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BASIC RESEARCH
Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model
Viviane Ferreira Paes e Silva, Rogerio Pazetti, Sonia de Fatima Soto, Mariana Moreira Quinhones Siqueira, Aristides Tadeu Correia, Fabio Biscegli Jatene, Paulo Manuel Pêgo-Fernandes
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paulo.fernandes@incor.usp.br

Tel.: 55-11-30695351
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Laboratory of Thoracic Surgery Research-LIM/61, Thoracic Surgery Department, Heart Institute (InCor), São Paulo, São Paulo/SP, Brazil.
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          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Mucociliary transport velocity &#40;MCTV&#41; from the left &#40;operated&#41; or right &#40;intact&#41; bronchi of rats treated with saline &#40;Sal&#41; or mycophenolate sodium &#40;MPS&#41; for 7&#44; 15&#44; or 30 days&#46; &#8727;Statistical differences between groups at each time point&#58; 7 days - Sal right <span class="elsevierStyleItalic">vs</span>&#46; Sal left&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;034&#59; 15 days - MPS right <span class="elsevierStyleItalic">vs</span>&#46; Sal right and <span class="elsevierStyleItalic">vs</span>&#46; MPS left&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;014 and <span class="elsevierStyleItalic">p&#60;</span>0&#46;001&#44; respectively&#59; 30 days &#8211; Sal left vs&#46; Sal right and MPS left&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;003 and <span class="elsevierStyleItalic">p &#61;</span> 0&#46;016&#44; respectively&#46; Behavior of groups over time&#58; Sal left 30 days <span class="elsevierStyleItalic">vs</span>&#46; 7 and 15 days&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;009 and 0&#46;005&#44; respectively&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Mycophenolate is currently one of the most commonly used immunosuppressive drugs in lung transplantation &#40;LTx&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;2</a> Mycophenolate is a cell cycle inhibitor that produces reversible noncompetitive blockade of the purine synthesis pathway enzyme type II isoform of inosine monophosphate dehydrogenase&#46;<a class="elsevierStyleCrossRefs" href="#bib3">3&#44;4</a> Although its pharmacokinetic properties are well defined&#44; the side effects of mycophenolate on respiratory epithelium&#44; and mucociliary clearance &#40;MCC&#41; in particular&#44; have yet to be studied&#46;</p><p id="para20" class="elsevierStylePara elsevierViewall">MCC is a first-line defense mechanism that protects the lungs from the accumulation of particles and pathogens by removing bacteria&#44; viruses&#44; antigens&#44; and toxins that are trapped in the mucus on the tracheobronchial airway surface&#46;<a class="elsevierStyleCrossRef" href="#bib5">5</a> An essential balance between mucus production and its removal by ciliated cells is required for optimal airway defense&#46;<a class="elsevierStyleCrossRef" href="#bib6">6</a></p><p id="para30" class="elsevierStylePara elsevierViewall">Many studies have reported that MCC is impaired in lung transplant patients&#46;<a class="elsevierStyleCrossRef" href="#bib5">5</a> Several features that are unique to LTx determine the predominance of fungal colonization and infections in the early postoperative period&#46; Perhaps one of the most important factors is the direct communication between the graft and the outside environment&#46; In addition&#44; blood supply to the anastomosis is disrupted&#44;<a class="elsevierStyleCrossRef" href="#bib7">7</a> causing chronic mild ischemia and placing the graft at high risk for infection&#46;<a class="elsevierStyleCrossRef" href="#bib8">8</a></p><p id="para40" class="elsevierStylePara elsevierViewall">In previous studies&#44; we showed that cyclosporine&#44;<a class="elsevierStyleCrossRefs" href="#bib9">9&#44;10</a> azathioprine&#44;<a class="elsevierStyleCrossRef" href="#bib11">11</a> and bronchial section<a class="elsevierStyleCrossRef" href="#bib12">12</a> can all impair MCC by decreasing ciliary activity and mucus production and secretion&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">We hypothesize that mycophenolate can also play an important role in impaired MCC in a bronchial section and anastomosis rodent model&#46; To test this hypothesis&#44; we analyzed the components of bronchial ciliated epithelium in immunosuppressed rats by measuring ciliary beat frequency &#40;CBF&#41;&#44; mucociliary transport velocity &#40;MCTV&#41;&#44; and mucus transportability &#40;MT&#41;&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">MATERIALS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Experimental design</span><p id="para60" class="elsevierStylePara elsevierViewall">Sixty male Wistar rats weighting 300 g were subjected to left bronchial section and anastomosis&#46; The right bronchus was used as an internal control&#46; Following surgery&#44; the rats were assigned to two groups that received either saline solution &#40;Sal group&#44; n &#61; 30&#41; or mycophenolate sodium &#40;MPS group&#44; n &#61; 30&#41;&#46; The animals were maintained according to the <span class="elsevierStyleItalic">Guide for the Care and Use of Laboratory Animals</span>&#44;<a class="elsevierStyleCrossRef" href="#bib13">13</a> and our institution&#39;s ethics committee approved the protocol&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Surgical procedure</span><p id="para70" class="elsevierStylePara elsevierViewall">Anesthesia was induced with inhaled isoflurane &#40;Isoforine&#44; Crist&#225;lia&#44; Itapira&#44; SP&#44; Brazil&#41; in a closed chamber&#44; followed by orotracheal intubation with a 14-gauge catheter that was 6&#46;5 cm in length&#46; General anesthesia was maintained by inhalation of 2&#37; isoflurane in pure oxygen via a nebulizer &#40;Model 1223&#59; Takaoka&#59; S&#227;o Paulo&#44; SP&#44; Brazil&#41;&#46; Ventilation was achieved by a volume-cycled ventilator &#40;Harvard Apparatus&#44; Holliston&#44; MA&#44; USA&#41; with a respiratory rate of 70 breaths&#47;min and a tidal volume of 10 ml&#47;kg&#46; A left thoracotomy was then performed&#46; The left main stem bronchus was dissected&#44; clamped&#44; and completely transected&#44; followed by an end-to-end anastomosis with continuous running 8-0 polypropylene sutures&#46; Finally&#44; airflow was restored&#44; and the atelectasis of the left lung was resolved by hyperinflation&#46; Prior to closing the incision&#44; a chest tube was inserted&#46; The chest tube and tracheal tube were removed immediately after spontaneous respiration was restored&#46; The surgical procedure was performed with the aid of a stereomicroscope at 8x the original magnification&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Therapy</span><p id="para80" class="elsevierStylePara elsevierViewall">Following surgery&#44; mycophenolate sodium &#40;Myfortic&#44; 180 mg&#44; Novartis&#44; Stein&#44; Switzerland&#41; was administered to the animals via an orogastric tube at a daily dosage of 400 mg&#47;m<span class="elsevierStyleSup">2</span>&#47;day diluted in saline&#46; The animals in the Sal group were subjected to the same therapeutic regimen but received only the vehicle &#40;saline&#41; in an equivalent volume&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Euthanasia</span><p id="para90" class="elsevierStylePara elsevierViewall">After 7&#44; 15&#44; or 30 days of treatment&#44; ten animals from each group were anesthetized with intraperitoneal sodium pentobarbital &#40;30 mg&#47;kg&#41; and sacrificed by exsanguination by section of the abdominal aorta&#46;<a class="elsevierStyleCrossRef" href="#bib14">14</a></p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Data collection</span><p id="para100" class="elsevierStylePara elsevierViewall">Immediately after the animals were sacrificed&#44; their lungs were removed <span class="elsevierStyleItalic">en bloc</span> from the thoracic cavity and placed in a petri dish&#46; After dissection&#44; an incision was made in each main bronchus&#44; and mucus collection was performed by inserting a small hair paintbrush into the lumen of each bronchus&#46; The mucus that adhered to the paintbrush was then placed in a 0&#46;6-ml microtube containing mineral oil &#40;to prevent dehydration&#41; and stored at -70 &#176;C&#46; MT was measured using an <span class="elsevierStyleItalic">in vitro</span> frog palate model&#46;<a class="elsevierStyleCrossRef" href="#bib15">15</a> The mucus&#44; which was previously defrosted at room temperature&#44; was placed on the frog palate ciliated epithelium&#44; and its movement was observed and timed with the aid of a stereomicroscope equipped with a reticulated eyepiece&#46; The MT of the rat mucus was compared to that of the frog mucus itself&#44; and the results are therefore expressed as relative velocity &#40;rat&#47;frog&#41;&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">After collection of the mucus sample&#44; the bronchi were placed under a light microscope &#40;Olympus&#44; BX50&#44; Tokyo&#44; Japan&#41; connected to a video camera &#40;Sony Trinitron&#44; 3CCD&#44; Tokyo&#44; Japan&#41;&#46; A stroboscope &#40;Machine Vision Strobe&#44; Cedarhurst&#44; NY&#41; was placed in front of the bronchi&#44; and CBF was measured by synchronization between cilia movement and a stroboscope flashlight&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">Finally&#44; under the same microscope&#44; <span class="elsevierStyleItalic">in situ</span> MCTV was measured by direct observation of particles deposited on the mucous layer moving across the bronchi&#46; The movement of the particles was timed&#44; and the velocity was registered as the distance covered over one minute&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Statistical analysis</span><p id="para130" class="elsevierStylePara elsevierViewall">All of the data were analyzed using the Statistic Package for Social Sciences &#40;SPSS version 13&#46;0&#41;&#46; An analysis of variance was used to test the interference and interaction of the factors&#46; Comparisons between groups were performed using the Bonferroni post-hoc test&#46; The results are expressed as mean&#177;SD&#44; and the differences were considered significance when <span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#46;</p></span></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">RESULTS</span><p id="para140" class="elsevierStylePara elsevierViewall">In the MT data collected from the rat mucus samples and tested in the frog palate model&#44; we found that neither mycophenolate sodium &#40;MPS&#41; nor bronchial section altered any transportability property for up to 30 days of treatment after surgery &#40;<span class="elsevierStyleItalic">p&#62;</span>0&#46;05&#59; <a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para150" class="elsevierStylePara elsevierViewall">With regard to the CBF measurements &#40;<a class="elsevierStyleCrossRef" href="#fig2">Figure 2</a>&#41;&#44; the left bronchi from MPS group showed a significant decrease on postoperative day 30 &#40;8&#46;47&#177;1&#46;12 Hz&#41; compared to day 7 &#40;10&#46;72&#177;1&#46;21 Hz&#44; <span class="elsevierStyleItalic">p&#60;</span>0&#46;001&#41; and day 15 &#40;9&#46;80&#177;1&#46;16 Hz&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;026&#41;&#46; In addition&#44; a significant decrease was also observed compared to the right bronchi from MPS group at 30 days &#40;9&#46;73&#177;0&#46;98 Hz&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;003&#41;&#46;</p><elsevierMultimedia ident="fig2"></elsevierMultimedia><p id="para160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In situ</span> MCTV &#40;<a class="elsevierStyleCrossRef" href="#fig3">Figure 3</a>&#41; was significantly slower in the MPS left group &#40;0&#46;021&#177;0&#46;009 mm&#47;min&#41; than in the Sal left group &#40;0&#46;038&#177;0&#46;023 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;016&#41; after 30 days&#46; The Sal left group showed an increase in MCTV compared to 7 &#40;0&#46;018&#177;0&#46;011 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;009&#41; and 15 days &#40;0&#46;017&#177;0&#46;013 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;005&#41; after the surgery and compared to the Sal right group at 30 days &#40;0&#46;023&#177;0&#46;018 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;003&#41;&#46; After 15 days of therapy&#44; MCTV in the MPS right group &#40;0&#46;038&#177;0&#46;017 mm&#47;min&#41; was higher than in the Sal right &#40;0&#46;018&#177;0&#46;016 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;014&#41; and MPS left &#40;0&#46;019&#177;0&#46;008 mm&#47;min&#44; <span class="elsevierStyleItalic">p&#60;</span>0&#46;001&#41; groups&#46; On postoperative day 7&#44; only the Sal left group showed MCTV impairment &#40;0&#46;018&#177;0&#46;011 mm&#47;min&#41; relative to the Sal right group &#40;0&#46;028&#177;0&#46;024 mm&#47;min&#44; <span class="elsevierStyleItalic">p &#61;</span> 0&#46;034&#41;&#46;</p><elsevierMultimedia ident="fig3"></elsevierMultimedia></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">DISCUSSION</span><p id="para170" class="elsevierStylePara elsevierViewall">In the present study&#44; we tested a drug that is commonly used as part of the immunosuppressant triple therapy regimen that consists of a corticosteroid &#40;prednisone&#44; prednisolone&#44; or methylprednisolone&#41;&#44; a calcineurin inhibitor &#40;cyclosporine or tacrolimus&#41;&#44; and an antimetabolite &#40;azathioprine or mycophenolate&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;2&#44;16&#44;17</a> We found that mycophenolate impairs MCC in the operated bronchi of animals treated for 30 days&#46; Consistent with our previous results&#44;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;12</a> MCC was also impaired by bronchial section for up to 15 days after surgery in saline-treated animals and showed significant recovery by postoperative day 30&#46; In the immunosuppressed animals&#44; however&#44; this was not the case&#46; These data partially corroborate our initial hypothesis and suggest that MPS might contribute to the high incidence of infection in the respiratory tract of lung transplant patients&#46;</p><p id="para180" class="elsevierStylePara elsevierViewall">Clinicians are continually searching for an adequate immunosuppressive regimen in an attempt to maximize efficacy against rejection while avoiding toxicity and infection&#46;<a class="elsevierStyleCrossRef" href="#bib17">17</a> Unfortunately&#44; the choice of the immunosuppressive regimen for an individual patient&#39;s requirements is usually reactive rather than proactive&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a> With respect to the optimal early and maintenance immunosuppression regimens&#44; a recent review showed a strong contrast between the wealth of evidence available in the renal transplant field and the paucity&#44; or at least a lack of consistency&#44; of information for LTx&#46;<a class="elsevierStyleCrossRef" href="#bib19">19</a> Several factors could explain this problem&#44; including the small sample sizes and often contradictory results of original studies of LTx and patients from a heterogeneous group of pulmonary diseases who receive lung transplants&#44; which results in widely varying patient phenotypes and individual pharmacogenomics&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a></p><p id="para190" class="elsevierStylePara elsevierViewall">Based on these difficulties&#44; the advantages of conducting studies using animal models are clear&#46; We believe that our bronchial section rodent model is useful for clarifying the adverse effects of immunosuppressive drugs on the respiratory epithelium&#44; specifically on mucociliary clearance&#46; We previously demonstrated that cyclosporine impaired both ciliary beat frequency and mucus production&#47;secretion for up to 90 days of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib9">9&#44;10</a> Conversely&#44; azathioprine caused a transiently perturbed on mucociliary transport on postoperative days 7 and 15&#44; and function was fully recovered in the animals that were treated for 30 days&#46;<a class="elsevierStyleCrossRef" href="#bib11">11</a> Together&#44; these results reflect the controversy we find in the literature regarding immunosuppression therapy for LTx&#44; even regarding drugs of the same class such as azathioprine and mycophenolate&#44; both of which are cell cycle inhibitors&#46;</p><p id="para200" class="elsevierStylePara elsevierViewall">The use of mycophenolate &#40;in place of azathioprine&#41; has increased since its commercialization and testing in renal and heart transplantation in the early 1990s&#46; Some studies suggest that mycophenolate may be more efficient than azathioprine at preventing acute rejection in LTx&#44; whereas the single prospective&#44; randomized study that compared these two drugs did not find any benefit&#46;<a class="elsevierStyleCrossRef" href="#bib18">18</a> Korom et al&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a> concluded in their review that there is currently no unambiguous evidence to support the superiority of mycophenolate over azathioprine in LTx that could justify its wide-scale use as a first-choice antimetabolite&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">Immunosuppression by mycophenolate occurs by virtue of its active component mycophenolic acid &#40;MPA&#41; through the inhibition of inosine monophosphate dehydrogenase &#40;IMPDH&#41;&#46; T and B cells are more dependent on this pathway than are other cells&#46; Other potential mechanisms of immunosuppression include inducing apoptosis in activated T cells&#44; decreasing the expression of adhesion molecules &#40;thereby decreasing the recruitment of inflammatory cells&#41;&#44; and decreasing the production of inducible nitric oxide and the resulting tissue damage&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a> Mycophenolate has also been shown to inhibit the proliferation of smooth muscle cells&#44; fibroblasts&#44; and endothelial cells by blocking DNA synthesis in the S phase of the cell cycle&#46;<a class="elsevierStyleCrossRef" href="#bib20">20</a></p><p id="para220" class="elsevierStylePara elsevierViewall">To our knowledge&#44; this is the first study to directly test the effects of mycophenolate on the mucociliary apparatus&#46; Furthermore&#44; we separately analyzed each of the two principal components of this clearance mechanism&#44; thereby showing that only cilia movement from the left &#40;sectioned&#41; bronchus was impaired after MPS therapy for 30 days&#46; By itself&#44; this treatment did not alter the viscoelastic properties of the mucus&#44; at least in the frog palate model employed here&#46;</p><p id="para230" class="elsevierStylePara elsevierViewall">There are several techniques for monitoring MCC&#44; the most common of which is the use of insoluble particles that can be directly observed&#44; primarily in humans&#44; through a bronchoscope&#44; by radiography or by external monitoring of radiolabelled particles&#46;<a class="elsevierStyleCrossRef" href="#bib21">21</a> In our rodent model&#44; we used a microscope equipped with a reticulated eyepiece&#44; which permitted the direct observation and timing of the progression of the particles trapped in the mucus layer across the bronchus&#46; Moreover&#44; we developed a setup consisting of an optic fiber connected to a stroboscope for analyzing CBF&#46;<a class="elsevierStyleCrossRef" href="#bib10">10</a> A limiting point in this setup is its dependence on an expert researcher to analyze and register CBF according to the frequency of the stroboscopic flashlight&#46; Finally&#44; we used the bullfrog palate&#44; a well-established method for analyzing the transportability of mucus samples&#46;<a class="elsevierStyleCrossRef" href="#bib15">15</a> Because of its similarity with mammalian respiratory epithelium&#44; we could test the transportability properties of the rat mucus samples in comparison with the autologous &#40;frog&#41; mucus&#46; We have thus accumulated a considerable amount of information regarding the physiological variability of mucociliary clearance as a result of the effects of various immunosuppressant agents&#46;<a class="elsevierStyleCrossRefs" href="#bib9">9&#8211;11</a></p><p id="para240" class="elsevierStylePara elsevierViewall">Presently&#44; we do not intend to analyze the intracellular mechanisms of action of MPS in the cells of the mucociliary system&#46; We can&#44; however&#44; infer from our results that MPS affects ciliated cells more than secretory &#40;goblet&#41; cells&#46; This is important for future studies that aim to avoid this undesirable side-effect of mycophenolate therapy on MCC&#46; Presumably&#44; the most informative method to study the mechanism of MPS is to use cultured respiratory epithelial cells&#46; Given that we observed a reduction in CBF&#44; we propose including a well-known ciliary stimulant such as extracellular adenosine triphosphate or acetylcholine<a class="elsevierStyleCrossRef" href="#bib22">22</a> when testing the effects of MPS&#46;</p></span></span>"
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          "titulo" => "INTRODUCTION"
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          "titulo" => "MATERIALS AND METHODS"
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              "titulo" => "Surgical procedure"
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              "titulo" => "Therapy"
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            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Euthanasia"
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              "identificador" => "cesec70"
              "titulo" => "Data collection"
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              "titulo" => "Statistical analysis"
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        3 => array:2 [
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          "titulo" => "RESULTS"
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        4 => array:2 [
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          "titulo" => "DISCUSSION"
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        5 => array:2 [
          "identificador" => "xack639207"
          "titulo" => "ACKNOWLEDGEMENTS"
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        6 => array:1 [
          "titulo" => "REFERENCES"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2011-04-07"
    "fechaAceptado" => "2011-05-06"
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          "clase" => "keyword"
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          "palabras" => array:4 [
            0 => "Immunosuppressive Agents"
            1 => "Lung Transplantation"
            2 => "Mucociliary Clearance"
            3 => "Animals"
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE&#58;</span><p id="spara40" class="elsevierStyleSimplePara elsevierViewall">To study the effects of mycophenolate sodium on mucociliary clearance&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">INTRODUCTION&#58;</span><p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation&#46; Although its pharmacokinetic properties are well defined&#44; its side effects on mucociliary clearance have not yet been studied&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">METHODS&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Sixty rats were subjected to left bronchial section and anastomosis&#46; The right bronchus was used as a control&#46; After surgery&#44; the rats were assigned to two groups based on whether they received saline solution &#40;n &#61; 30&#41; or mycophenolate sodium &#40;n &#61; 30&#41;&#46; After 7&#44; 15&#44; or 30 days of treatment&#44; 10 animals from each group were sacrificed&#44; and <span class="elsevierStyleItalic">in vitro</span> mucus transportability&#44; <span class="elsevierStyleItalic">in situ</span> mucociliary transport velocity and ciliary beat frequency were measured&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">RESULTS&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">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 &#40;<span class="elsevierStyleItalic">p&#62;</span>0&#46;05&#41;&#46; With regard to ciliary beat frequency&#44; the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 &#40;<span class="elsevierStyleItalic">p &#61;</span> 0&#46;003&#41;&#46; In addition&#44; we found a significant reduction in the <span class="elsevierStyleItalic">in situ</span> mucociliary transport velocity in the mycophenolate-treated group &#40;<span class="elsevierStyleItalic">p &#61;</span> 0&#46;0001&#41;&#46;</p></span> <span id="ceabs50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">DISCUSSION&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">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&#46; 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&#44; an important airway defense mechanism&#46;</p></span>"
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                      "titulo" => "Immunosuppressive therapy in lung transplantation&#58; state of the art"
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                              S Korom \n
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                        "tituloSerie" => "European Journal of Cardio-thoracic Surgery"
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                              M Sanford \n
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                              GM Keating \n
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        "texto" => "<p id="para250" class="elsevierStylePara elsevierViewall">This study was performed at the Thoracic and Cardiovascular Surgery Post-Graduation Program of Heart Institute of Clinics Hospital of S&#227;o Paulo University Medical School&#44; S&#227;o Paulo&#44; SP&#44; Brazil&#46; The study was supported by grants from The State of S&#227;o Paulo Foundation &#40;FAPESP&#41;&#44; S&#227;o Paulo&#44; SP&#44; Brazil&#46;</p>"
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Article information
ISSN: 18075932
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos