ABSTRACT
To investigate the pathogenesis of hyperlipidemia-related erectile dysfunction and the effects of DA-8159, a new phosphodiesterase-5 inhibitor, on protein expression, we performed a proteomic analysis of differentially expressed proteins in the corpus cavernosum of hyperlipidemic rats by two-dimensional electrophoresis-mass spectrometry. Rats were fed high-cholesterol diet and treated with 5 mg·kg(-1)·day(-1) DA-8159 concurrently. After 5 months apparent hyperlipidemia and significantly decreased maximal intra-cavernous pressure were observed in the control group with the alteration of 8 proteins, which were restored by DA-8159 treatment. The proteins whose levels decreased >2-fold and attenuated by DA-8159 were determined alcohol dehydrogenase, aldolase A, annexin 1, and tropomyosin-rat, whereas proteins increased>2-fold and recovered by DA-8159 were found to be aldehyde dehydrogenase complex, guanine deaminase, creatine kinase-B, and phosphoglycerate mutase type B subunit.
Subject(s)
Erectile Dysfunction/metabolism , Hyperlipidemias/complications , Penis/metabolism , Proteins/metabolism , Proteomics , Animals , Biomarkers/metabolism , Disease Models, Animal , Electrophoresis, Gel, Two-Dimensional , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Erectile Dysfunction/physiopathology , Male , Penile Erection , Penis/drug effects , Penis/physiopathology , Phosphodiesterase 5 Inhibitors/pharmacology , Proteomics/methods , Pyrimidines/pharmacology , Rats, Sprague-Dawley , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Sulfonamides/pharmacology , Time FactorsABSTRACT
Glucocorticoids (GC) remain the most commonly used agents for managing inflammatory rheumatic diseases. The adverse effects (AE) associated with high-dose GCs are well established, but there is a widespread misconception that AEs of high-dose GC therapy (>30 mg prednisone or equivalent daily) are similar in low-dose therapy (≤ 7.5mg prednisone equivalent a day). Although high-quality evidence on AEs of low-dose GC therapy is still lacking, risks and safety of low-dose GC therapy in rheumatic diseases are reviewed based on current evidence by category, including musculoskeletal, cardiovascular, infectious, gastrointestinal, neuropsychiatric, endocrine and metabolic, dermatologic, and ophthalmologic AEs. Recommendations concerning monitoring AEs with low-dose GC therapy are provided for each category of AEs on the basis of our literature review and clinical experience. There is emerging evidence that low-dose GCs are associated with a much lower level of AEs, which would allow their use over long periods in patients with rheumatic disease who gain clinical effectiveness and well-being from their use. Nonetheless, knowledge and understanding of AEs from low-dose GCs is vital to maximise benefits and minimise risks to patients.
