ROBERTO ARMSTRONG JUNIOR

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    FEMALE RATS PRESENT HIGHER LUNG INFLAMMATION AFTER BRAIN DEATH FOLLOWED BY EX VIVO PERFUSION
    (2021) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG- JR., Roberto; OTTENS, Petra; ZANDEN, Judith van; VIDAL-DOS-SANTOS, Marina; MOREIRA, Luiz Felipe Pinho; ERASMUS, Michiel; LEUVENINK, Henri; BREITHAUPT-FALOPPA, Ana Cristina
  • article 3 Citação(ões) na Scopus
    Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats
    (2021) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG-JR, Roberto; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano de Jesus; SILVA, Raphael dos Santos Coutinho e; ANUNCIACAO, Lucas Ferreira da; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri Gerrit Derk; BREITHAUPT-FALOPPA, Ana Cristina
    OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17 beta-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17 beta-estradiol (50 mu g/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17 beta-estradiol (50 mu g/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-alpha, IL-1 beta, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-alpha and IL-1 beta gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.
  • conferenceObject
    Estradiol Modulation of Brain Death Effects on Heart Tissue in Female Rats
    (2018) ARMSTRONG JUNIOR, R.; RICARDO-DA-SILVA, F. Y.; BASILIO, L. J. L.; VIDAL, M. S.; SANNOMIYA, P.; MOREIRA, L. F. P.; BREITHAUPT-FALOPPA, A. C.
  • article 10 Citação(ões) na Scopus
    Sex-related differences in lung inflammation after brain death
    (2016) BREITHAUPT-FALOPPA, Ana Cristina; FERREIRA, Sueli G.; KUDO, Guilherme K.; ARMSTRONG JR., Roberto; TAVARES-DE-LIMA, Wothan; SILVA, Luiz Fernando Ferraz da; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe P.
    Background: Donor sex has been suggested to be a factor influencing organ transplantation outcome. Sex hormones possess inflammatory and immune-mediating properties; therefore, immune responses may differ between males and females. Brain death (BD) affects organ function by numerous mechanisms including alterations in hemodynamics, hormonal changes, and increased systemic inflammation. In this study, we investigated sex-dependent differences in the evolution of lung inflammation in a rat model of BD. Materials and methods: BD was induced by a sudden increase in intracranial pressure by rapidly inflating a balloon catheter inserted into the intracranial space. Groups of male, female, and ovariectomized (OVx) female rats were used. Lung vascular permeability, inducible nitric oxide synthase, and intercellular adhesion molecule 1 expression were analyzed 6 h after BD. Serum female sex hormones, vascular endothelial growth factor, and cytokine-induced neutrophil chemoattractant 1 levels were also quantified. Lung sections were analyzed by histology. Results: After 6 h of BD, serum estradiol and progesterone concentrations in female rats were significantly reduced. Lung microvascular permeability was increased in females compared to males. Cytokine-induced neutrophil chemoattractant 1 and vascular endothelial growth factor concentrations were increased in female rats compared to males. Furthermore, female rats showed higher levels of leukocyte infiltration and inducible nitric oxide synthase expression in the lung parenchyma. Conclusions: Our results indicate that the more severe lung inflammation in female animals after BD might be related to acute estradiol reduction. Based on our findings, we believe that, in a future study, a group of female treated with estradiol after BD could indicate a possible therapy for the control of lung inflammation in the female donor.
  • conferenceObject
    Positive Therapeutic Effect of Estradiol on Lung Inflammation in Brain Dead Female Rats
    (2018) SILVA, F. Yamamoto Ricardo da; ARMSTRONG JUNIOR, R.; VIDAL-DOS-SANTOS, M.; SANNOMIYA, P.; MOREIRA, L. F. P.; BREITHAUPT-FALOPPA, A. C.
  • article 0 Citação(ões) na Scopus
    Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
    (2024) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG-JR, Roberto; RAMOS, Mayara Munhoz de Assis; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano Jesus; OTTENS, Petra J.; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri G. D.; BREITHAUPT-FALOPPA, Ana Cristina
    BackgroundEx vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.MethodsMale and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1 beta levels. Leukocyte infiltration, myeloperoxidase presence, IL-1 beta gene expression, and long-term release in lung culture (explant) were evaluated.ResultsBrain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1 beta levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.ConclusionIn this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality. Ex vivo lung perfusion maintains lung function in lung grafts from brain dead rats, independently of sex;Inflammation is greater in female's lung grafts even after ex vivo perfusion when compared to males. As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.
  • article
    Protective role of 17 beta-estradiol treatment in renal injury on female rats submitted to brain death
    (2021) ARMSTRONG-JR, Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano de Jesus; ANUNCIACAO, Lucas Ferreira; SILVA, Raphael dos Santos Coutinho e; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri Gerrit Derk; BREITHAUPT-FALOPPA, Ana Cristina
    Background: Clinical and experimental data highlight the consequences of brain death on the quality of organs and demonstrate the importance of donor state to the results of transplantation. Female rats show higher cardio-pulmonary injury linked to decreased concentrations of female sex hormones after brain-dead (BD). This study evaluated the effect of 17 beta-estradiol on brain death induced renal injury in female rats. Methods: Female Wistar rats were randomically allocated into 4 groups: false-operation (Sham), BD, treatment with 17 beta-estradiol (50 mu g/mL, 2 mL/h) 3 h after brain death (E2-T3), or immediately after brain death confirmation (E2-T0). Creatinine, urea, cytokines, and complement system components were quantified. Renal injury markers, such as KIM-1, Caspase-3, BCL-2 and MMP2/9 were evaluated. Results: Brain death leads to increased kidney KIM-1 expression and longer 17 beta-estradiol treatment resulted in downregulation (P<0.0001). There was increase of neutrophil numbers in kidney from BD rats and E2 treatment was able to reduce it (P=0.018). Regarding complement elements, E2-T3 group evidenced E2 therapeutic effects, reducing C5b-9 (P=0.0004), C3aR (P=0.054) and C5aR (P=0.019). In parallel, there were 17 beta-estradiol effects in reducing MMP2 (P=0.0043), MMP9 (P=0.011), and IL-6 (P=0.024). Moreover, E2-T3 group improved renal function in comparison to BD group (P=0.0938). Conclusions: 17 beta-estradiol treatment was able to reduce acute kidney damage in BD female rats owing to its ability to prevent tissue damage, formation of C5b-9, and local synthesis of inflammatory mediators.
  • conferenceObject
    ESTRADIOL TREATMENT MODULATES ESTRADIOL RECEPTORS EXPRESSION AND REDUCES RENAL INJURY AFTER BRAIN DEATH IN FEMALE RATS
    (2021) CORREIA, Cristiano; ARMSTRONG- JR., Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; VIDAL-DOS-SANTOS, Marina; ANUNCIACAO, Lucas Ferreira Da; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri; BREITHAUPT-FALOPPA, Ana Cristina
  • conferenceObject
    SEX DIFFERENCES ON DONOR LEUKOCYTE MOBILIZATION AND ORGAN INFLAMMATION AFTER BRAIN DEATH
    (2015) BREITHAUPT-FALOPPA, Ana Cristina; GOMES, Ferreira Sueli; KONISHI, Kudo Guilherme; RESTIVO, Simao Raif; ARMSTRONG JR., Roberto; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe
  • article 4 Citação(ões) na Scopus
    The influence of female sex hormones on lung inflammation after brain death - an experimental study
    (2020) ABIB, Ana Luisa de Oliveira Bonnano; CORREIA, Cristiano de Jesus; ARMSTRONG- JR., Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; FERREIRA, Sueli Gomes; VIDAL-DOS-SANTOS, Marina; MOREIRA, Luiz Felipe Pinho; RIFFO-VASQUEZ, Yanira; BREITHAUPT-FALOPPA, Ana Cristina
    Organ donor's age negatively influences graft survival of organs, increasing risk of complications. Aging occurs in both men and women; however, the menopause marks a decrease in sex hormones and a sudden increase in the process of vascular aging. We investigated sex hormones' influence on the lung inflammatory process induced by BD in female rats. Wistar rats were grouped as: female rats from high estradiol to heat period (non-OVx) and ovariectomized (OVx) female rats. Ovariectomy was carried out 10 days before BD. BD was induced using intracranial balloon rapid inflation. Serum hormones and inflammatory mediators were quantified, leukocytes and platelets counted and lung samples were collected for RT-PCR, immunohistochemical, and histological analysis. Female sex hormones and corticosterone were reduced 6 h after BD in non-OVx group. The infiltration of leukocytes in female non-OVx lungs was higher compared to OVx. G-CSF, VEGF, and CINC-1 were found increased in non-OVx group serum in comparison to OVx. Lung mediators were increased in non-OVx rats compared to controls. The acute reduction of sex hormones induced by BD appears to have a worse effect on lung inflammation than a reduction that has happened over a prolonged period of time, allowing a physiological adaptation prior to BD.