Morgan's resistance to the chromosome theory (2001) Nat Rev Genet, 2, pp. 469-474Morgan, T.H., Sturtevant, A.H., Muller, H.J., Bridges, C.B., (1922) The Mechanism of Mendelian Heredity, , New York: Henry Holt & CompanyLourenço, C.M., Simão, G.N., Santos, A.C., Marques, W., X-Linked adrenoleukodystrophy in heterozygous female patients: Women are not just carriers (2012) Arq Neuropsiquiatr, 70, pp. 487-491Powers, J.M., Moser, H.W., Moser, A.B., Ma, C.K., Elias, S.B., Norum, R.A., Pathologic findings in adrenoleukodystrophy heterozygotes (1987) Arch Pathol Lab Med, 111, pp. 151-153Nussbaum, R.L., McInnes, R.R., Willard, H.F., Boerkoel, C.F.R., (2007) Thompson & Thompson: Genetics In Medicine, , Philadelphia: W.B. Saunders CoLyon, M.F., Sex chromatin and gene action in the mammalian X chromosome (1962) Am J Hum Genet, 14, pp. 135-148Willard, H.F., The sex chromosomes and X chromosome inactivation (2000) The Metabolic and Molecular Bases of Inherited Diseases, pp. 1191-1221. , In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Vogelstein B, 8th edition. New York: McGraw-HillOrstavik, K.H., X chromosome inactivation in clinical practice (2009) Hum Genet, 126, pp. 363-37

Thalamic metabolic abnormalities in patients with Huntington's disease measured by magnetic resonance spectroscopy

Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.72272

Role of non-coding RNAs in non-aging-related neurological disorders

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOProtein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regula518CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãosem informação2016/22447-52011/506802013/07559-

Rqc: a bioconductor package for quality control of high-throughput sequencing data

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOAs sequencing costs drop with the constant improvements in the field, next-generation sequencing becomes one of the most used technologies in biological research. Sequencing technology allows the detailed characterization of events at the molecular level,87CN2114FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2013/24801-2sem informaçã

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most frequent autosomal dominant ataxi4912FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2007/57559-9; 2013/07559-3sem informaçã