ABSTRACT
Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT) and is associated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Serum serotonin regulation has been linked to pulmonary vascular function and disease, and serotonin transporter (SERT) is thought to be one of the key regulators in these processes. We sought to find evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV. Methods. We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human fetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene promoter defect in ACD/MPV patients. Results. We found that SERT protein expression begins at 30 weeks of gestation, increases to term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration. Conclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation at birth and plays a key role in the pathobiology of ACD/MPV.
Subject(s)
Lung/metabolism , Persistent Fetal Circulation Syndrome/etiology , Serotonin Plasma Membrane Transport Proteins/metabolism , Adaptation, Physiological , Female , Humans , Infant , Infant, Newborn , Lung/embryology , Male , Persistent Fetal Circulation Syndrome/metabolism , Promoter Regions, Genetic , Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/geneticsABSTRACT
Chagas disease is characterized by cardiac lesions and a high level of PGE2. Our objective was to investigate the role of PGE2 in cardiac lesions. BALB/c mice were infected with Trypanosoma cruzi (1x10(3) trypomastigote forms) and were treated daily with PBS, meloxicam (0.5 mg/kg) or etoricoxib (0.6 mg/kg). The animals were sacrificed on the 21st day of infection and we collected the cardiac tissue and spleen cells for tissue culture. We observed that treatment with COX-2 inhibitors was able to decrease synthesis of PGE2 by spleen cells. This reduction was accompanied by reduction of the inflammatory infiltrate, parasite nets, cardiac fibrosis and fewer COX-2 positive cells in cardiac tissue obtained from these animals. In conclusion, treatment with COX-2 inhibitors, and consequent inhibition of PGE2 synthesis, was able to reduce the cardiac damage observed during the acute phase of experimental Chagas disease, thus demonstrating the involvement of this mediator in the cardiac lesion.
Subject(s)
Chagas Disease/immunology , Dinoprostone/physiology , Trypanosoma cruzi/immunology , Acute Disease , Animals , Cells, Cultured , Chagas Disease/drug therapy , Chagas Disease/pathology , Cyclooxygenase 1/analysis , Cyclooxygenase 2/analysis , Cyclooxygenase Inhibitors/therapeutic use , Dinoprostone/biosynthesis , Etoricoxib , Fibrosis , Male , Meloxicam , Mice , Mice, Inbred BALB C , Myocardium/enzymology , Myocardium/pathology , Parasitemia/drug therapy , Parasitemia/parasitology , Prostaglandins/analysis , Pyridines/therapeutic use , Spleen/chemistry , Spleen/cytology , Sulfones/therapeutic use , Thiazines/therapeutic use , Thiazoles/therapeutic useABSTRACT
Angiosarcomas are rare tumors in children, usually occurring in soft tissue and liver. By contrast, angiosarcoma in adults usually occurs in the extremities in conjunction with lymphedema. Mesenteric angiosarcoma has only rarely been reported. When angiosarcomas arise in this location, they usually represent a 2nd malignancy following Hodgkin's lymphoma. We report a child who presented to the emergency room with an acute abdomen and underwent emergency surgery for a mesenteric angiosarcoma with associated lymphangiectasia of the bowel and mesentery. A brief review of the literature and the nomenclature of these unusual tumors are discussed.
