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The imbalance between vasoconstrictors and vasodilators may play an important role in the pathogenesis of erectile dysfunction (ED). A total of 36 patients with ED, organogenic [diabetic (n ¼ 12) and nondiabetic (n ¼ 12)] and psychogenic (n ¼ 12) etiology, and 12 healthy adult men as controls were included. The levels of endothelin-1 (ET-1), growth hormone (GH), angiotensinconverting enzyme activity (ACE), nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were determined in the flaccid penis cavernosal blood of patients and in cubital blood of patients and controls. In psychogenic ED, systemic ACE activity was elevated compared to controls (Po0.05). In diabetic and nondiabetic ED patients, systemic levels of ET-1 (Po0.0001 for both) and ACE activity (Po0.01 and o0.05) were higher while GH (Po0.0001 and o0.001), NO (Po0.0001 for both) and cGMP (Po0.01 for both) levels were lower compared to controls. In diabetic patients, systemic and cavernosal ET-1 levels (Po0.0001 for both) and cavernosal ACE activity levels (Po0.05) were significantly elevated while systemic and cavernosal NO (Po0.0001 for both) and GH (o0.001 and o0.05) levels were declined compared to psychogenic. In nondiabetic patients, systemic and cavernosal ET-1 levels (Po0.0001 for both) were significantly elevated while systemic and cavernosal NO (Po0.0001 for both) and systemic GH levels (Po0.05) were declined compared to psychogenic. Systemic NO was positively correlated with GH in psychogenic (r ¼ 0.616, Po0.05), diabetic (r ¼ 0.583, Po0.05) and nondiabetic (r ¼ 0.615, Po0.05) patients and correlated positively with cGMP (r ¼ 0.605, Po0.05) but negatively with ACE activities (r ¼ À0.585, Po0.05) in diabetic patients. In conclusion, plasma levels of ET-1, ACE activities are elevated and associated with reduction of GH, NO and cGMP levels in the systemic and cavernous blood of ED patients. This disturbance may indicate endothelial dysfunction that may hind at their significance in the pathophysiology of ED.

Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P<0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P<0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p<0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P<0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P<0.001 and r=0.76, P<0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P<0.001, r=0.64, P<0.001 and r=0.68, P<0.001 respectively). Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None