Women in body and soul : biopsychosocial factors in menopause

Este trabalho investigou na literatura científica os aspectos biológicos, psicológicos e socioculturais que se estão em jogo na etapa da meia-idade feminina a fim de melhor compreender a vivência dessa mulher. O evento da menopausa caracterizada pela cessação da ovulação e por manifestações físicas e psíquicas - marca este momento vital e impõe questões que, se não forem bem trabalhadas, podem, no limite, ocasionar sintomas depressivos. As mudanças hormonais condicionam o processo de envelhecimento que aponta para a finitude. Um certo estranhamento em relação a si mesma faz com que muitas mulheres tenham dificuldades em lidar com as perdas inerentes a esta fase de vida.This study investigated biological, psychological and sociocultural aspects that interact in middle-aged women in order to better understand their feelings and experiences. The advent of the menopause- characterized by the end of the menstruation and by psychic and physical manifestations- imposes fundamental questions that, on the limit, may elicit depressive symptoms. Hormonal changes are implicated in the aging process, that point to the finitude. A feeling of not being themselves makes many women experience difficulties with losses inherent to this life period

A VIDA OUVIDA: A ESCUTA PSICOLÓGICA E A SAÚDE DA MULHER DE MEIA-IDADE

Foi realizada uma pesquisa empírica com o objetivo de avaliar a importância da escuta psicológica para a saúde da mulher de meia-idade. O mal-estar geral experimentado neste momento de vida representa o visível, que esconde questões invisíveis da história de vida pessoal. Os procedimentos qualitativos foram: 1) levantamento dos serviços de atendimento à mulher de meia-idade na rede pública hospitalar do Distrito Federal; 2) entrevistas com profissionais da área de saúde; e 3) uma intervenção psicológica grupal em um espaço público hospitalar, com mulheres de classe socioeconômica desfavorecida. O compartilhamento das experiências pessoais, a partir de temas sugeridos pelas participantes, resultou numa experiência enriquecedora e contribuiu para que a vivência da meia-idade fosse mais bem elaborada. Os profissionais da saúde indicaram o atendimento interdisciplinar para esta faixa etária. Este estudo sugere que as políticas públicas de saúde devam incluir espaços de escuta psicológica com vistas à saúde integral da mulher

The Unified National Health System and public policies : psychological care for menopausal women in the Federal District, Brazil

Objetivou-se investigar a situação de atendimento psicológico à mulher de meia-idade, na rede pública de saúde do Distrito Federal, Brasil. Discutiu-se a saúde da mulher, mais especificamente, daquela que se encontra no período da menopausa e seu lugar nas atuais políticas públicas. Levantamento realizado na rede pública apontou a existência de poucas intervenções psicológicas destinadas à mulher nesta fase do ciclo vital. Em geral, apenas o atendimento ambulatorial ginecológico era oferecido. Em nenhuma das unidades de saúde pesquisadas existiam psicólogos no quadro de pessoal, cujo trabalho fosse dedicado especificamente à mulher na meia-idade. Concluiu-se que esta etapa da vida feminina não tem sido contemplada com assistência psicológica, negligenciando os princípios fundamentais do SUS. O estudo reafirma a necessidade de essa mulher ter acesso ao atendimento integral de sua saúde, incluindo uma escuta psicológica dos conflitos relacionados às dimensões biológicas, psíquicas e sócio-culturais do processo de envelhecimento. Esta escuta especializada pode contribuir para a elaboração da maturidade feminina.This study focused on psychological care for middle-aged women in public health services in the Federal District (Brasilia), Brazil. The article discusses women’s health and more specifically menopause and its place in Brazilian public health policies. The survey confirmed the lack of psychological support for menopausal women. In most cases only outpatient medical care was offered. No psychologist had been designated in any of the units surveyed to assist these women. The study concludes that this period of women’s life has failed to receive psychological care in Brazil, thus neglecting the principles of the Unified National Health System. Menopausal women deserve comprehensive health care, including attention to conflicts related to biological, psychological, and socio-cultural dimensions of aging, thus contributing to the process of working through maturity

Mulheres de corpo e alma: aspectos biopsicossociais da meia-idade feminina

Este trabalho investigou na literatura científica os aspectos biológicos, psicológicos e socioculturais que se estão em jogo na etapa da meia-idade feminina a fim de melhor compreender a vivência dessa mulher. O evento da menopausa - caracterizada pela cessação da ovulação e por manifestações físicas e psíquicas - marca este momento vital e impõe questões que, se não forem bem trabalhadas, podem, no limite, ocasionar sintomas depressivos. As mudanças hormonais condicionam o processo de envelhecimento que aponta para a finitude. Um certo estranhamento em relação a si mesma faz com que muitas mulheres tenham dificuldades em lidar com as perdas inerentes a esta fase de vida.This study investigated biological, psychological and sociocultural aspects that interact in middle-aged women in order to better understand their feelings and experiences. The advent of the menopause - characterized by the end of the menstruation and by psychic and physical manifestations - imposes fundamental questions that, on the limit, may elicit depressive symptoms. Hormonal changes are implicated in the aging process, that point to the finitude. A feeling of not being themselves makes many women experience difficulties with losses inherent to this life period

Enhancing anticancer activity of spiropyrazoline oxindoles by disrupting p53-MDMs PPIs

Cancer is a major public health problem worldwide with 18.1 million new cases of cancer and 9.6 million deaths worldwide in 20181. The protein p53 is involved in many biological processes that are important to maintain the normal function of the cells (e.g. apoptosis, cell arrest, and DNA repair). It is an attractive target in oncology because it can modulate several additional cellular processes that are relevant for the suppression of tumour development, such as opposing oncogenic metabolic reprogramming, activating autophagy, and restraining invasion and metastasis. In all types of human cancers, the p53 tumour suppressor function is inactivated by mutation or gene deletion or by negative regulators such as MDM2 and MDMX. In the last years, the most popular approach among medicinal chemists to activate the wild-type p53 was the inhibition of p53-MDM2 protein-protein interaction (PPI) using small molecules. However, it is currently known that the full reactivation of p53 is only achieved when the interactions of p53 with both negative regulators are inhibited. Due to the lack of dual p53-MDM2/X PPIs inhibitors in clinical trials, it is urgent to develop small molecules that inhibit p53-MDMs PPIs2. Our research team has been working on the development and optimization of spiropyrazoline oxindoles to obtain dual p53-MDM2/X PPIs inhibitors. Hence, we have already developed derivatives with good antiproliferative activities in HCT-116 p53(+/+) human colorectal carcinoma cell line, which induce apoptosis and cell cycle arrest at G0/G1 phase, upregulate p53 steady-state levels, and lead to a decrease of MDM2 levels3. In this communication, we report the structure-based computational optimization of this chemical family for the development of novel p53-MDM2/X interactions inhibitors. Our studies will shed light on the possible binding mode of spirooxindole derivatives to MDM2 and MDMX and will drive the hit-to-lead optimization strategy. Furthermore, we report our most recent optimization of the synthesis of these new spiropyrazoline oxindoles derivatives and the first preliminary biological results. Acknowledgements: This work was supported by National Funds (FCT/MEC, Fundacao para a Ciencia e Tecnologia and Ministerio da Educacao e Ciencia) through UID/DTP/04138/2019 (iMed.ULisboa), project PTDC/QUI-QOR/29664/2017, Principal Investigator grant CEECIND/01772/2017 (M. M. M. Santos) and PhD fellowships SFRH/BD/137544/2018 (E.A. Lopes) and SFRH/BD/117931/2016 (M. Espadinha). 1Ferlay, J., Colombet, M., Soerjomataram, I., Mathers, C., Parkin, D., Pineros, M., Znaor, A. and Bray, F., Int. J. Cancer, 2019, 144, 1941-1953. 2Espadinha M., Barcherini V., Lopes E. A., Santos M. M. M., Curr. Top. Med. Chem. 2018, 18, 647-660. 3a) Nunes R., Ribeiro C. J. A., Monteiro Â., Rodrigues C. M. P., Amaral J. D., Santos M. M. M., Eur. J. Med. Chem., 2017, 139, 168-179. b) Amaral J. D., Silva D., Rodrigues C. M. P., Sola S., Santos M. M. M., Front. Chem., 2019, 7, article

Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity

© 2022 Published by Elsevier Masson SAS.Malaria remains a prevalent infectious disease in developing countries. The first-line therapeutic options are based on combinations of fast-acting artemisinin derivatives and longer-acting synthetic drugs. However, the emergence of resistance to these first-line treatments represents a serious risk, and the discovery of new effective drugs is urgently required. For this reason, new antimalarial chemotypes with new mechanisms of action, and ideally with activity against multiple parasite stages, are needed. We report a new scaffold with dual-stage (blood and liver) antiplasmodial activity. Twenty-six spirooxadiazoline oxindoles were synthesized and screened against the erythrocytic stage of the human malaria parasite P. falciparum. The most active compounds were also tested against the liver-stage of the murine parasite P. berghei. Seven compounds emerged as dual-stage antimalarials, with IC50 values in the low micromolar range. Due to structural similarity with cipargamin, which is thought to inhibit blood-stage P. falciparum growth via inhibition of the Na + efflux pump PfATP4, we tested one of the most active compounds for anti-PfATP4 activity. Our results suggest that this target is not the primary target of spirooxadiazoline oxindoles and further studies are ongoing to identify the main mechanism of action of this scaffold.This work was supported by FCT (Fundação para a Ciência e a Tecnologia, I.P.) through iMed.ULisboa (UID/DTP/04138/2019), project PTDC/QUI-QOR/29664/2017, and PhD fellowship SFRH/BD/137544/2018 (E. Lopes). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). Financial support from FCT and Portugal 2020 to the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa – RNEM; LISBOA-01-0145-FEDER-402-022125) is also acknowledged.info:eu-repo/semantics/publishedVersio

Discovery of MDM2-p53 and MDM4-p53 protein-protein interactions small molecule dual inhibitors

MDM2 and MDM4 are key negative regulators of p53, an important protein involved in several cell processes (e. g. cell cycle and apoptosis). Not surprisingly, the p53 tumor suppressor function is inactivated in tumors over -expressing these two proteins. Therefore, both MDM2 and MDM4 are considered important therapeutic targets for an effective reactivation of the p53 function. Herein, we present our studies on the development of spi-ropyrazoline oxindole small molecules able to inhibit MDM2/4-p53 protein-protein interactions (PPIs). Twenty-seven potential spiropyrazoline oxindole dual inhibitors were prepared based on in silico structural optimization studies of a hit compound with MDM2 and MDM4 proteins. The antiproliferative activity of the target com-pounds was evaluated in cancer cell lines harboring wild-type p53 and overexpressing MDM2 and/or MDM4. The most active compounds in SJSA-1 cells, 2q and 3b, induce cell death via apoptosis and control cell growth by targeting the G0/G1 cell cycle checkpoint in a concentration-dependent manner. The ability of the five most active spiropyrazoline oxindoles in dissociating p53 from MDM2 and MDM4 was analyzed by an immu-noenzymatic assay. Three compounds inhibited MDM2/4-p53 PPIs with IC50 values in the nM range, while one compound inhibited more selectively the MDM2-p53 PPI over the MDM4-p53 PPI. Collectively, these results show: i) 3b may serve as a valuable lead for obtaining selective MDM2-p53 PPI inhibitors and more efficient anti-osteosarcoma agents; ii) 2a, 2q and 3f may serve as valuable leads for obtaining dual MDM2/4 inhibitors and more effective p53 activators