ABSTRACT
To test the potential role of heart-type fatty acid-binding protein [H-FABP] in detecting increased perioperative cardiac risk in comparison with cardiac troponin I [cTnI] in the early postoperative period. Sixty-seven patients who had clinical risk factors and underwent elective intermediate - or high-risk noncardiac surgery were included in this study. Serum specimens were analyzed for H-FABP and cTnI levels before and at 8 h after surgery. None of the patients had chest pain; 27 had a history of ischemic heart disease, 3 of heart failure, 5 of cerebrovascular diseases, 40 of diabetes and 46 of hypertension. The mean duration of the operations was 2.33 +/- 1.27 h [range 1-6]. In the postoperative period, 27 [40.3%] patients had increased H-FABP levels [>/=7.5 ng/ml]; the median preoperative serum H-FABP level was 0.13 ng/ml [<0.1-5.9] and the median postoperative H-FABP level was 6.86 ng/ml [<0.1-13.7]. Only 1 [1.5%] patient had cTnI >0.1 µg/l during the postoperative period. Correlation analysis revealed that the presence of diabetes was associated with an increased H-FABP level [r = 0.30, p = 0.01]. Of the 27 patients with H-FABP >/=7.5 ng/ml, 21 [87%] had diabetes. There was no significant correlation with other clinical risk factors, type or duration of surgery. The H-FABP levels significantly increased in the postoperative period. Most patients with increased postoperative H-FABP levels were diabetic. High H-FABP levels could alert clinicians to increased perioperative cardiovascular risk and could prevent underdiagnosis, especially in diabetic patients
ABSTRACT
OBJECTIVE: The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies. METHODS: Imatinib mesylate (50 microM), lithium chloride (100 microM), medroxyprogesterone acetate (200 microM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student's t-test. RESULTS: All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05). CONCLUSION: The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.