1. Pharmacogenomics

Category Archives: Pharmacogenomics

Human Security Thesis, personalized medicine, pharmacogenomics, Pharmacogenomics – Introduction – Video

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Human Security Thesis, personalized medicine, pharmacogenomics, Pharmacogenomics - Introduction - Video

Antidepressant Use Increases Significantly – Video

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A study released by the Center for Disease Control and Prevention this week found that the use of antidepressants has jumped 400 percent in the past 20 years. The data found that 11 percent of those over the age of 12 have taken an antidepressant during the 2005-08 study period. David Mrazek, MD, psychiatrist at Mayo Clinic, said the study means a lot of Americans are on drugs for depression, which isn't necessarily good or bad

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Antidepressant Use Increases Significantly - Video

A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs

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Original Article

The Pharmacogenomics Journal advance online publication 20 July 2010; doi: 10.1038/tpj.2010.60

F Han1,4, H Yu1,4, C Tian1, H E Chen1, C Benedict-Alderfer1, Y Zheng1, Q Wang1,5, X Han1 and Q Y Zheng1,2,3

1. Department of Otolaryngology-HNS, Case Western Reserve University, Cleveland, OH, USA
2. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA
3. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA

Correspondence: Dr QY Zheng, Department of Otolaryngology-HNS, Case Western Reserve University, 11100 Euclid Avenue, LKS 5045, Cleveland, OH 44106, USA. E-mail: qing.zheng@case.edu

4These authors contributed equally to this work.

5Current address: Department of Otolaryngology and HNS, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853 China.

Received 4 November 2009; Revised 4 June 2010; Accepted 14 June 2010; Published online 20 July 2010.
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Abstract

We report a novel mutation (erlong, erl) of the cadherin 23 (Cdh23) gene in a mouse model for DFNB12 characterized by progressive hearing loss beginning from postnatal day 27 (P27). Genetic and sequencing analysis revealed a 208?T >C transition causing an amino-acid substitution (70S–P). Caspase expression was upregulated in mutant inner ears. Hearing was preserved (up to 35-dB improvement) in pan-caspase inhibitor Z-VAD-FMK-treated mutants compared with untreated mutants (P<0.05). Outer hair cell (OHC) loss in the cochleae of Z-VAD-FMK-treated mutants was significantly reduced compared with those of untreated mice. Thus, the erl mutation can lead to hearing loss through apoptosis. This is the first genetic mouse model of hearing loss shown to respond to otoprotective drug therapy. The short interval from initial hearing loss to deafness (P27–P90) makes this model ideal for screening and validating otoprotective drugs.

Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer

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FROM NATURE COMMUNICATIONS | for ARTICLE click here.

  • Daniel Herranz,

  • Maribel Muñoz-Martin,

  • Marta Cañamero,

  • Francisca Mulero,

  • Barbara Martinez-Pastor,

  • Oscar Fernandez-Capetillo

  • & Manuel Serrano

      • Abstract
    Genetic overexpression of protein deacetylase Sir2 increases longevity in a variety of lower organisms, and this has prompted interest in the effects of its closest mammalian homologue, Sirt1, on ageing and cancer. We have generated transgenic mice moderately overexpressing Sirt1 under its own regulatory elements (Sirt1-tg). Old Sirt1-tg mice present lower levels of DNA damage, decreased expression of the ageing-associated gene p16Ink4a, a better general health and fewer spontaneous carcinomas and sarcomas. These effects, however, were not sufficiently potent to affect longevity. To further extend these observations, we developed a metabolic syndrome-associated liver cancer model in which wild-type mice develop multiple carcinomas. Sirt1-tg mice show a reduced susceptibility to liver cancer and exhibit improved hepatic protection from both DNA damage and metabolic damage. Together, these results provide direct proof of the anti-ageing activity of Sirt1 in mammals and of its tumour suppression activity in ageing- and metabolic syndrome-associated cancer.


    1. Pharmacogenomics