Angiotensin II - AT1 receptor signalling regulates the plasminogen-plasmin system in human stromal endometrial cells increasing extracellular matrix degradation, cell migration and inducing a proinflammatory profile.

The pivotal role of human endometrial stromal cells (hESCs) in the development of endometriosis lies in their ability to adopt a pro-invasive and proinflammatory profile upon migration to areas outside the uterus. However, the molecular mechanisms involved in these events remain unclear. In this study, we investigated how angiotensin II (Ang II) affects the plasminogen-plasmin system in hESCs, and the mechanisms underlying cell proliferation, migration, matrix degradation, and inflammation. Precursors, receptors, and peptidases involved in angiotensin metabolism increased significantly in Ang II-treated hESCs. The expression and activity of tissue (tPA)- and urokinase (uPA)- type plasminogen activators and the receptor for uPA (uPAR) were induced in the presence of Ang II. The up-regulation of tPA-uPA/uPAR pathway significantly contributes to heightened plasmin production both on the surface of hESCs and in their conditioned media. As a result, the plasmin generation induced by Ang II enhances the degradation of fibrin and matrix proteins, while also boosting hESC viability, proliferation, and migration through the up-regulation of growth factor expression. Notably, Ang II-induced hESC migration was dependent on the generation of active plasmin on cell surface. Ang II regulates oxidative and inflammatory signalling in hESCs primarily via NADPH oxidase and through the up-regulation of proinflammatory cytokines and adhesion molecules. Interestingly, Ang II receptor (AT1R) blockage, decreased plasmin generation, tPA-uPA/uPAR expression and hESC migration. Our results suggest that Ang II/AT1R axis regulates hESC proliferation and migration through tPA-uPA/uPAR pathway activation and plasmin generation. We propose the Ang II/AT1R axis as a potential target for endometriosis treatment.

Mechanisms involved in the cytoprotective effects of Lonomia obliqua venom on human endometrial stromal cells.

The pathophysiology of recurrent pregnancy loss (RPL) involves deficiencies in the proliferation and migration capacities of endometrial stromal cells (hESCs), which impair embryo implantation and development. Since animal venoms are rich source of bioactive molecules, we aimed to characterize the cytoprotective effects of Lonomia obliqua venom on hESCs. hESCs were isolated from endometrial biopsies and the mechanisms of L. obliqua venomous secretions on cell viability, proliferation and migration were characterized. Venom components were identified by chromatography and proteomic analyses. L. obliqua venom induced hESC proliferation, viability and migration in a dose-dependent manner, both in the presence and absence of serum. By ion-exchange chromatography, one fraction enriched in cytoprotective components and devoid of hemotoxins was obtained. Venom proteome identified at least six protein classes with potential cytoprotective properties (hemolins, lipocalins, hemocyannins, antiviral proteins, antimicrobial peptides, and protease inhibitors). L. obliqua venom protected hESCs from oxidative insult. Cytoprotection was also related to nitric oxide and PKC-ERK-activation and down-regulation of cAMP-PKA-dependent pathways that control cell proliferation. L. obliqua venom-induced hESC viability, proliferation and migration occurs mainly by protecting against oxidative damage and activating ERK. Thus, L. obliqua venom components are promising pharmacological tools to understand the underlying mechanisms of hESC deficiency in RPL.

Estrogen depletion modulates aortic prothrombotic signaling in normotensive and spontaneously hypertensive female rats.

AIM: In this study, we investigated how platelets and aorta contribute to the creation and maintenance of a prothrombotic state in an experimental model of postmenopausal hypertension in ovariectomized rats. METHODS: Bilateral ovariectomy was performed in both 14-week-old female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. The animals were kept in phytoestrogen free diet. Vascular parameters, platelet, coagulation and aortic prothrombotic functions and mechanisms were assessed. RESULTS: Exacerbated platelet aggregation was observed in both SHR and WKY animals after ovariectomy. The mechanism was related to aortic COX2 downregulation and reduction in AMP, ADP, and ATP hydrolysis in serum and platelets. A procoagulant potential was observed in plasma from ovariectomized rats and this was confirmed by kallikrein and factor Xa generation in aortic rings. Aortic rings derived from ovariectomized SHR presented a greater thrombin generation capacity compared to equivalent rings from WKY animals. The mechanism involved tissue factor and PAR-1 upregulation as well as an increase in extrinsic coagulation and fibrinolysis markers in aorta and platelets. Aortic smooth muscle cells pre-treated with a plasma pool derived from estrogen-depleted animals developed a procoagulant profile with tissue factor upregulation. This procoagulant profile was dependent on inflammatory signalling, since NFκB inhibition attenuated the procoagulant activity and tissue factor expression. CONCLUSIONS: A prothrombotic phenotype was observed in both WKY and SHR ovariectomized rats being associated with platelet hyperreactivity and tissue factor upregulation in aorta and platelets. The mechanism involves proinflammatory signalling that supports greater thrombin generation in aorta and vascular smooth muscle cells.

The Correlation between Chlamydia Trachomatis and Female Infertility: A Systematic Review / A correlação entre clamídia trachomatis e infertilidade feminina: Uma revisão sistemática

Abstract The impact of Chlamydia trachomatis (CT) infection on female's fertility is not completely established yet, since the level of evidence associating these factors is still weak. Hence, the goal of the present review is to contribute to a better elucidation of this matter. The electronic database chosen was the Medline/PubMed, with the last survey on May 11, 2021. Publication date was used as a filter, with the previous 5 years having been selected. The following describers were used: chlamydia trachomatis AND infertility; chlamydia trachomatis AND tubal alteration AND infertility; chlamydia AND low pregnancy rates. From the 322 studies screened, 293 that failed to meet our eligibility criteria were excluded. Subsequently, we removed seven studies for not having the possible correlation between CT infections and female infertility as its main focus, and three for being about sexually transmitted infections (STIs) in general. Moreover, two studies designed as reviews were also excluded. Ergo, we included 17 studies in our qualitative analysis. The authors conducted research individually and analyzed carefully the studies selected. As we retrieved the information needed for our study through reading the texts, no contact was made with the authors of the studies selected. This systematic review corroborates the hypothesis that CT infection potentiates female infertility, as 76.47% of the included studies found a positive correlation between them. We conclude that there is an important association between CT infection and female infertility. Ergo, making CT screening part of the infertility investigation routine is relevant and has a reasonable justification.

Resumo O impacto da infecção por Chlamydia trachomatis (CT) na fertilidade feminina ainda não está completamente estabelecido, uma vez que o nível de evidência associando esses fatores ainda é insignificante. Assim, o objetivo desta revisão é contribuir para uma melhor elucidação deste assunto. A base de dados eletrônica escolhida foi a Medline/PubMed, com a última pesquisa em 11 de maio de 2021. Utilizou-se como filtro a data de publicação, sendo selecionados os 5 anos anteriores. Foram usados os seguintes descritores: Chlamydia trachomatis E infertility; Chlamydia trachomatis E tubal alteration E infertility; Chlamydia E low pregnancy rates. Dos 322 estudos selecionados, 293 que não atenderam aos nossos critérios de elegibilidade foram excluídos. Posteriormente, retiramos sete estudos por não terem como foco principal a possível correlação entre infecção por CT e infertilidade feminina e três por tratarem de infecções sexualmente transmissíveis (ISTs) em geral. Além disso, dois estudos concebidos como revisões também foram excluídos. Portanto, incluímos 17 estudos em nossa análise qualitativa. Os autores realizaram pesquisas individualmente e analisaram criteriosamente os estudos selecionados. Como obtivemos as informações necessárias para nosso estudo por meio da leitura dos textos, nenhum contato foi feito com os autores. Esta revisão sistemática corrobora a hipótese de que a infecção por CT potencializa a infertilidade feminina, pois 76,47% dos estudos incluídos encontraram correlação positiva entre eles. Concluímos que existe uma associação importante entre infecção por CT e infertilidade feminina. Portanto, tornar os procedimentos de triagem por CT parte da rotina de investigação de infertilidade é relevante e justificável.

The Correlation between Chlamydia Trachomatis and Female Infertility: A Systematic Review.

The impact of Chlamydia trachomatis (CT) infection on female's fertility is not completely established yet, since the level of evidence associating these factors is still weak. Hence, the goal of the present review is to contribute to a better elucidation of this matter. The electronic database chosen was the Medline/PubMed, with the last survey on May 11, 2021. Publication date was used as a filter, with the previous 5 years having been selected. The following describers were used: chlamydia trachomatis AND infertility; chlamydia trachomatis AND tubal alteration AND infertility; chlamydia AND low pregnancy rates. From the 322 studies screened, 293 that failed to meet our eligibility criteria were excluded. Subsequently, we removed seven studies for not having the possible correlation between CT infections and female infertility as its main focus, and three for being about sexually transmitted infections (STIs) in general. Moreover, two studies designed as reviews were also excluded. Ergo, we included 17 studies in our qualitative analysis. The authors conducted research individually and analyzed carefully the studies selected. As we retrieved the information needed for our study through reading the texts, no contact was made with the authors of the studies selected. This systematic review corroborates the hypothesis that CT infection potentiates female infertility, as 76.47% of the included studies found a positive correlation between them. We conclude that there is an important association between CT infection and female infertility. Ergo, making CT screening part of the infertility investigation routine is relevant and has a reasonable justification.

O impacto da infecção por Chlamydia trachomatis (CT) na fertilidade feminina ainda não está completamente estabelecido, uma vez que o nível de evidência associando esses fatores ainda é insignificante. Assim, o objetivo desta revisão é contribuir para uma melhor elucidação deste assunto. A base de dados eletrônica escolhida foi a Medline/PubMed, com a última pesquisa em 11 de maio de 2021. Utilizou-se como filtro a data de publicação, sendo selecionados os 5 anos anteriores. Foram usados os seguintes descritores: Chlamydia trachomatis E infertility; Chlamydia trachomatis E tubal alteration E infertility; Chlamydia E low pregnancy rates. Dos 322 estudos selecionados, 293 que não atenderam aos nossos critérios de elegibilidade foram excluídos. Posteriormente, retiramos sete estudos por não terem como foco principal a possível correlação entre infecção por CT e infertilidade feminina e três por tratarem de infecções sexualmente transmissíveis (ISTs) em geral. Além disso, dois estudos concebidos como revisões também foram excluídos. Portanto, incluímos 17 estudos em nossa análise qualitativa. Os autores realizaram pesquisas individualmente e analisaram criteriosamente os estudos selecionados. Como obtivemos as informações necessárias para nosso estudo por meio da leitura dos textos, nenhum contato foi feito com os autores. Esta revisão sistemática corrobora a hipótese de que a infecção por CT potencializa a infertilidade feminina, pois 76,47% dos estudos incluídos encontraram correlação positiva entre eles. Concluímos que existe uma associação importante entre infecção por CT e infertilidade feminina. Portanto, tornar os procedimentos de triagem por CT parte da rotina de investigação de infertilidade é relevante e justificável.

Do isolamento à cogestão: a gestão autônoma da medicação (GAM) com familiares / From isolation to co-management: autonomous medication management (GAM) with family members / Del aislamiento a la cogestión: gestión autónoma de la medicación (GAM) con miembros de la familia

Este artigo apresenta a experiência de pesquisa-intervenção participativa da Gestão Autônoma da Medicação (GAM) com familiares. A GAM, de origem canadense, procura discutir criticamente o uso da medicação psiquiátrica de modo a fomentar a autonomia dos usuários desses medicamentos. No Brasil, o chamado projeto GAM-BR realizou a tradução, adaptação e validação do instrumento utilizado nesta abordagem, o Guia GAM. Seguimos as indicações teórico-práticas da abordagem enativa e empregamos a metodologia da cartografia, em especial a técnica da entrevista cartográfica. Como um projeto participativo, a validação do Guia contou com usuários e trabalhadores dos serviços de saúde mental brasileiros (Caps) como copesquisadores. A realização de um grupo com familiares de usuários na etapa de validação do Guia foi uma inovação na GAM-BR que possibilitou a inclusão desse grupo fundamental para a discussão acerca do tratamento medicamentoso. Podemos destacar dois efeitos processuais desse trabalho com familiares: a promoção de deslocamentos de ponto de vista e a promoção de corresponsabilização. Tais efeitos sugerem perspectivas para a GAM e para o trabalho em saúde mental, em um horizonte de inclusão e composição entre diferentes perspectivas.(AU)

This article presents the participatory research-intervention experience of Autonomous Medication Management (GAM) with family members. The GAM, a Canadian project, seeks to critically discuss the use of psychiatric medication to foster the autonomy of users of these drugs. In Brazil, the so-called GAM-BR project translated, adapted, and validated the instrument used in this approach, the GAM Guide. We follow the theoretical-practical indications of the enactive approach and employ the cartography methodology, in particular the cartographic interview technique. As a participatory project, the validation of the Guide included users and workers of the Brazilian mental health services (CAPS) as co-researchers. The creation of a group with family members of users in the validation phase was an innovation in GAM-BR that enabled the inclusion of this fundamental group for the discussion about drug treatment. We can highlight two processual effects of this work with family members: the promotion of displacements of points of view and the promotion of co-responsibility. These effects suggest perspectives for GAM and the work in mental health, in a horizon of inclusion and composition between different perspectives.(AU)

Este artículo presenta la experiencia participativa de intervención-investigación de la Gestión Autónoma de la Medicación (GAM) con miembros de la familia. La GAM es una guía que procede de Canadá y busca discutir críticamente el uso de medicación psiquiátrica para fomentar la autonomía de sus usuarios. En Brasil, el proyecto llamado GAM-BR realizó la traducción, adaptación y validación del instrumento utilizado en este enfoque, la Guía GAM. Se siguieron las indicaciones teóricas y prácticas del enfoque enactivo, y se utilizó la metodología de la cartografía, especialmente la técnica de entrevista cartográfica. Como proyecto participativo, la validación de la Guía incluyó a usuarios y a trabajadores brasileños de los centros de atención a salud mental (CAPS) como coinvestigadores. La creación de un grupo con familiares de usuarios en la etapa de validación de la Guía fue una innovación en GAM-BR por incluir a este grupo de fundamental importancia en la discusión sobre el tratamiento farmacológico. Es posible señalar dos efectos procesales de este trabajo con miembros de la familia: la promoción de los desplazamientos de perspectivas y la promoción de la corresponsabilización. Estos efectos sugieren perspectivas para GAM y el trabajo en salud mental, en un horizonte de inclusión y composición entre diferentes perspectivas.(AU)

Urine proteomic analysis reveals alterations in heme/hemoglobin and aminopeptidase metabolism during Lonomia obliqua venom-induced acute kidney injury.

AIMS: Accidental contact with the Lonomia obliqua caterpillar is a common event in southern Brazil. Envenomed victims present consumption coagulopathy, which can evolve to acute kidney injury (AKI). In the present study, we searched for AKI biomarkers and changes in molecular pathway signatures through urine proteomic analysis. METHODOLOGY: Male Wistar rats were injected with L. obliqua venom (1.5 mg/kg, via s.c.) or 0.9 % NaCl and distributed into metabolic cages. After 24 h, urine was obtained, and the set of differentially regulated proteins was analyzed by MudPIT technology in an OrbiTRAP mass spectrometer. RESULTS: L. obliqua venom leads to an increase in urine output and water and electrolyte excretion and to an increase in the albumin to creatine ratio in urine. The proteomic analysis revealed an up-regulation of tubular injury biomarkers, such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C, in urine from envenomed rats. Several components related to the heme scavenging system were up-regulated or exclusively identified in urine from envenomed animals. There was an increase in urinary heme levels and hemoglobin subunits, hemopexin, haptoglobin, and biliverdin reductase. Similarly, kinin- and angiotensin-generating/degrading peptidases, such as kallikreins, neprilysin, plasmin, dipeptidyl peptidase IV, cathepsin D, kininogen, and neutral, basic, glutamyl, and acidic aminopeptidases, were also up-regulated in urine. CONCLUSIONS: L. obliqua envenomation induced tubular and glomerular injury, probably involving heme/hemoglobin toxicity and an imbalance in the kinin/angiotensin generating/degrading system.

Use of clomiphene citrate protocol for controlled ovarian stimulation impairs endometrial maturity.

INTRODUCTION: Despite recent advances in assisted reproduction techniques and recent knowledge regarding embryo and endometrium quality, implantation and birth rates remain low. The objective of this study was to investigate whether clomiphene citrate alters endometrial maturation in infertile patients. METHODS: In a prospective self-matched cohort study, we assessed the ovulation of women in spontaneous and stimulated cycles (with clomiphene citrate). We determined the ovulation day by ultrasound scanning. In both cycles, we took four blood samples (BS1 - at early proliferative phase, BS2 - at mid proliferative phase, BS3 - after ovulation and BS4 - at mid luteal phase) to determine the serum concentrations of FSH, LH, estradiol and progesterone. We retrieved an endometrial biopsy five days after ovulation, followed by blinded analysis and classification according to Noyes criteria, in both cycles. RESULTS: Twenty-two participants completed the study. There were significant differences in FSH BS3 (p=0.001), in LH BS3 and BS4 (p<0.001 and p=0.049, respectively), in estradiol BS2, BS3 and BS4 (p<0.001, p=0.024 and p<0.001, respectively) and in progesterone BS3 and BS4 (p=0.028 and p<0.001, respectively). Considering Noyes criteria, there was a one-day delay when comparing the stimulated cycle with the spontaneous cycle (p=0.004), and a two-day delay when comparing the stimulated cycle with the biopsy day. CONCLUSION: This study indicates that ovarian stimulation with clomiphene citrate delays the endometrial maturity, and could possibly impair the implantation process due to asynchrony.

Narrativas sobre o impacto das técnicas de reprodução assistida na experiência da gestação / Narratives about the impact of assisted reproductive technologies on the experience of pregnancy / Narrativas sobre el impacto de las técnicas de reproducción asistida en la experiencia del embarazo

Este estudo teve como objetivo investigar as narrativas de mulheres que conceberam com o auxílio das técnicas de reprodução assistida (TRA), acerca do impacto do tratamento na experiência da gestação. Foram entrevistadas 24 mulheres no terceiro trimestre de uma gestação concebida com o auxílio de diferentes TRA. Os dados foram submetidos a uma análise narrativa, destacando-se temas como a maior valorização da gravidez devido ao tratamento, o medo de perder o bebê, a possibilidade de gestação gemelar, o preconceito social em relação ao uso das TRA e a tentativa de naturalização dessa experiência. Embora tenha predominado o não reconhecimento explícito do impacto do tratamento na experiência da gestação, as participantes demonstraram-no em nuances de suas narrativas, ao relatarem seus sentimentos e expectativas. Os resultados sugerem a importância da atuação dos profissionais de saúde mental nesse contexto.

The aim of this study was to investigate the narratives of women who conceived with the help of assisted reproductive technologies (ART), and the impact of this treatment on the experience of pregnancy. Twenty-four women in the third trimester of pregnancy, all subjected to different ART, were interviewed. Data were submitted and evaluated using narrative analysis. Topics such a greater appreciation of pregnancy because of the treatment, the fear of losing the baby, the possibility of having twins, the social prejudice against ART, and the attempts to naturalize this experience were highlighted. The explicit non-recognition of the treatment’s impact stood out. However, the participants expressed this impact when reporting feelings and expectations in their narratives. The results suggest the importance of a mental health professional taking part in this process.

Este estudio pretende investigar las narrativas de mujeres que concibieron con el auxilio de las técnicas de reproducción asistida (ART) sobre el impacto del tratamiento en la experiencia del embarazo. Fueron entrevistadas 24 mujeres en el tercer trimestre de una gestación concebida con ayuda de diferentes ARTs. Los datos fueron sometidos a un análisis narrativo, destacándose temas como la mayor valoración del embarazo debido al tratamiento, el miedo a perder al bebé, la posibilidad de embarazo gemelar, el prejuicio social en relación con el uso de las ARTs y el intento de naturalización de esta experiencia. Aunque haya predominado el no reconocimiento explícito del impacto del tratamiento en la experiencia del embarazo, las participantes lo demostraron en los matices de sus narrativas, al relatar sus sentimientos y expectativas. Los resultados sugieren la importancia de la actuación de los profesionales de salud mental en ese contexto.

Ovarian tissue vitrification is more efficient than slow freezing to preserve ovarian stem cells in CF-1 mice.

OBJECTIVE: The aim of this study was to investigate the efficacy of protocols for mice ovary cryopreservation to compare the differences in Mouse Vasa Homologue expression (a germline cell marker) and ovarian viability after vitrification or slow freezing. METHODS: Female CF1 mice aged 40-45 days were randomly divided into three groups: Control, vitrification or slow freezing. Their ovaries were surgically removed, rinsed in saline solution and cryopreserved. For vitrification, we used a commercial protocol and for slow freeze, we used 1.5 M ethylene glycol (EG) as cryoprotectant. After that, the ovaries were processed for histological an immunohistochemical analysis, and counting of primordial, primary, pre-antral and antral follicles. RESULTS: No significant difference was found in the proportion of high-quality primordial, primary and pre-antral follicles after thawing/warming in the slow freezing and vitrification groups. The immunohistochemistry for MVH antibody demonstrated that the slow freeze group had a higher number of unmarked cells (p=0.012), indicating a harmful effect on the MVH expression in the ovarian tissue, where the cell structure is complex. CONCLUSION: Although both protocols indicated similar results in the histological analysis of follicular counts, the vitrification protocol was significantly better to preserve ovarian stem cells, an immature germ cell population. These cells are able to self-renew having regeneration potential, and may be effective for the treatment of ovarian failure and consequently infertility.

Kallikrein-kinin system and oxidative stress in cisplatin-induced ovarian toxicity.

Kallikrein-kinin system (KKS) is involved in vascular reactivity and inflammatory response to cytotoxic drugs. Since cisplatin is a widely used chemotherapy and its cytotoxic mechanism can trigger inflammation and oxidative damage, in this work we evaluated the role of KKS in an animal model of cisplatin-induced ovarian toxicity. Biomarkers of ovarian stem cells, activity of KKS, inflammation and oxidative damage were measured in ovarian tissue of C57BL/6 female mice treated with vehicle or cisplatin (2.5 mg/kg). Cisplatin group presented greater number of atretic follicles, and lower numbers of antral and total viable follicles. Ki67, DDX4 and OCT-4 markers were similar between groups. Cisplatin triggered plasma and ovarian tissue kallikrein generation; and increased expression of bradykinin receptors B1 and B2. Neutrophil and macrophage infiltration markers increased. Superoxide anion generation also increased, while reduced glutathione levels decreased. These results suggest that KKS is activated and contributes to ovarian injury during cisplatin treatment.

GAM, apoio e cuidado em CAPS AD / GAM, care support in álcohol and other drugs / GAM, cuidado y apoyo em álcohol y otras drogas

Discute-se um processo de capilarização da estratégia GAM - Gestão Autônoma da Medicação - em São Paulo entre 2017 e 2018, em que trabalhadores e usuários foram convidados à investigação e experimentação do dispositivo GAM na atenção especializada no campo de álcool e outras drogas. Este processo resultou na construção de práticas de apoio distribuído entre trabalhadores e usuários e de um coletivo com potencial de ampliação de possibilidades de redução de danos. Ao longo do processo, os trabalhadores realizaram oficinas de apoio e moderaram os grupos GAM com usuários. Dois analisadores do trabalho e da clínica emergiram nesse processo compartilhado: as experiências de violência nos modos de existência dos usuários e o dia-a-dia dos trabalhadores em serviço; e a expectativa de abstinência e a frustração das "recaídas" que incidem nas relações de cuidado.

A process of capillarization of the GAM strategy - Autonomous Management of Medication - is discussed. In São Paulo, between 2017 and 2018, workers and users were invited to the investigation and experimentation of the GAM proposal in the specialized attention to the suffering in the field of alcohol and other drugs. This process resulted in the construction of a device that generates support practices distributed among workers and users and of a collective with potential to increase possibilities of harm reduction. Throughout the process, workers held "support workshops" and moderated "GAM groups" with users. Two analyzer's themes emerged in this collective process: the experiences of violence that happens in the existence of the users and the day-to-day of the workers in the institution; and the expectation of abstinence and the frustration of "relapses" that affect care relationships in the service and clinic.

Se discute un proceso de capilarización de la estrategia GAM (Gestión autónoma de medicamentos) en São Paulo entre 2017 y 2018, en el que se invitó a trabajadores y usuarios a investigar y experimentar el dispositivo GAM en atención especializada en el campo del alcohol y otras drogas. Este proceso resultó en la construcción de prácticas de apoyo distribuidas entre los trabajadores y usuarios y de un colectivo con el potencial de ampliar las posibilidades de reducción de daños. A lo largo del proceso, los trabajadores realizaron talleres de apoyo y moderaron los grupos GAM con los usuarios. Dos analizadores de trabajo y clínica surgieron en este proceso compartido: las experiencias de violencia en los modos de existencia de los usuarios y la vida cotidiana de los trabajadores en servicio; y la expectativa de abstinencia y la frustración de las "recaídas" que afectan las relaciones de atención.

A gestão autônoma da medicação e o dispositivo da pesquisa-apoio / Autonomous management of medication and the support-research device / Gestión autónoma de la medicación y el dispositivo de la investigación-apoyo

Este artigo discute uma inovação da pesquisa-intervenção participativa na abordagem da Gestão Autônoma da Medicação (GAM): a criação de uma etapa que nomeamos "Pesquisaapoio". Tal etapa se inspirou nos conceitos-ferramenta de Apoio Matricial e Apoio Institucional, instrumentos no campo brasileiro da saúde coletiva voltados à democratização dos serviços, à troca de experiências e saberes entre trabalhadores e à cogestão. A Pesquisaapoio teve objetivos semelhantes no serviço de saúde mental onde se realizou, um Centro de Atenção Psicossocial (CAPS); contudo, diferentemente daqueles instrumentos, ela inclui em seu dispositivo os usuários dos serviços e seus familiares, ao invés de incluir apenas os trabalhadores. A Pesquisa-apoio permite contribuir com o debate sobre apoio no campo da saúde e ampliar a discussão sobre os dispositivos GAM. Em continuidade com os princípios da GAM, a Pesquisa-apoio permitiu aprofundar a participação dos usuários nos processos cogestivos, reforçando sua parceria com os trabalhadores e expandindo sua autonomia.

This article discusses an innovation of the participative intervention-research in the Autonomous Management of Medication (GAM) approach: the creation of a phase that we call "Support-research". The Support-research was inspired by the concepts/tools of Matrix Support and Institutional Support, instruments in the Brazilian collective health field aiming at democratizing services, sharing experiences and knowledge between workers and promoting co-management. The Support-research had similar objectives in the mental health service where it took place, in a Centre for Psychosocial Attention (CAPS); however, unlike those instruments, it had included users of the service and their family members in the support device. The Support-research contributes to the debate about support in health services and to extend the discussion about GAM devices. In line with GAM principles, the Support-research allowed users to deepen their participation in co-managed processes, strengthen their partnership with workers and expand their autonomy.

Este artículo discute una innovación de la investigación-intervención participativa en el abordaje de la Gestión Autónoma de la Medicación (GAM): la creación de una fase que llamamos "Investigación-apoyo". La Investigación-apoyo se inspiró en los conceptosherramienta de Apoyo Matricial y Apoyo Institucional, instrumentos en el campo brasileño de la salud colectiva dirigidos a la democratización de los servicios, al intercambio de experiencias y saberes entre trabajadores y la cogestión. La Investigación-apoyo tuvo objetivos similares en el servicio de salud mental donde se realizó, un Centro de Atención Psicosocial (CAPS); sin embargo, se diferenció de aquellos instrumentos por incluir en su dispositivo a los usuarios de los servicios y sus familiares, en vez de incluir sólo a los trabajadores. La Investigación-apoyo permite contribuir con el debate sobre apoyo en el campo de la salud y ampliar la discusión sobre los dispositivos GAM. En continuidad con los principios de la GAM, la Investigación-apoyo permitió profundizar la participación de los usuarios en los procesos cogestivos, reforzando su asociación con los trabajadores y expandiendo su autonomía.

O apoio institucional ao Fórum da Rede de Saúde Mental de São Pedro da Aldeia como dimensão da pesquisa de Gestão Autônoma da Medicação / Institutional support for the Forum of São Pedro da Aldeia Mental Health Network as a dimension of the Gaining Autonomy & Medication Management research

Resumo Este artigo compartilha uma experiência de apoio institucional a um coletivo de trabalhadores de um município da Região dos Lagos, Rio de Janeiro, no período de 2011-2014. Essa experiência é efeito da pesquisa-intervenção que implantou e validou o dispositivo de Gestão Autônoma da Medicação no Centro de Atenção Psicossocial Casarão da Saúde, no município de São Pedro da Aldeia. A pesquisa estimulou a criação de um fórum de trabalhadores da Rede de Atenção Psicossocial (Raps) que funciona como espaço permanente para negociações e cuidado coletivo da experiência do cuidar na Raps. Interessa-nos, neste texto, apresentar e discutir o processo de apoio institucional à criação desse fórum como etapa importante da pesquisa realizada. A partir dessa experiência será discutida a relação entre processo de pesquisa e apoio institucional, além de suas consequentes modulações metodológicas, bem como efeitos desse processo de pesquisa-apoio para a Raps do município, que tem como prerrogativa a instalação de um dispositivo que seja capaz de cuidar da experiência de cuidar, no campo da saúde mental.

Abstract This article shares an experience of institutional support for a group of workers of a municipality of Região dos Lagos, Rio de Janeiro, Brazil, in the period 2011-2014. This experience is the result of the intervention research that implemented and validated the Gaining Autonomy & Medication Management device at the Casarão da Saúde Psychosocial Care Center, in the municipality of São Pedro da Aldeia. The research stimulated the creation of a forum of workers of the Psychosocial Care Network (Raps) which works as a permanent space for negotiations and collective care of the experience of caring in the Raps. We are interested in this text to present and discuss the process of institutional support for the creation of this forum as an important stage of the research. From this experience, the relationship between research process and institutional support will be discussed, as well as its consequent methodological modulations, and the effects of this research-support process for the municipality's Raps, which has the prerogative of installing a device capable of taking care of the experience of caring in the field of mental health.

Tissue-engineered solution containing cells and biomaterials-an in vitro study: A perspective as a novel therapeutic application.

Some biomaterial scaffolds can positively interfere with tissue regeneration and are being developed to successfully repair the tissue function. The possibility of using epithelial cells combined with biomaterials appears to be a new option as therapeutic application. This combination emerges as a possibility for patients with Mayer-Rokitansky-Kuster-Hauser syndrome which requires vaginal repair and can be performed with tissue-engineered solution containing cells and biomaterials. It is expected that tissue-engineered solution containing cells and biomaterials would promote tissue repair in a more efficient, modern, and safe way. This study tested the efficiency of tissue-engineered solution containing human malignant melanoma cell line (HMV-II) and different biomaterials, including Cellprene®, Membracel®, and poly lactic-co-glycolic acid/epoxidized polyisoprene. The cells adhered better on poly lactic-co-glycolic acid/epoxidized polyisoprene, and it was found that tissue-engineered solution may also contain mesenchymal stem cells cultivated on poly lactic-co-glycolic acid/epoxidized polyisoprene. Histological, immunofluorescence, and scanning electron microscopy analyses were performed. These initial in vitro results suggest that tissue-engineered solution containing cells and poly lactic-co-glycolic acid/epoxidized polyisoprene is a potential for tissue reconstruction.

Renal and vascular effects of kallikrein inhibition in a model of Lonomia obliqua venom-induced acute kidney injury.

BACKGROUND: Lonomia obliqua venom is nephrotoxic and acute kidney injury (AKI) is the main cause of death among envenomed victims. Mechanism underlying L. obliqua-induced AKI involves renal hypoperfusion, inflammation, tubular necrosis and loss of glomerular filtration and tubular reabsorption capacities. In the present study, we aimed to investigate the contribution of kallikrein to the hemodynamic instability, inflammation and consequent renal and vascular impairment. METHODOLOGY/PRINCIPAL FINDINGS: Addition of L. obliqua venom to purified prekallikrein and human plasma in vitro or to vascular smooth muscle cells (VSMC) in culture, was able to generate kallikrein in a dose-dependent manner. Injected in rats, the venom induced AKI and increased kallikrein levels in plasma and kidney. Kallikrein inhibition by aprotinin prevented glomerular injury and the decrease in glomerular filtration rate, restoring fluid and electrolyte homeostasis. The mechanism underlying these effects was associated to lowering renal inflammation, with decrease in pro-inflammatory cytokines and matrix metalloproteinase expression, reduced tubular degeneration, and protection against oxidative stress. Supporting the key role of kallikrein, we demonstrated that aprotinin inhibited effects directly associated with vascular injury, such as the generation of intracellular reactive oxygen species (ROS) and migration of VSMC induced by L. obliqua venom or by diluted plasma obtained from envenomed rats. In addition, kallikrein inhibition also ameliorated venom-induced blood incoagulability and decreased kidney tissue factor expression. CONCLUSIONS/SIGNIFICANCE: These data indicated that kallikrein and consequently kinin release have a key role in kidney injury and vascular remodeling. Thus, blocking kallikrein may be a therapeutic alternative to control the progression of venom-induced AKI and vascular disturbances.