SONIA DE FATIMA SOTO YOSHIDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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conferenceObject Side effects of tacrolimus upon airway epithelial tissue(2013) SILVA, Maristela Prado e; SOTO, Sonia; ALMEIDA, Francine; LIMONETE, Tatiana; PARRA, Edwin; PEGO-FERNANDES, Paulo; JATENE, Fabio; PAZETTI, RogerioconferenceObject Comparison of two immunosuppressant triple therapies on airway mucociliary clearance in rats(2012) SILVA, Maristela Prado e; SOTO, Sonia; ALMEIDA, Francine; LIMONETE, Tatiana; PARRA, Edwin; PEGO-FERNANDES, Paulo; JATENE, Fabio; PAZETTI, Rogerio- Immunosuppression Effects on Airway Mucociliary Clearance: Comparison Between Two Triple Therapies(2013) SILVA, Maristela Prado e; SOTO, Sonia F.; ALMEIDA, Francine M.; LIMONETE, Tatiana T. K.; PARRA, Edwin R. C.; JATENE, Fabio B.; PEGO-FERNANDES, Paulo M.; PAZETTI, RogerioBackground. Tacrolimus and mycophenolate have now become the most widely used combination for maintenance immunosuppressive regimens after lung transplantation in comparison with cyclosporine and azathioprine. However, limited information is available with respect to their effects on cells, other than those from the immunologic compartment. We hypothesized that different triple therapies could have different effects on airway mucociliary clearance, playing an important role in respiratory infections observed after lung transplantation. Methods. Ninety rats were assigned to three groups (n = 30 each): control = vehicle, therapy 1 = tacrolimus + mycophenolate + prednisone, and therapy 2 = cyclosporine + azathioprine + prednisone. After 7, 15, or 30 days of treatment by gavage, the animals were killed and the following parameters were studied: mucus transportability, ciliary beating frequency, mucociliary transport velocity, and neutral and acid mucus production. Results. There was a significant decrease in ciliary beating frequency, mucociliary transport velocity, and neutral mucus production in all immunosuppressed animals; indeed, both therapies, mainly therapy 1, caused an increase in acid mucus production for as long as 15 days of treatment. Conclusions. Both triple therapies impaired airway mucociliary clearance of rats, but therapy 1 had a more deleterious effect. These data suggest that these undesirable effects can contribute to the high incidence of respiratory infections observed in patients undergoing lung transplantation. (C) 2013 by The Society of Thoracic Surgeons
- Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model(2011) SILVA, Viviane Ferreira Paes e; PAZETTI, Rogerio; SOTO, Sonia de Fatima; SIQUEIRA, Mariana Moreira Quinhones; CORREIA, Aristides Tadeu; JATENE, Fabio Biscegli; PEGO-FERNANDES, Paulo ManuelOBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.
conferenceObject Tacrolimus Causes Airway Mucociliary Clearance Impairment(2013) SILVA, M. P.; SOTO, S. F.; LIMONETE, T. T. K.; ALMEIDA, F. M.; JATENE, F. B.; PEGO-FERNANDES, P. M.; PAZETTI, R.Purpose: According to ISHLT Registry, the vast majority of lung transplant patients receive a tacrolimus-based maintenance immuno-suppressant therapy. However, its side effects on respiratory tract are not very well studied. We hypothesized that tacrolimus could impair airway mucociliary clearance. Methods and Materials: Twenty Wistar rats were assigned into two groups: Control (n¼10): saline solution; and TAC (n=10): tacrolimus (1 mg/kg/day). After 15 days of therapy by gavage, animals were killed and in situ mucociliary transport velocity (MCTV) and ciliary beating frequency (CBF) were measured by microscopic direct view of airway ciliated epithelium. Mucus production by goblet cells was quantified in periodic acid Schiff and alcian blue stained slides of the tracheobron-chial tissue. This study was support by São Paulo Research Foundation - Fapesp. Results: There was a significant decrease in MCTV (1.77 ± 0.50 and 0.73 ± 0.34 mm/min, Control and TAC, respectively, p<0.001) and CBF (15.06 ± 1.31 and 13.17 ± 1.47 Hertz, Control and TAC, respectively, p<0.001) in all TAC-treated animals. Indeed, tacrolimus caused an over production of mucus from airway goblet cells (12.78 ± 6.92 and 21.27 ± 7.86%, Control and TAC, respectively; p=0.007). Conclusions: Our study showed that TAC plays an important role on the impairment of the mucociliary clearance either by decreasing CBF and MCTV or by increasing mucus production. This impairment can be related with the high level of respiratory infection observed during the first 30 days after lung transplantation and must receive good attention from clinicians.