PAULINA SANNOMIYA
Projetos de Pesquisa
Unidades Organizacionais
BMF, ICB - Docente
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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- Intrathecal injection of human umbilical cord blood stem cells attenuates spinal cord ischaemic compromise in rats(2014) JUDAS, Gustavo Ieno; FERREIRA, Sueli Gomes; SIMAS, Rafael; SANNOMIYA, Paulina; BENICIO, Anderson; SILVA, Luiz Fernando Ferraz da; MOREIRA, Luiz Felipe PinhoOBECTIVES: Spinal cord ischaemia with resulting paraplegia remains a devastating and unpredictable complication after thoraco-abdominal aortic surgery. With the advent of stem cell therapy and its potential to induce nervous tissue regeneration processes, the interest in the use of these cells as a treatment for neurological disorders has increased. Human stem cells, derived from the umbilical cord, are one of the strong candidates used in cell therapy for spinal cord injury because of weak immunogenicity and ready availability. We sought to evaluate the use of human umbilical cord blood stem cells (HUCBSCs) to attenuate the neurological effects of spinal cord ischaemia induced by high thoracic aorta occlusion. METHODS: Forty Wistar rats were randomized to receive intrathecal injection of 10 mu l phosphate buffered saline (PBS) solution containing 1 x 10(4) HUCBSCs, 30 min before (Tpre group: n = 10) and 30 min after (Tpos group: n = 10) descending thoracic aorta occlusion by intraluminal balloon during 12 min. Control groups received only PBS solution (Cpre group: n = 10; and Cpos group: n = 10). During a 28-day observational period, motor function was assessed by a functional grading scale (Basso, Beattie and Bresnahan). Segments of thoracolumbar spinal cord specimens were analysed for histological and immunohistochemical assessment for detection and quantification of human haematopoietic cells (CD45(+)) and apoptosis (transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling). RESULTS: Overall mortality was 12 animals (30%). Therefore, the observational sample was composed of 28 animals. All groups showed similar incidence of paraplegia and mortality. The mean motor function scores showed no difference during time between the animals of each group, excepting for the Tpos group, which improved from 8.14 (+/- 8.6) to 14.28 (+/- 9.8) (P < 0.01). A treatment-by-time interaction was detected among animals that received HUCBSCs 30 min after ischaemia, with BBB scores higher from Days 14 to 28 compared with the first observational day with statistical difference (P = 0.01). Number of viable neurons was higher in the Tpos group (P = 0.14) and the incidence of apoptosis was lower in the same animals (P = 0.048), but showed no difference with its respective control. We confirmed the presence of CD45(+) cells 4 weeks after intrathecal injection in both therapeutic groups but mainly in the Tpos group. CONCLUSIONS: Intrathecal transplantation of HUCBSCs is feasible, and it improved spinal cord function, when they were delivered 30 min after spinal cord ischaemia, in a model of endovascular descending thoracic aorta occlusion in rats. Human umbilical cord blood is one of the potentially useful sources of stem cells for therapy of spinal cord ischaemia.
- Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric microcirculation during early sepsis treatment(2015) GUARDA, Ismael Francisco Mota Siqueira; CORREIA, Cristiano Jesus; BREITHAUPT-FALOPPA, Ana Cristina; FERREIRA, Sueli Gomes; MORENO, Ana Carolina Ramos; MARTINEZ, Marina Baquerizo; ROCHA-E-SILVA, Mauricio; SANNOMIYA, PaulinaOBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate is endowed with antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of ethyl pyruvate on leukocyteendothelial interactions in the mesenteric microcirculation in a live Escherichia coli-induced sepsis model in rats. METHODS: Male Wistar rats were administered an intravenous suspension of E. coli bacteria or were subjected to a sham procedure. Three hours after bacterial infusion, the rats were randomized into the following groups: a control group without treatment, a group treated with lactated Ringer's solution (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg, i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte-endothelial interactions were investigated using intravital microscopy, and the expression of P-selectin and intercellular adhesion molecule-1 was evaluated via immunohistochemistry. White blood cell and platelet counts were also determined at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated and lactated Ringer's solution-treated groups exhibited increases in the numbers of rolling leukocytes (similar to 2.5-fold increase), adherent cells (similar to 3.0-fold), and migrated cells (similar to 3.5-fold) compared with the sham group. In contrast, treatment with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent and migrated leukocytes to the levels observed in the sham group. Additionally, the expression of P-selectin and intercellular adhesion molecule-1 was significantly increased on mesenteric microvessels in the non-treated group compared with the sham group (p<0.001). The expression of both adhesion molecules was reduced in the other groups, with ethyl pyruvate being more effective than lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3 h), followed by leukocytosis with granulocytosis (24 h). There was also an intense and progressive reduction in the number of platelets. However, no differences were observed after treatment with the different solutions. CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces the inflammatory response in the mesenteric microcirculation in an experimental model of sepsis induced by live E. coli and is associated, at least in part, with down-regulation of P-selectin and intercellular adhesion molecule-1.
conferenceObject EFFECTS OF 17BETA-ESTRADIOL ON A SUDDEN ONSET BRAIN DEATH MODEL IN MALE RATS(2017) VIEIRA, Roberta Figueiredo; BREITHAUPT-FALOPPA, Ana Cristina; MATSUBARA, Bruno Carvalho; RODRIGUES, Geovana; SANCHES, Marcelo Petrof; FERREIRA, Sueli Gomes; CORREIA, Cristiano De Jesus; MOREIRA, Luiz Felipe; SANNOMIYA, PaulinaconferenceObject Brain death impairs microcirculation with or without autonomic storm: an intravital microscopy study with thoracic epidural anesthesia in rats(2013) SILVA, Isaac Azevedo; SIMAS, Rafael; MENEGAT, Laura; CORREIA, Cristiano de Jesus; FERREIRA, Sueli Gomes; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe Pinho- Sex differences on solid organ histological characteristics after brain death(2016) SIMAO, Raif Restivo; FERREIRA, Sueli Gomes; KUDO, Guilherme Konishi; ARMSTRONG JUNIOR, Roberto; SILVA, Luiz Fernando Ferraz da; SANNOMIYA, Paulina; BREITHAUPT-FALOPPA, Ana Cristina; MOREIRA, Luiz Felipe PinhoPURPOSE: To investigate gender differences in the evolution of the inflammatory process in rats subjected to brain death (BD). METHODS: Adult Wistar rats were divided into three groups: female; ovariectomized female; and male rats. BD was induced using intracranial balloon inflation and confirmed by maximal pupil dilatation, apnea, absence of reflex, and drop of mean arterial pressure. Six hours after BD, histological evaluation was performed in lungs, heart, liver and kidneys, and levels of inflammatory proteins, estrogen, progesterone, and corticosterone were determined in plasma. RESULTS: In the lungs, females presented more leukocyte infiltration compared to males (p<0.01). Ovariectomized female rat lungs were more hemorrhagic compared to other groups (p<0.001). In the heart, females had higher leukocyte infiltration and tissue edema compared to males (p<0.05). In the liver and kidneys, there were no differences among groups. In female group estradiol and progesterone were sharply reduced 6 hours after BD (p<0.001) to values observed in ovariectomized females and males. Corticosterone levels were similar. CONCLUSIONS: Sex hormones influence the development of inflammation and the status of organs. The increased inflammation in lungs and heart of female rats might be associated with the acute reduction in female hormones triggered by BD.
- Acute administration of oestradiol or progesterone in a spinal cord ischaemia-reperfusion model in rats(2018) CAVALCANTE, Leonardo Pessoa; FERREIRA, Sueli Gomes; PEREIRA, Daniel Romano; MORAES, Sergio Rodrigues de; SIMAS, Rafael; SANNOMIYA, Paulina; BREITHAUPT-FALOPPA, Ana Cristina; MOREIRA, Luiz Felipe PinhoOBJECTIVES: Despite research into protective pharmacological adjuncts, paraplegia persists as a dreaded complication after thoracic and thoracoabdominal aortic interventions. Reports on gender-related neurological outcomes after ischaemic and traumatic brain injuries have led to increased interest in hormonal neuroprotective effects and have generated other studies seeking to prove the neuroprotective effects of the therapeutic administration of 17 beta-oestradiol and of progesterone. We hypothesised that acute administration of oestradiol or progesterone would prevent or attenuate spinal cord ischaemic injury induced by occlusion of the descending thoracic aorta. METHODS: Male rats were divided into groups receiving 280 A mu g/kg of 17 beta-oestradiol or 4 mg/kg of progesterone or vehicle 30 min before transitory endovascular occlusion of the proximal descending thoracic aorta for 12 min. Hindlimb motor function was assessed by a functional grading scale (that of Basso, Beattie and Bresnahan) for 14 days after reperfusion. On the 14th day, a segment of the thoracolumbar spinal cord was harvested and prepared for histological and immunohistochemical analyses. RESULTS: There was significant impairment of the motor function of the hindlimb in the 3 study groups, with partial improvement noticed over time, but no difference was detected between the groups. On Day 1 of assessment, the 17 beta-oestradiol group had a functional score of 9.8 (0.0-16.5); the progesterone group, a score of 0.0 (0-17.1) and the control group, a score of 6.5 (0-16.9); on the 14th day, the 17 beta-oestradiol group had a functional score of 18.0 (4.4-19.4); the progesterone group had a score of 7.5 (0-18.5) and the control group had a score of 17.0 (0-19.9). Analysis of the grey matter showed that the number of viable neurons per section was not different between the study groups on the 14th day. Immunostaining of the spinal cord grey matter was also similar among the 3 groups. CONCLUSIONS: Acute administration of oestradiol or of progesterone 30 min before transitory occlusion of the proximal descending thoracic aorta of male rats could not prevent or attenuate spinal cord ischaemic injury based on an analysis of functional and histological outcomes.
conferenceObject 17 beta-ESTRADIOL AS A NEW THERAPY TO PRESERVE MICROCIRCULATORY PERFUSION IN SMALL BOWEL DONOR(2019) VIEIRA, Roberta; BREITHAUPT-FALOPPA, Ana Cristina; MATSUBARA, Bruno Carvalho; FERREIRA, Sueli Gomes; DEJESUSCORREIA, Cristiano; MOREIRA, Luiz Felipe; SANNOMIYA, Paulina- 17 beta-Estradiol protects against lung injuries after brain death in male rats(2018) VIEIRA, Roberta Figueiredo; BREITHAUPT-FALOPPA, Ana Cristina; MATSUBARA, Bruno Carvalho; RODRIGUES, Geovana; SANCHES, Marcelo Petrof; ARMSTRONG- JR., Roberto; FERREIRA, Sueli Gomes; CORREIA, Cristiano de Jesus; MOREIRA, Luiz Felipe P.; SANNOMIYA, PaulinaBACKGROUND: Brain death elicits microvascular dysfunction and inflammation, and thereby compromises lung viability for transplantation. As 17 beta-estradiol was shown to be anti-inflammatory and vascular protective, we investigated its effects on lung injury after brain death in male rats. METHODS: Wistar rats were assigned to: sham-operation by trepanation only (SH, n = 7); brain death (BD, n = 7); administration of 17-estradiol (280 tg/kg, iv) at 60 minutes after brain death (BD-E2, n = 7). Experiments were performed 180 minutes thereafter. Histopathological changes in the lung were evaluated by histomorphometry. Gene expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and endothelin-1 was measured by real-time polymerise chain reaction. Protein expression of NO synthases, endothelin-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), BCL-2, and caspase 3 was assessed by immunohistochemistry. Cytokines were quantified by enzyme linked immunosorbent assay. RESULTS: Treatment with 17P-estradiol after brain death decreased lung edema and hemorrhage (p < 0.0001), and serum levels of cytokine-induced neutrophil chemoattractant-1 (CINC-1; p = 0.0020). iNOS (p < 0.0001) and VCAM-1 (p < 0.0001) also diminished at protein levels, while eNOS accumulated (p = 0.0002). However, gene expression of iNOS, eNOS, and endothelin-1 was comparable among groups, as was protein expression of endothelin-1, ICAM-1, BCL-2, and caspase 3. CONCLUSIONS: 17P-Estradiol effectively reduces lung injury in brain-dead rats mainly due to its ability to regulate NO synthases. Thus, the drug may improve lung viability for transplantation. J Heart Lung Transplant 2018;37:1381-1387 (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.
- 17 beta-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors(2020) VIEIRA, Roberta Figueiredo; BREITHAUPT-FALOPPA, Ana Cristina; CORREIA, Cristiano Jesus; ARMSTRONG JR., Roberto; COUTINHO-E-SILVA, Raphael dos Santos; FERREIRA, Sueli Gomes; MOREIRA, Luiz Felipe Pinho; SANNOMIYA, PaulinaBackground. Intestine graft viability compromises retrieval in most brain-dead donors. Small bowel transplantation is a complex procedure with worse outcomes than transplantation of other abdominal organs. The hormone 17 beta-estradiol (E2) has shown vascular protective effects in lung tissue of brain death (BD) male rats. Thus, estradiol might be a treatment option to improve the quality of intestinal grafts. Methods. Male Wistar rats were divided into 3 groups (n = 10/group): rats that were trepanned only (sham-operated), rats subjected to rapid-onset BD, and brain-dead rats treated with E2 (280 mu g/kg, intravenous) (BD-E2). Experiments performed for 180 minutes thereafter are included: (a) laser-Doppler flowmetry and intravital microscopy to evaluate mesenteric perfusion; (b) histopathological analysis; (c) real-time polymerase chain reaction of endothelial nitric oxide synthase (eNOS) and endothelin-1; (d) immunohistochemistry of eNOS, endothelin-1, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 expression; and (e) ELISA for cytokines and chemokines measurement. Results. 17 beta-Estradiol improved microcirculatory perfusion and reduced intestinal edema and hemorrhage after BD. The proportions of perfused small vessels were (mean +/- scanning electron microscope) BD rats (40% +/- 6%), sham-operated rats (75% +/- 8%), and BD-E2 rats (67% +/- 5%) (P= 0.011). 17 beta-Estradiol treatment was associated with 2-fold increase in eNOS protein (P< 0.0001) and gene (P= 0.0009) expression, with no differences in endothelin-1 expression. BD-E2 rats exhibited a reduction in vascular cell adhesion molecule 1 expression and reduced cytokine-induced neutrophil chemoattractant 1 and interleukina-10 serum levels. Conclusions. 17 beta-Estradiol was effective in improving mesenteric perfusion and reducing intestinal edema and hemorrhage associated with BD. The suggestion is that E2 might be considered a therapy to mitigate, at least in part, the deleterious effects of BD in small bowel donors.
conferenceObject ESTRADIOL TREATMENT REDUCES LUNG INFLAMMATION INDUCED BY BRAIN DEATH IN FEMALE RATS(2017) SILVA, Fernanda Yamamoto Ricardo Da; AMSTRONG JR., Roberto; SANTOS, Marina Vidal Dos; FERREIRA, Sueli Gomes; SANNOMIYA, Paulina; MOREIRA, Luiz Felipe; BREITHAUPT-FALOPPA, Ana Cristina