1,642 research outputs found

    Fulvestrant: an oestrogen receptor antagonist with a novel mechanism of action

    Get PDF
    Due to their favourable tolerability profiles, endocrine therapies have long been considered the treatment of choice for hormone-sensitive metastatic breast cancer. However, the oestrogen agonist effects of the available selective oestrogen receptor modulators, such as tamoxifen, and the development of cross-resistance between endocrine therapies with similar modes of action have led to the need for new treatments that act through different mechanisms. Fulvestrant (‘Faslodex’) is the first of a new type of endocrine treatment – an oestrogen receptor (ER) antagonist that downregulates the ER and has no agonist effects. This article provides an overview of the current understanding of ER signalling and illustrates the unique mode of action of fulvestrant. Preclinical and clinical study data are presented in support of the novel mechanism of action of this new type of ER antagonist

    Risk of dengue occurrence based on the capture of gravid Aedes aegypti females using MosquiTRAP

    Full text link
    We assessed the risk classification of dengue fever based on the capture of Aedes aegypti adults using MosquiTRAP, a type of sticky trap, in comparison with traditional larval infestation indices. A total of 27 MosquiTRAPs were installed, with one trap per block, and were inspected weekly between November 2008-February 2009. Infestation baseline data were obtained from a survey conducted prior to trap installation. The index generated by MosquiTRAP and house index (HI) classified the area "in alert situation". The set for risk of dengue occurrence proposed by the use of MosquiTRAP classify areas in the same way of the traditional HI

    Influence of ischemic core muscle fibers on surface depolarization potentials in superfused cardiac tissue preparations: a simulation study

    Get PDF
    Thin-walled cardiac tissue samples superfused with oxygenated solutions are widely used in experimental studies. However, due to decreased oxygen supply and insufficient wash out of waste products in the inner layers of such preparations, electrophysiological functions could be compromised. Although the cascade of events triggered by cutting off perfusion is well known, it remains unclear as to which degree electrophysiological function in viable surface layers is affected by pathological processes occurring in adjacent tissue. Using a 3D numerical bidomain model, we aim to quantify the impact of superfusion-induced heterogeneities occurring in the depth of the tissue on impulse propagation in superficial layers. Simulations demonstrated that both the pattern of activation as well as the distribution of extracellular potentials close to the surface remain essentially unchanged. This was true also for the electrophysiological properties of cells in the surface layer, where most relevant depolarization parameters varied by less than 5.5 %. The main observed effect on the surface was related to action potential duration that shortened noticeably by 53 % as hypoxia deteriorated. Despite the known limitations of such experimental methods, we conclude that superfusion is adequate for studying impulse propagation and depolarization whereas repolarization studies should consider the influence of pathological processes taking place at the core of tissue sample

    Oral and pharyngeal cancer in South Asians and non-South Asians in relation to socioeconomic deprivation in South East England.

    Get PDF
    From UK Thames Cancer Registry data, after controlling for socioeconomic deprivation of area of residence, South Asian males showed a higher relative risk of oral (1.36; 95% CI: 1.11, 1.67), but not of pharyngeal cancer than non-South Asian males, whereas South Asian females had much higher risks of these cancers (3.67; 95% CI: 2.97, 4.53 and 2.06; 95% CI: 1.44, 2.93), respectively, than non-South Asians
    corecore