Tamoxifen stimulates arachidonic acid release from rat liver cells by an estrogen receptor-independent, non-genomic mechanism

BACKGROUND: Tamoxifen is widely prescribed for the treatment of breast cancer. Its success has been attributed to the modulation of the estrogen receptor. I have previously proposed that the release of arachidonic acid from cells may also mediate cancer prevention. METHODS: Rat liver cells were radiolabelled with arachidonic acid. The release of [(3)H] arachidonic acid after various times of incubation of the cells with tamoxifen was measured. RESULTS: Tamoxifen, at micromolar concentrations, stimulates arachidonic acid release. The stimulation is rapid and is not affected by pre-incubation of the cells with actinomycin or the estrogen antagonist ICI-182,780. CONCLUSIONS: The stimulation of AA release by tamoxifen is not mediated by estrogen receptor occupancy and is non-genomic

The effect of regular walks on various health aspects in older people with dementia: protocol of a randomized-controlled trial

<p>Abstract</p> <p>Background</p> <p>Physical activity has proven to be beneficial for physical functioning, cognition, depression, anxiety, rest-activity rhythm, quality of life (QoL), activities of daily living (ADL) and pain in older people. The aim of this study is to investigate the effect of walking regularly on physical functioning, the progressive cognitive decline, level of depression, anxiety, rest-activity rhythm, QoL, ADL and pain in older people with dementia.</p> <p>Methods/design</p> <p>This study is a longitudinal randomized controlled, single blind study. Ambulatory older people with dementia, who are regular visitors of daily care or living in a home for the elderly or nursing home in the Netherlands, will be randomly allocated to the experimental or control condition. Participants of the experimental group make supervised walks of 30 minutes a day, 5 days a week, as part of their daily nursing care. Participants of the control group will come together three times a week for tea or other sedentary activities to control for possible positive effects of social interaction. All dependent variables will be assessed at baseline and after 6 weeks, and 3, 6, 9, 12 and 18 months of intervention.</p> <p>The dependent variables include neuropsychological tests to assess cognition, physical tests to determine physical functioning, questionnaires to assess ADL, QoL, level of depression and anxiety, actigraphy to assess rest-activity rhythm and pain scales to determine pain levels. Potential moderating variables at baseline are: socio-demographic characteristics, body mass index, subtype of dementia, apolipoprotein E (ApoE) genotype, medication use and comorbidities.</p> <p>Discussion</p> <p>This study evaluates the effect of regular walking as a treatment for older people with dementia. The strength of this study is that 1) it has a longitudinal design with multiple repeated measurements, 2) we assess many different health aspects, 3) the intervention is not performed by research staff, but by nursing staff which enables it to become a routine in usual care. Possible limitations of the study are that 1) only active minded institutions are willing to participate creating a selection bias, 2) the drop-out rate will be high in this population, 3) not all participants will be able to perform/understand all tests.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1482">NTR1482</a></p