Effect of Amrinone, a Selective Inhibitor of Phosphodiesterase III, on PMNs-induced Cardiac Dysfunction in Ischemia/reperfusion

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at 25microM, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P< 0.001), and the maximal rate of development of left ventricular developed pressure (P< 0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of [Ca2+]i was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/ reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.

Expression of p(53) Gene in Laryngeal Squamous Cell Carcinomas: Correlation with HPV Infection and Clinicopathological Findings / 대한이비인후과학회지

BACKGROUND: Human papillomavirus(HPV) is epitheliotrophic virus invading the anogenital tract and the upper aerodigestive tract. HPV produces a diversity of benign and malignant tumors. The wild-type p(53) gene participates in suppressing cell transformation while the mutant forms have tumorigenic potential. Alterations in the structure of p(53) gene represent one of the most common genetic changes associated with human cancers. OBJECTIVES: We evaluated the HPV infection and p(53) overexpression, and analyzed p(53) overexpression according to clinicopathological findings and HPV infection in laryngeal squamous cell carcinomas. MATERIALS AND METHODS: Thirty-nine cases of laryngeal squamous cell carcinomas and ten cases of laryngeal nodules were analyzed for the detection of HPV DNA by in situ hybridization technique and the detection of p(53) overexpression by immunohistochemical technique. RESULTS: 1) HPV DNA was detected in 10(25.6%), and p(53) overexpression was detected in 19(48.7%) out of 39 cases in laryngeal squamous cell carcinomas. 2) The p(53) overexpression was detected in 7(78%) out of 9 cases more than Brinkman index score 1000, and was detected in 12(40%) out of 30 cases less than 1000. 3) HPV positive cases showed 50% of p(53) overexpression whereas HPV negative cases showed 48% overexpression. CONCLUSION: HPV and p(53) gene were thought to be the etiological factors of laryngeal squamous cell carcinomas. The p(53) overexpression was related to smoking regardless of the histopathological findings and HPV infection.