CAMILLA FANELLI
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina
4 resultados
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- Alternative Cutaneous Substitutes Based on Poly(L-co-D,L-lactic acid-co-trimethylene carbonate) with Schinus terebinthifolius Raddi Extract Designed for Skin Healing(2019) KOMATSU, Daniel; HAUSEN, Moema A.; ERI, Ricardo Yugi; LEAL, Vinicius; PEDRINI, Flavia; YAKSIC, Camilo; ALVES, Thais F. R.; V, Marco Chaud; FANELLI, Camilla; NORONHA, Irene; DUEK, Eliana A. R.The search for new therapies and drugs that act as topical agents to relieve pain and control the inflammatory processes in burns always attracted interest in clinical trials. As an alternative to synthetic drugs, natural extracts are useful in the development of new strategies and formulations for improving the quality of life. The aim of this study was to develop a wound dressing using poly(L-co-D,L-lactic acid-co-trimethylene carbonate) (PLDLA-TMC) containing Schinus terebinthifolius Raddi (S.T.R.). S.T.R. is a native Brazilian plant known for its strong anti-inflammatory responses. The membrane of PLDLA-TMC + S. terebinthifolius Raddi was prepared at different concentrations of S.T.R. (5, 10, 15, and 50%). The Fourier transform infrared results showed no change in the PLDLA-TMC spectrum after S.T.R. addition, whereas the swelling test showed changes only in PLDLA-TMC + S.T.R. at 50%. The wettability measurements showed a mass loss due to the decrease in the contact angle in all samples after the S.T.R. addition in the polymer, whereas the S.T.R. release test showed a linear delivery pattern. The scanning electron microscopy analysis showed that S.T.R. was homogeneously distributed at only 5 and 10%. Tensile tests demonstrated an increase in Young's modulus and a reduction in the elongation till rupture of PLDLA-TMC after the addition of S.T.R. The biocompatibility in vitro evaluation with rat fibroblast cells seeded in the membranes of PLDLA-TMC + S.T.R. showed that although S.T.R. interfered in cell morphology, all concentrations tested showed that cells were able to adhere and proliferate during 7 days. Thus, S.T.R. at 50% was chosen to be tested for in vivo trials. The histological and immunohistochemistry results revealed an accelerated skin healing at 7 days after controlled secondary burns were introduced in the dorsal skin, with a striking total recovery of the epidermis and high rates of molecular activation of cell proliferation. Due to the known biocompatibility properties of PLDLA-TMC and its stable release of S.T.R., we strongly recommend S.T.R.-containing PLDLA-TMC as a curative device to favor skin healing.
- Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model(2019) REMPEL, Lisienny Campoli Tono; FAUSTINO, Viviane Dias; FORESTO-NETO, Orestes; FANELLI, Camilla; ARIAS, Simone Costa Alarcon; MOREIRA, Gizely Cristina da Silva; NASCIMENTO, Thalita Fabiana; AVILA, Victor Ferreira; MALHEIROS, Denise Maria Avancini Costa; CAMARA, Niels Olsen Saraiva; FUJIHARA, Clarice Kazue; ZATZ, RobertoHypoxia is thought to influence the pathogenesis of chronic kidney disease, but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates chronic kidney disease is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n = 54) or sham surgery (sham; n = 52). Twenty-six sham rats and 26 Nx rats remained in normoxia, whereas 26 sham rats and 28 Nx rats were kept in a normobaric hypoxia chamber (12% O-2) for 8 wk. Hypoxia was confirmed by immunohistochemistry for pimonidazole. Hypoxia was confined to the medullary area in sham + normoxia rats and spread to the cortical area in sham + hypoxia rats, without changing the peritubular capillary density. Exposure to hypoxia promoted no renal injury or elevation of the content of IL-1 beta or Toll-like receptor 4 in sham rats. In Nx, hypoxia also extended to the cortical area without ameliorating the peritubular capillary rarefaction but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury, and oxidative stress. The present study, in disagreement with current concepts. shows evidence that hypoxia exerts a renoprotective effect in the Nx model instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear and may involve NF-kappa B inhibition, amelioration of oxidative stress, and limitation of angiotensin II production by the renal tissue.
- 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.
- Mesenchymal Stromal Cells Induce Podocyte Protection in the Puromycin Injury Model(2019) ORNELLAS, Felipe Mateus; RAMALHO, Rodrigo J.; FANELLI, Camilla; GARNICA, Margoth Ramos; MALHEIROS, Denise M. A. C.; MARTINI, Sabrina Vargas; MORALES, Marcelo Marcos; NORONHA, Irene L.Podocytes are specialized cells with a limited capacity for cell division that do not regenerate in response to injury and loss. Insults that compromise the integrity of podocytes promote proteinuria and progressive renal disease. The aim of this study was to evaluate the potential renoprotective and regenerative effects of mesenchymal stromal cells (mSC) in a severe form of the podocyte injury model induced by intraperitoneal administration of puromycin, aggravated by unilateral nephrectomy. Bone derived mSC were isolated and characterized according to flow cytometry analyses and to their capacity to differentiate into mesenchymal lineages. Wistar rats were divided into three groups: Control, PAN, and PAN+ mSC, consisting of PAN rats treated with 2 x 10(5) mSC. PAN rats developed heavy proteinuria, hypertension, glomerulosclerosis and significant effacement of the foot process. After 60 days, PAN rats treated with mSC presented a significant amelioration of all these abnormalities. In addition, mSC treatment recovered WT1 expression, improved nephrin, podocin, synaptopodin, podocalyxin, and VEGF expression, and downregulated proinflammatory Th1 cytokines in the kidney with a shift towards regulatory Th2 cytokines. In conclusion, mSC administration induced protection of podocytes in this experimental PAN model, providing new perspectives for the treatment of renal diseases associated with podocyte damage.