ABSTRACT
BACKGROUND AND PURPOSE: Mucociliary malfunction occurs in chronic obstructive pulmonary disease (COPD) and compromised functions of ciliated bronchial epithelial cells may contribute to this. Cigarette smoke, a major risk factor for COPD, impairs ciliary beat frequency (CBF). cAMP augments CBF. This in vitro study addressed, in differentiated, primary human bronchial epithelial cells, whether roflumilast N-oxide, a PDE4 inhibitor, (i) augments CBF; (ii) prevents the reduction in CBF induced by cigarette smoke extract (CSE); and (iii) protects against the loss of the ciliated phenotype following long-term CSE exposure. EXPERIMENTAL APPROACH: Air-liquid interface cultured human bronchial epithelial cells were incubated with roflumilast N-oxide and exposed to CSE. CBF was assessed by digital high speed video microscopy (DHSV). Ciliated cells were characterized by ß-tubulin IV staining and analyses of Foxj1 and Dnai2 mRNA and protein (real-time quantitative PCR, Western blotting). KEY RESULTS: Roflumilast N-oxide concentration-dependently triggered a rapid and persistent increase in CBF and reversed the decrease in CBF following CSE. Long-term incubation of bronchial epithelial cells with CSE resulted in a loss in ciliated cells associated with reduced expression of the ciliated cell markers Foxj1 and Dnai2. The PDE4 inhibitor prevented this loss in the ciliated cell phenotype and the compromised Foxj1 and Dnai2 expression. The enhanced release of IL-13 following CSE, a cytokine that diminishes the proportion of ciliated cells and in parallel, reduces Foxj1 and Dnai2, was reversed by roflumilast N-oxide. CONCLUSION AND IMPLICATIONS: Roflumilast N-oxide protected differentiated human bronchial epithelial cells from reduced CBF and loss of ciliated cells following CSE.
Subject(s)
Aminopyridines/pharmacology , Benzamides/pharmacology , Bronchi/cytology , Cilia/physiology , Epithelial Cells/drug effects , Phosphodiesterase 4 Inhibitors/pharmacology , Smoke/adverse effects , Cell Differentiation , Cells, Cultured , Cilia/drug effects , Cyclopropanes/pharmacology , Epithelial Cells/cytology , Gene Expression Regulation/drug effects , Humans , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Tobacco Products/adverse effectsABSTRACT
OBJECTIVES: To investigate the recovery of pancreatic function after severe acute biliary pancreatitis (ABP), especially the influence of necrosectomy on endocrine and exocrine functions. METHODS: Prospective cohort study including 39 patients with severe ABP. According to need or no need for surgical necrosectomy, patients were further subdivided into 2 groups. Functional pancreatic evaluation was carried out 12 months after the ABP episode. Endocrine function was evaluated by an oral glucose tolerance test and exocrine function by fecal fat excretion, fecal chymotrypsin (FQ), and secretin-cerulein tests (SCT). RESULTS: Most of the patients with necrosectomy had an abnormal exocrine pancreatic function, with steatorrhea in 25%. In the group without surgery, exocrine function was pathologic in only 13.3% and there were no cases of steatorrhea. Endocrine function was pathologic in 75% of patients undergoing necrosectomy versus 26.7% in the nonoperated group. In this latter group, the patients with abnormal endocrine function did not require insulin therapy, while in 33.3% of patient in the necrosectomy group insulin was necessary. CONCLUSIONS: In our homogeneous series of severe ABP, necrosectomy impaired significantly pancreatic endocrine and exocrine function. On the other hand, most patients with the same origin and severity index, but without surgical debridement, maintained normal pancreatic function.
Subject(s)
Biliary Tract Diseases/complications , Pancreas/physiopathology , Pancreatitis, Acute Necrotizing/physiopathology , Aged , Blood Glucose/metabolism , Cohort Studies , Female , Glucose Tolerance Test , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatectomy , Pancreatic Function Tests , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/surgery , Prospective Studies , Severity of Illness IndexABSTRACT
OBJECTIVE: to assess whether a magnetic resonance cholangiopancreatography performed after an acute biliary pancreatitis leads to pancreatic morphological alterations and if secretin stimulation influences the visualization of the pancreatic tree. METHOD: forty patients with acute biliary pancreatitis, 25 female (62,5/) and 15 male (37,5/), 27 mild and 13 severe, were prospectively and consecutively studied. All patients had undergone cholecystectomy. No altered pancreatic functions were observed. Morphology of the pancreas and of the main pancreatic duct were assessed by magnetic resonance cholangiopancreatography five years after the episode of pancreatitis and a comparative study between patients and case controls was carried out. Secretin was given in 16 cases in whom the visualization of the duct was incomplete or absent. Ductal morphology before and after secretin stimulation was compared. RESULTS: significant differences were observed when the diameter and length of the main pancreatic duct were compared in patients and control cases and was completely visualized in 60% of the cases, and could be seen in all patients after secretin stimulation. The comparative statistical analysis of the length and diameter of the pancreatic duct before and after the secretin stimulation showed significant differences. CONCLUSION: acute biliary pancreatitis leads to morphological alterations, regarded as scar lesions which do not become chronic. Secretin stimulation improves the visualization of the main pancreatic duct.
Subject(s)
Pancreatic Ducts/pathology , Pancreatitis, Acute Necrotizing/pathology , Secretin/metabolism , Acute Disease , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Pancreas/pathology , Pancreatic Ducts/metabolism , Pancreatitis, Acute Necrotizing/metabolismABSTRACT
Objetivo: estudiar mediante la realización de colangiografía por resonancia magnética si tras la pancreatitis aguda de origen biliar se origina alteración de la morfología pancreática y si la administración de secretina influye en la visualización del árbol pancreático. Método: cuarenta pacientes con pancreatitis aguda biliar, fueron estudiados prospectiva y consecutivamente, 25 mujeres (62,5 por ciento) y 15 hombres (37,5 por ciento), 27 eran leves y 13 graves. Todos ellos colecistectomizados. Ninguno de los pacientes incluidos presentaba alteración de la función pancreática. Valoramos la morfología de la glándula pancreática y del conducto pancreático principal, con colangiografía por resonancia magnética a los cinco años del episodio de pancreatitis, realizando un estudio comparativo entre casos y controles. Administramos secretina en 16 casos en los que la visualización del conducto fue incompleta o nula, realizando un estudio comparativo de la morfología ductal antes y después de su administración. Resultados: se apreciaron algunas diferencias significativas al comparar el diámetro y la longitud del conducto pancreático principal de los casos y los controles; éste se visualizó de forma completa en el 60 por ciento de los casos, consiguiendo visualizarse en todos los pacientes tras la administración de secretina. El estudio estadístico comparativo de la longitud global y el diámetro del conducto pancreático antes y después de la administración de secretina, demostró que existían diferencias significativas. Conclusión: la pancreatitis aguda biliar origina alteraciones morfológicas, consideradas lesiones cicatriciales sin traducción hacia la cronicidad; la administración de secretina mejora la visualización del conducto pancreático principal (AU)
Subject(s)
Female , Male , Humans , Aged , Adult , Aged, 80 and over , Middle Aged , Pancreatic Ducts , Pancreatitis, Acute Necrotizing , Cholangiopancreatography, Endoscopic Retrograde , Magnetic Resonance Angiography , Secretin , Pancreas , Acute DiseaseABSTRACT
We report the results of a study performed in the thoracic surgery department of Hospital General Universitario of Valencia from October 1989 to December 1996. Of the 621 patients diagnosed of lung cancer during this period, 320 underwent the usual surgical excision, 18 were confirmed histologically as bronchial carcinoid tumors, indicating an incidence of 5.6% of all pulmonary neoplasms resected in our department. The symptoms most often reported were recurring infection (44.5%) and chest pain (33.3%). Only one patient presented carcinoid syndrome. The most common radiologic presentation was solitary pulmonary nodule (50%). The tumor was visible by fiberoptic bronchoscopy in 9 cases. Diagnosis was by bronchial biopsy in four cases. Confirmation was by immunohistochemical analysis of the specimen in all cases. Electron microscopy and immunohistochemical techniques using neuroendocrine panmarkers is considered fundamental for differentiating between neuroendocrine neoplasms and typical and atypical carcinoid tumors. Thirteen (72.2%) of the 18 patients studied were diagnosed of typical carcinoids and 5 (27.8%) of atypical carcinoids. Neuroendocrine marking showed neurospecific enolase in 15 patients and chromogranin positivity in 10.
