TALITA ROJAS CUNHA SANCHES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/08 - Laboratório de Anestesiologia, Hospital das Clínicas, Faculdade de Medicina
32 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 32
- TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY(2023) MAIA, Debora Rothstein Ramos; OTSUKI, Denise Aya; RODRIGUES, Camila Eleuterio; ZBORIL, Sabrina; SANCHES, Talita Rojas; NETO, Amaro Nunes Duarte; ANDRADE, Lucia; AULER, Jose Otavio CostaBackground: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 x 106 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-kappa B signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
- Vitamin D Deficiency Aggravates Chronic Kidney Disease Progression after Ischemic Acute Kidney Injury(2014) GONCALVES, Janaina Garcia; BRAGANCA, Ana Carolina de; CANALE, Daniele; SHIMIZU, Maria Heloisa Massola; SANCHES, Talita Rojas; MOYSES, Rosa Maria Affonso; ANDRADE, Lucia; SEGURO, Antonio Carlos; VOLPINI, Rildo AparecidoBackground: Despite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-beta 1 (TGF-beta 1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD). Methods: Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-beta, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and alpha-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area. Results: IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and alpha-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-beta 1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals. Conclusion: Through inflammatory pathways and involvement of TGF-beta 1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.
- Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury(2017) RODRIGUES, Camila Eleuterio; CAPCHA, Jose Manuel Condor; BRAGANCA, Ana Carolina de; SANCHES, Talita Rojas; GOUVEIA, Priscila Queiroz; OLIVEIRA, Patricia Aparecida Ferreira de; MALHEIROS, Denise Maria Avancini Costa; VOLPINI, Rildo Aparecido; SANTINHO, Mirela Aparecida Rodrigues; SANTANA, Barbara Amelia Aparecida; CALADO, Rodrigo do Tocantins; NORONHA, Irene de Lourdes; ANDRADE, LuciaBackground: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats. Methods: By clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 x 10(6) huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49. Results: On post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (beta-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) andmicroRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased beta-galactosidase expression and increased the expression of Klotho. Conclusions: Our data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI.
- Vitamin D deficiency aggravates ischemic acute kidney injury in rats(2015) BRAGANCA, Ana Carolina de; VOLPINI, Rildo A.; CANALE, Daniele; GONCALVES, Janaina G.; SHIMIZU, Maria Heloisa M.; SANCHES, Talita R.; SEGURO, Antonio C.; ANDRADE, LuciaVitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclindependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI.
- CHRONIC NICOTINE EXPOSURE DOWNREGULATES RENAL KLOTHO EXPRESSION AND TRIGGERS DIFFERENT RENAL AND AUTONOMIC RESPONSES ACCORDING TO THE KLOTHO STATUS IN MICE(2015) COELHO, Fernanda O.; JORGE, Lecticia B.; BRAGANCA, Ana Carolina de; SANCHES, Talita R. C.; CANALE, Daniele; HELOU, Claudia M. B.; IRIGOYEN, Maria Claudia; KUROO, Makoto; ANDRADE, Lucia
- 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.
- Apolipoprotein A-I mimetic peptide 4F attenuates kidney injury, heart injury, and endothelial dysfunction in sepsis(2014) MOREIRA, Roberto S.; IRIGOYEN, Maria; SANCHES, Talita R.; VOLPINI, Rildo A.; CAMARA, Niels O. S.; MALHEIROS, Denise M.; SHIMIZU, Maria H. M.; SEGURO, Antonio C.; ANDRADE, LuciaKidney injury, heart injury, and cytokine-induced vascular hyperpermeability are associated with high rates of morbidity and mortality in sepsis. Although the mechanism remains unknown, apolipoprotein A-I (apoA-I) mimetic peptide 4F reduces inflammation and protects HDL levels, which are reduced in sepsis. We hypothesized that 4F also protects kidneys and hearts in a rat model of cecal ligation and puncture (CLP). We divided Wistar rats into groups: sham-operated (control), CLP, and CLP+4F (10 mg/kg body wt ip, 6 h after CLP). At 24 h post-CLP, we evaluated cardiac function, mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity, total cholesterol, LDL, HDL, serum cytokines, and inulin clearance. We performed immunoblotting for protein regulators of vascular permeability (Slit2 and Robo4) and endothelial nitric oxide synthase (eNOS) in kidney tissue. We evaluated heart mitochondria with electron microscopy. Although there was no difference in MAP, the HR was significantly higher in CLP rats than in control and CLP+4F rats. In CLP+4F rats, baroreflex sensitivity and cardiac function were completely protected from the effects of CLP, as was glomerular filtration; heart mitochondria morphology was improved; sepsis-induced changes in serum cholesterol, LDL, HDL, and apoA-I were less common; all cytokines were lower than in CLP rats; and expression of Slit2, Robo4, and eNOS was completely restored. Administration of 4F inhibits inflammatory responses and strengthens the vascular barrier, protecting kidneys and hearts in an HDL-dependent manner. To determine the extent of the protective effect of 4F, further studies are needed.
- Renal Tubular Dysfunction in Sickle Cell Disease(2013) SILVA JUNIOR, Geraldo B.; VIEIRA, Ana Patricia F.; BEM, Amanda X. Couto; ALVES, Marilia P.; MENESES, Gdayllon C.; MARTINS, Alice M. C.; SANCHES, Talita R.; ANDRADE, Lucia C.; SEGURO, Antonio C.; LIBORIO, Alexandre B.; DAHER, Elizabeth F.Background/Aims: Kidney abnormalities are one of the main chronic complications of sickle cell disease (SCD). The aim of this study is to investigate the occurrence of renal tubular abnormalities among patients with SCD. Methods: This is a prospective study with 26 SCD adult patients in Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2), after a 12h period of water and food deprivation. Fractional excretion of sodium (FENa), transtubular potassium gradient (TTKG) and solute free water reabsorption (TcH2O) were calculated. The SCD group was compared to a group of 15 healthy volunteers (control group). Results: Patient`s average age and gender were similar to controls. Urinary acidification deficit was found in 10 SCD patients (38.4%), who presented urinary pH > 5.3 after CaCl2 test. Urinary osmolality was significantly lower in SCD patients (355 +/- 60 vs. 818 +/- 202mOsm/kg, p= 0.0001, after 12h period water deprivation). Urinary concentration deficit was found in all SCD patients (100%). FENa was higher among SCD patients (0.75 +/- 0.3 vs. 0.55 +/- 0.2%, p= 0.02). The TTKG was higher in SCD patients (5.5 +/- 2.5 vs. 3.0 +/- 1.5, p= 0.001), and TcH2O was lower (0.22 +/- 0.3 vs. 1.1 +/- 0.3L/day, p= 0.0001). Conclusions: SCD is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating and incomplete distal acidification defect. There was also an increase in the potassium transport and decrease in water reabsorption, evidencing the occurrence of distal tubular dysfunction.
conferenceObject TUBULOGLOMERULAR EVALUATION IN VISCERAL LEISHMANIASIS BEFORE AND AFTER TREATMENT WITH PENTAVALENT ANTIMONIAL(2014) OLIVEIRA, Michelle J. C.; SILVA JUNIOR, Geraldo; SAMPAIO, Aline M.; MONTENEGRO, Barbara; ALVES, Marilia P.; HENN, Guilherme A. L.; ROCHA, Hermano A. L.; MENESES, Gdayllon C.; MARTINS, Alice M. C.; SANCHES, Talita R.; ANDRADE, Lucia C.; SEGURO, Antonio C.; LIBORIO, Alexandre B.; DAHER, Elizabeth F.- Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled trial(2019) SILVEIRA, Marcelo Augusto Duarte; TELES, Flavio; BERRETTA, Andressa A.; SANCHES, Talita R.; RODRIGUES, Camila Eleuterio; SEGURO, Antonio Carlos; ANDRADE, LuciaBackgroundChronic kidney disease (CKD) is a public health problem worldwide, and proteinuria is a well-established marker of disease progression in CKD patients. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties, as well as having been shown to have an antiproteinuric effect in experimental CKD. The aim of this study was to evaluate the impact of Brazilian green propolis extract on proteinuria reduction and the changes in the estimated glomerular filtration rate (eGFR).MethodsThis was a randomized, double-blind, placebo-controlled study including patients with CKD caused by diabetes or of another etiology, 18-90years of age, with an eGFR of 25-70ml/min per 1.73m(2) and proteinuria (urinary protein excretion >300mg/day) or micro- or macro-albuminuria (urinary albumin-to-creatinine ratio>30mg/g or>300mg/g, respectively). We screened 148 patients and selected 32, randomly assigning them to receive 12months of Brazilian green propolis extract at a dose of 500mg/day (n=18) or 12months of a placebo (n=14).ResultsAt the end of treatment, proteinuria was significantly lower in the propolis group than in the placebo group695mg/24h (95% CI, 483 to 999) vs. 1403mg/24h (95% CI, 1031 to 1909); P=0.004independent of variations in eGFR and blood pressure, which did not differ between the groups during follow-up. Urinary monocyte chemoattractant protein-1 was also significantly lower in the propolis group than in the placebo group58pg/mg creatinine (95% CI, 36 to 95) vs. 98pg/mg creatinine (95% CI, 62 to 155); P=0.038.ConclusionsBrazilian green propolis extract was found to be safe and well tolerated, as well as to reduce proteinuria significantly in patients with diabetic and non-diabetic CKD.Trial Registration.(ClinicalTrials.gov number NCT02766036. Registered: May 9, 2016).