CLEONICE DA SILVA
Índice h a partir de 2011
4
Projetos de Pesquisa
Unidades Organizacionais
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
conferenceObject Novel Mutations in MVK Associated with Hyperimmunoglobulinemia D with Periodic Fever Syndrome Phenotype(2014) VASCONCELOS, D. Moraes; FUJIHIRA, E.; OLIVEIRA, J. B.; JESUS, A. A.; SILVA, C.; CASTRO, A. P. M.; DORNA, M. B.; WATANABE, L.; PONTILLO, A.; CHUFFI-BARROS, N.; JACOB, C. M. A.; CARNEIRO-SAMPAIO, M. M. S.; DUARTE, A. J.- Hyperbaric Oxygen Therapy Induces Kidney Protection in an Ischemia/Reperfusion Model in Rats(2012) RAMALHO, R. J.; OLIVEIRA, P. S. T. de; CAVAGLIERI, R. C.; SILVA, C.; MEDEIROS, P. R. B.; MARTINI FILHO, D.; POLI-DE-FIGUEIREDO, L. F.; NORONHA, I. L.Ischemia/reperfusion (I/R) injury remains a major cause of graft dysfunction, which impacts short- and long-term follow-up. Hyperbaric oxygen therapy (HBO), through plasma oxygen transport, has been currently used as an alternative treatment for ischemic tissues. The aim of this study was to analyze the effects of HBO on kidney I/R injury model in rats, in reducing the harmful effect of I/R. The renal I/R model was obtained by occluding bilateral renal pedicles with nontraumatic vascular clamps for 45 minutes, followed by 48 hours of reperfusion. HBO therapy was delivered an hypebaric chamber (2.5 atmospheres absolute). Animals underwent two sessions of 60 minutes each at 6 hours and 20 hours after initiation of reperfusion. Male Wistar rats (n = 38) were randomized into four groups: sham, sham operated rats; Sham+HBO, sham operated rats exposed to HBO; I/R, animals submitted to I/R; and I/R+HBO, I/R rats exposed to HBO. Blood, urine, and kidney tissue were collected for biochemical, histologic, and immunohistochemical analyses. The histopathological evaluation of the ischemic injury used a grading scale of 0 to 4. HBO attenuated renal dysfunction after ischemia characterized by a significant decrease in blood urea nitrogen (BUN), serum creatinine, and proteinuria in the I/R+HBO group compared with I/R alone. In parallel, tubular function was improved resulting in significantly lower fractional excretions of sodium and potassium. Kidney sections from the I/R plus HBO group showed significantly lower acute kidney injury scores compared with the I/R group. HBO treatment significantly diminished proliferative activity in I/R (P < .05). There was no significant difference in macrophage infiltration or hemoxygenase-1 expression. In conclusion, HBO attenuated renal dysfunction in a kidney I/R injury model with a decrease in BUN, serum creatinine, proteinuria, and fractional excretion of sodium and potassium, associated with reduced histological damage.
- Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats(2022) CASTRO, Leticia Urbano Cardoso; OTSUKI, Denise Aya; SANCHES, Talita Rojas; SOUZA, Felipe Lima; SANTINHO, Mirela Aparecida Rodrigues; SILVA, Cleonice da; NORONHA, Irene de Lourdes; DUARTE-NETO, Amaro Nunes; GOMES, Samirah Abreu; MALBOUISSON, Luiz-Marcelo Sa; ANDRADE, LuciaHemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 mu g/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.
conferenceObject Hyperbaric Oxygen Therapy Induces Kidney Protection in the Ischemia/Reperfusion Model(2012) RAMALHO, R. J.; OLIVEIRA, P. S. T.; CAVAGLIERI, R. C.; SILVA, C.; MEDEIROS, P. R. B.; MARTINI-FILHO, D.; POLI-DE-FIGUEIREDO, L. F.; NORONHA, I. L.- Tamoxifen and bone morphogenic protein-7 modulate fibrosis and inflammation in the peritoneal fibrosis model developed in uremic rats(2019) SILVA, Filipe M. O.; COSTALONGA, Elerson C.; SILVA, Cleonice; CARREIRA, Ana C. O.; GOMES, Samirah A.; SOGAYAR, Mari C.; FANELLI, Camilla; NORONHA, Irene L.Background Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting peritoneal membrane (PM) integrity and function. Understanding the mechanisms underlying PF development in an uremic environment aiming alternative therapeutic strategies for treating this process is of great interest. The aim of this study was to analyze the effects of tamoxifen (TAM) and recombinant BMP7 (rBMP7) in an experimental model of PF developed in uremic rats. Methods To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and CKD with severe uremia, was developed in Wistar rats. PF was induced by intraperitoneal (IP) injections of chlorhexidine gluconate (CG), and CKD was induced by an adenine-rich diet. Uremia was confirmed by severe hypertension, increased blood urea nitrogen (BUN> 120 mg/dL) and serum creatinine levels (> 2 mg/dL). Uremic rats with PF were treated with TAM (10 mg/Kg by gavage) or BMP7 (30 mu g/Kg, IP). Animals were followed up for 30 days. Results CG administration in uremic rats induced a striking increase in PM thickness, neoangiogenesis, demonstrated by increased capillary density, and failure of ultrafiltration capacity. These morphological and functional changes were blocked by TAM or rBMP7 treatment. In parallel, TAM and rBMP7 significantly ameliorated the PM fibrotic response by reducing alpha-SMA, extracellular matrix proteins and TGF-ss expression. TAM or rBMP7 administration significantly inhibited peritoneal Smad3 expression in uremic rats with PF, prevented Smad3 phosphorylation, and induced a remarkable up-regulation of Smad7, an intracellular inhibitor of TGF beta/Smad signaling, contributing to a negative modulation of profibrotic genes. Both treatments were also effective in reducing local inflammation, possibly by upregulating I kappa B-alpha expression in the PM of uremic rats with PF. In vitro experiments using primary peritoneal fibroblasts activated by TGF-ss confirmed the capacity of TAM or rBMP7 in blocking inflammatory mediators, such as IL-1 ss expression. Conclusions In conclusion, these findings indicate important roles of TGF-ss/Smad signaling in PF aggravated by uremia, providing data regarding potential therapeutic approaches with TAM or rBMP7 to block this process.
conferenceObject Podocyte Injury in Membranous and Proliferative Lupus Nephritis: Distinct Underlying Mechanisms?(2012) REZENDE, Gabriela M.; VIANA, Vilma S. T.; MALHEIROS, Denise M.; LEON, Elaine P.; BORBA, Eduardo F.; SILVA, Neila A. S.; NORONHA, Irene L.; SILVA, Cleonice; BONFA, EloisaBackground/Purpose: Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) with proteinuria being the predominant common manifestation and may therefore reflect podocyte injury. Podocytes are highly specialized cells that have a relevant role in the glomerular filtration barrier and alteration in the expression of their biomarkers has been shown to be associated with podocyte dysfunction in some glomerulopathies. A systematic analysis of podocyte-associated molecules encom-passing different subcellular compartments was performed in a large series of LN biopsies. Expression of Wilms tumor protein (WT1), Synaptopodin (Synpo) and glomerular epithelial protein 1 (GLEPP1) with nuclear, cytoplasmic and membrane distribution respectively, were evaluated attempting to identify if podocyte phenotype is distinct in proliferative and membranous nephritis. Possible association of molecular expression alterations with long term proteinuria severity and outcome in lupus was also investigated. Methods: Immunohistochemistry analysis was performed using monoclonal antibodies to WT1, Synpo and GLEPP1 proteins in 52 biopsies from patients with lupus nephritis fulfilling the revised ACR criteria for SLE. Demographic, clinical and laboratorial data at the time of biopsy were analyzed. Results: Thirty-nine (75%) biopsies were classified as proliferative LN and thirteen (25%) as pure membranous class V. Immunohistochemistry analysis in normal kidney revealed preserved staining of WT1, Synpo and GLEPP1 podocyte biomarkers along the capillary walls. Preserved and concomitant WT1 and Synpo staining was observed in a significant higher frequency in pure class V biopsies than in proliferative LN (69.23 vs. 2.56%, p 0.0001). Likewise, preserved GLEPP1 expression was also more frequent in pure class V LN (53.85 vs. 2.86%, p 0.0002). Proteinuria and serum albumin levels at the time of biopsy did not statistically differ in the two groups (p 0.87 and p 0.41) whereas in the mean long-term follow-up of four years a tendency of lower proteinuria (p 0.050) was observed in those patients with biopsies expressing preserved WT1/Synpo staining. Conclusion: This is the first study comparing proliferative and membranous lupus nephritis which evaluated simultaneously the expression of proteins in different subcellular podocyte compartments and provided novel evidence of preserved podocyte structural architecture predominantly in membranous lesions which may account for a better long term outcome of patients with this LN histological class. These findings suggest possible different underlying mechanisms for proteinuria in both conditions.- Podocyte injury in pure membranous and proliferative lupus nephritis: distinct underlying mechanisms of proteinuria?(2014) REZENDE, G. M.; VIANA, V. S.; MALHEIROS, D. M. A. C.; BORBA, E. F.; SILVA, N. A. S.; SILVA, C.; LEON, E. P.; NORONHA, I. L.; BONFA, E.Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26 +/- 0.23 vs. 0.84 +/- 0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome.
- Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice(2013) SANTANA, Alexandre C.; DEGASPARI, Sabrina; CATANOZI, Sergio; DELLE, Humberto; LIMA, Larissa De Sa; SILVA, Cleonice; BLANCO, Paula; SOLEZ, Kim; SCAVONE, Cristoforo; NORONHA, Irene L.Persistent systemic inflammation has been widely recognized in patients with chronic kidney disease (CKD), and is associated with increased risk of morbidity and mortality. Intervention therapies aiming for the blockade of inflammatory cytokines are considered attractive approaches for CKD patients with signs of chronic inflammation. In this context, thalidomide, due to its potent anti-inflammatory and immunomodulatory properties, may represent an alternative strategy of treatment. In the present study, we developed an experimental model of CKD with uraemia in mice, induced by a diet rich in adenine, which causes progressive renal dysfunction, resembling the human uraemic features. Inflammatory parameters were analysed in this model of CKD and the potential beneficial effects of thalidomide as an anti-inflammatory drug was also investigated. C57/BL-6 mice were fed with an adenine-containing diet during a period of 6 weeks. Thirty mice were divided into three groups: Control group (animals receiving normal diet), ADE group (mice receiving adenine-containing diet) and ADE TLD group (CKD mice receiving thalidomide, 30 mg/kg/day, by gavage). Besides biochemical and histopathological changes, local and systemic inflammatory parameters were also analysed, including expression of cytokines interleukin (IL)-1, tumour necrosis factor-, IL-6, IL-4 and IL-10 in kidney samples by real-time RTPCR and quantification of serum levels of cytokines. Finally, the electrophoretic mobility shift assay (EMSA) for NF-B was also examined. Adenine-fed mice developed advanced CKD characterized by a marked increase in serum urea, creatinine, phosphorus and intact parathyroid hormone (iPTH) levels. In addition, histological changes of tubulointerstitial injury, characterized by deposition of crystals in the kidney, accompanied by tubular dilatation, degeneration of proximal tubular epithelium with loss of the brush border, inflammatory cellular infiltration, foreign-body granuloma formation and interstitial fibrosis were also evident. By immunohistochemistry, Mac-2- and -SMA-positive cells were identified in the tubulointerstitial compartment. Treatment with thalidomide significantly reduced serum urea, creatinine, phosphorus and iPTH levels and protected against tubulointerstitial injury. Local and systemic inflammation in the mice model of adenine-induced CKD was confirmed by the findings of significantly high expression of cytokine mRNA levels and NF-B activation in the kidney tissue as well as marked increased serum levels of in?ammatory cytokines. Thalidomide treatment significantly reduced gene expression of these cytokines and the activation of the NF-B in the renal tissue and the circulating levels of cytokines. Dietary adenine caused advanced CKD with uraemia in mice providing a useful experimental model to study molecular and morphological changes associated with this disease. The negative impact of inflammation in this CKD model was overcome by the marked anti-inflammatory effects of thalidomide, promoting renal protection.