ROGERIO PAZETTI
Projetos de Pesquisa
Unidades Organizacionais
LIM/61 - Laboratório de Pesquisa em Cirurgia Torácica, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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Agora exibindo 1 - 9 de 9
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, 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
- Adverse Effects of Immunosuppressant Drugs upon Airway Epithelial Cell and Mucociliary Clearance: Implications for Lung Transplant Recipients(2013) PAZETTI, Rogerio; PEGO-FERNANDES, Paulo Manuel; JATENE, Fabio BiscegliOptimal post-transplantation immunosuppression is critical to the survival of the graft and the patient after lung transplantation. Immunosuppressant agents target various aspects of the immune system to maximize graft tolerance while minimizing medication toxicities and side effects. The vast majority of patients receive maintenance immunosuppressive therapy consisting of a triple-drug regimen including a calcineurin inhibitor, a cell cycle inhibitor and a corticosteroid. Although these immunosuppressant drugs are frequently used after transplantation and to control inflammatory processes, limited data are available with regard to their effects on cells other than those from the immunological system. Notably, the airway epithelial cell is of interest because it may contribute to development of bronchiolitis obliterans through production of pro-inflammatory cytokines. This review focuses the current armamentarium of immunosuppressant drugs used after lung transplantation and their main side effects upon airway epithelial cells and mucociliary clearance.
conferenceObject Histological analysis of compensatory lung growth effects in emphysematous rats after bilobectomy(2013) ALMEIDA, Francine Maria; SARAIVA-ROMANHOLO, Beatriz M.; PAULA, Rodolfo de; MORIYA, Henrique Takachi; LIGEIRO-DE-OLIVEIRA, Ana Paula; LOPES, Fernanda D. Q. S.; MAUAD, Thais; MARTINS, Milton de Arruda; PAZETTI, Rogerio- The impact of topically applied preservation solutions on the respiratory epithelium of tracheal grafts submitted to cold ischemia: functional and morphological analysis(2013) AZEVEDO-PEREIRA, Artur Eugenio de; SAKA, Juliana Akemi; OLIVEIRA-BRAGA, Karina Andrighetti de; PAZETTI, Rogerio; CANZIAN, Mauro; PEGO-FERNANDES, Paulo Manuel; JATENE, Fabio BiscegliOBJECTIVE: Advances in graft reepithelialization and revascularization have renewed interest in airway transplantation. This study aims to determine whether topically applied preservation solutions can ameliorate ischemic injury to tracheal grafts. We analyzed 1) the effects of cold ischemia on the mucociliary clearance of tracheal grafts and 2) the impact of topically applied preservation solutions on the effects of cold ischemia on mucociliary clearance. METHOD: Tracheal segments (n = 217) from 109 male Wistar rats were harvested, submerged in low-potassium-dextran-glucose, histidine-tryptophan-ketoglutarate, or saline solution (saline group), and stored at 4 degrees C for 6, 10, 16, or 24 hours. A control group (not submerged) was analyzed immediately after harvesting. In situ mucociliary transport and ciliary beating frequency were measured using a stroboscope. Epithelial integrity, cellular infiltration, and mucus storage were quantified by light microscopy and image analysis software, along with transmission electron microscopy. RESULTS: 1) The effects of cold ischemia: in situ mucociliary transport and ciliary beating frequency were greater in the control group than after cold ischemia. Microscopic analysis results were similar between groups. 2) The effects of preservation solutions: there was no difference between the low-potassium-dextran-glucose, histidine-tryptophan-ketoglutarate, and saline groups in functional or light microscopy analysis. The saline group presented stronger signs of ischemic injury with transmission electron microscopy. CONCLUSIONS: Cold ischemia diminished the mucociliary clearance of the tracheal respiratory epithelium. Topically applied preservation solutions did not ameliorate the injury caused by cold ischemia to the tracheal respiratory epithelium.
conferenceObject Compensatory lung growth effects on pulmonary mechanics of emphysematous rats after bilobectomy(2013) ALMEIDA, Francine Maria; SARAIVA-ROMANHOLO, Beatriz M.; VIEIRA, Rodolfo de Paula; MORIYA, Henrique Takachi; LIGEIRO-DE-OLIVEIRA, Ana Paula; LOPES, Fernanda D. T. Q. S.; MAUAD, Thais; MARTINS, Milton Arruda; PAZETTI, RogerioconferenceObject Creatine Supplementation Attenuates Pulmonary and Systemic Effects of Lung Ischemia-Reperfusion Injury(2013) VIEIRA, Rodolfo P.; ALMEIDA, Francine M.; PAZETTI, Rogerio; OLIVEIRA-JUNIOR, Manoel C.; LIGEIRO-OLIVEIRA, Ana Paula; MARTINS, Milton A.; DOLHNIKOFF, MarisaconferenceObject Creatine Supplementation Attenuates Pulmonary And Systemic Effects Of Lung Ischemia-Reperfusion Injury(2013) VIEIRA, R. P.; ALMEIDA, F. M.; OLIVEIRA-JUNIOR, M. C.; LIGEIRO-OLIVEIRA, A.; PAZETTI, R.; DOLHNIKOFF, M.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.