Drawbacks of ovarian ablation with goserelin in women with breast cancer

In the last few years, ovarian ablation with GnRH agonists has been used as first-line adjuvant therapy in pre and perimenopausal breast cancer. These drugs suppress ovarian function in the hypothalamic-pituitary axis and they have adverse effects in other end-organs. A retrospective study was conducted on 35 premenopausal women, with breast cancer, and treated with goserelin, in order to investigate the effects of iatrogenic estrogen suppression. All women complaint of amenorrhea and only half of them referred hot-flashes, weight gain or arthralgias. Hot-flushes and arthralgias remit spontaneously in the end of the treatment. Osteodensitometry was used to access bone mass. There was a reduction in mineral bone mass and T-score at femoral neck and lumbar spine after the treatment with goserelin, but without statistical significance, except for the T-score in lumbar spine

A Flow System for Generation of Concentration Perturbation in Two-Dimensional Correlation Near-Infrared Spectroscopy: Application to Variable Selection in Multivariate Calibration

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)A flow system is proposed to produce a concentration perturbation in liquid samples, aiming at the generation of two-dimensional correlation near-infrared spectra. The system presents advantages in relation to batch systems employed for the same purpose: the experiments are accomplished in a closed system; application of perturbation is rapid and easy; and the experiments can be carried out with micro-scale volumes. The perturbation system has been evaluated in the investigation and selection of relevant variables for multivariate calibration models for the determination of quality parameters of gasoline, including ethanol content, MON (motor octane number), and RON (research octane number). The main advantage of this variable selection approach is the direct association between spectral features and chemical composition, allowing easy interpretation of the regression models.645507513Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [140289/2002-0

The ups and downs of cellular stress: the “MAM hypothesis” for Bipolar Disorder pathophysiology

info:eu-repo/semantics/publishedVersio

Inflammation in Bipolar Disorder: Identification of New Therapeutic Targets

Introdução: A doença bipolar é um distúrbio mental com origem no conceito “mania”. Trata-se de uma patologia crónica, de natureza cíclica, caracterizada pelo aparecimento de episódios alternados de mania/hipomania com episódios de eutimia/depressão. Com este artigo pretendemos identificar novas abordagens terapêuticas para o tratamento da doença bipolar, tendo em consideração o envolvimento da inflamação na sua fisiopatologia. Métodos: Revisão da literatura que relaciona a doença bipolar com a inflamação e possíveis alvos terapêuticos, baseada em artigos de revisão. Pesquisa de ensaios clínicos que permitam avaliar as novas intervenções terapêuticas. Resultados: O tratamento farmacológico da doença bipolar é complexo, sendo periodicamente adaptado à fase de doença. Para a compreensão da fisiopatologia da doença bipolar são propostas várias hipóteses relacionadas com o processo inflamatório subjacente, como a ativação patológica da microglia, desvendando um vasto leque de alvos terapêuticos. Atualmente estão a decorrer alguns ensaios clínicos que avaliam a eficácia das novas estratégias terapêuticas. Conclusão: Distúrbios mentais como a doença bipolar têm suscitado preocupação na comunidade científica e médica devido ao seu impacto ao nível social e económico. Tendo em conta o envolvimento da inflamação na fisiopatologia da doença bipolar, o sistema imunitário constitui um novo alvo terapêutico. Assim, surgem novas opções de tratamento que incluem fármacos anti-inflamatórios não esteroides e antagonistas do glutamato. Estas novas abordagens requerem mais estudos, nomeadamente a realização de ensaios clínicos.info:eu-repo/semantics/publishedVersio

Evolution of Xylan Substitution Patterns in Gymnosperms and Angiosperms: Implications for Xylan Interaction with Cellulose.

The interaction between cellulose and xylan is important for the load-bearing secondary cell wall of flowering plants. Based on the precise, evenly spaced pattern of acetyl and glucuronosyl (MeGlcA) xylan substitutions in eudicots, we recently proposed that an unsubstituted face of xylan in a 2-fold helical screw can hydrogen bond to the hydrophilic surfaces of cellulose microfibrils. In gymnosperm cell walls, any role for xylan is unclear, and glucomannan is thought to be the important cellulose-binding polysaccharide. Here, we analyzed xylan from the secondary cell walls of the four gymnosperm lineages (Conifer, Gingko, Cycad, and Gnetophyta). Conifer, Gingko, and Cycad xylan lacks acetylation but is modified by arabinose and MeGlcA. Interestingly, the arabinosyl substitutions are located two xylosyl residues from MeGlcA, which is itself placed precisely on every sixth xylosyl residue. Notably, the Gnetophyta xylan is more akin to early-branching angiosperms and eudicot xylan, lacking arabinose but possessing acetylation on alternate xylosyl residues. All these precise substitution patterns are compatible with gymnosperm xylan binding to hydrophilic surfaces of cellulose. Molecular dynamics simulations support the stable binding of 2-fold screw conifer xylan to the hydrophilic face of cellulose microfibrils. Moreover, the binding of multiple xylan chains to adjacent planes of the cellulose fibril stabilizes the interaction further. Our results show that the type of xylan substitution varies, but an even pattern of xylan substitution is maintained among vascular plants. This suggests that 2-fold screw xylan binds hydrophilic faces of cellulose in eudicots, early-branching angiosperm, and gymnosperm cell walls.This work was supported by the Leverhulme Trust Centre for Natural Material Innovation (MBW, PD), The Low Carbon Energy University Alliance (AL), BBSRC Grant: BB/G016240/1 BBSRC Sustainable Bioenergy Centre cell wall sugars (TT, PD) and the Sao Paulo Research Foundation (RLS, CSP, MSS, TCFG) (Grants 2013/08293-7, 2014/10448-1 and 2015/25031-1)

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

<p>Abstract</p> <p>Background</p> <p>Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO) mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice.</p> <p>Methods</p> <p>The grade (0 to 4) of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57) mice.</p> <p>Results</p> <p>Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive) remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68) using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice.</p> <p>Conclusion</p> <p>The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.</p

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts