Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Everolimus has been successfully used in solid organ transplantation, especially of the heart and kidney, but much less often in lung transplantation. The aim of this study was to evaluate the efficacy and safety of long-term use of everolimus in lung transplantation in Chile. We retrospectively analyzed patients receiving everolimus between 2005 and 2010 in terms of indication, lung and kidney function, rejection episodes, infections, malignancy appearance, and adverse events. Ten of 60 lung transplant recipients were converted to everolimus (16%) at some point after transplantation: four due to calcineurin inhibitor nephropathy (RD); four bronchiolitis obliterans syndrome (BOS); one lymphoma; and one, graft pulmonary fibrosis. Among patients with RD, at a mean follow-up of 25 months (range = 3-60), renal function remained stable with baseline of 42.7 mL/min and final creatinine clearance of 45.7 mL/min; lung function did not deteriorate. BOS patients, with an average of 30 months' follow-up (range = 12-48), showed baseline forced expiratory volume in the first second of 49% (r: 41-57) without variation in three patients, but with a decrease in another one after 12 months. One patient discontinued everolimus due to intolerance after 1 year. Two patients developed neoplasias: skin cancer and multiple myeloma. There were 14 infection episodes in seven patients, including 10 involving the respiratory tract infections. Only one patient developed dyslipidemia after everolimus initiation. Two patients died: one due to multiple myeloma and another to BOS. There was no rejection episode. Everolimus was effective and safe when used in combination with low doses of calcineurin inhibitor over long-term follow-up of lung transplant patients.
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PMID:Long-term use of everolimus in lung transplant patients. 2183 61

Nitric oxide (NO) is synthesized by three distinct NO synthases (neuronal, inducible, and endothelial NOSs), all of which are expressed in almost all tissues and organs in humans. The regulatory roles of NOSs in vivo have been investigated in pharmacological studies with non-selective NOS inhibitors. However, the specificity of the inhibitors continues to be an issue of debate, and the authentic significance of NOSs is still poorly understood. To address this issue, we generated mice in which all three NOS genes are completely disrupted. The triple NOSs null mice exhibited cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced EDHF responses, with a shorter survival. The triple NOSs null mice also displayed metabolic abnormalities, including metabolic syndrome and high-fat diet-induced severe dyslipidemia. Furthermore, the triple NOSs null mice showed renal abnormalities (nephrogenic diabetes insipidus and pathological renal remodeling), lung abnormalities (accelerated pulmonary fibrosis), and bone abnormalities (increased bone mineral density and bone turnover). These results provide evidence that NOSs play pivotal roles in the pathogenesis of a wide variety of disorders. This review summarizes the latest knowledge on the significance of NOSs in vivo, based on lessons learned from experiments with our triple mutant model.
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PMID:Significance of nitric oxide synthases: Lessons from triple nitric oxide synthases null mice. 2570 17