ONE-YEAR CARDIOVASCULAR OUTCOME IN PATIENTS ON CLOPIDOGREL ANTI-PLATELET THERAPY AFTER ACUTE MYOCARDIAL INFARCTION

The aim of this study was to determine the risk factors in patients on clopidogrel anti-platelet therapy after acute myocardial infarction, for cardiovascular mortality, re-hospitalization and admission to emergency care unit. We followed 175 patients on dual antiplatelet therapy, with clopidogrel and acetylsalicylic acid, for 1 year after acute myocardial infarction, both STEMI and NSTEMI. Beside demographic and clinical characteristics, genetic ABCB1, CYP2C19 and CYP2C9 profile was analyzed using Cox-regression analysis. End-points used were: mortality, re-hospitalization and emergency care visits, all related to cardiovascular system. During the accrual and follow-up period, 8 patients (4.6%) died, mostly as a direct consequence of an acute myocardial infarction. Re-hospitalization was needed in 27 patients (15.4%), in nine patients (33.3%) with the diagnosis of re-infarction. Thirty-two patients (18.3%) were admitted to emergency care unit due to cardiovascular causes, up to 15 times during the follow-up. NSTEMI was an independent predictor of all three events registered (mortality OR=7.4, p<0.05; re-hospitalization OR=2.8, p<0.05); emergency care visit OR=2.4, p<0.05). Other significant predictors were related to kidney function (urea and creatinine level, creatinine clearance), co-morbidities such as arterial hypertension and decreased left ventricular ejection fraction, as well as clopidogrel dosing regimen. As a conclusion, it may be suggested that one of the most significant predictors of cardiovascular events (mortality, re-hospitalization and emergency care visits) is NSTEMI. Besides, clopidogrel administration according to up-to-date guidelines, with high loading doses and initial doubled maintenance doses, improves 1-year prognosis in patients with AMI

PLACENTAL INSUFFICIENCY IN PREGNANCY AFTER 40th WEEK OF GESTATION

Pregnancy after the 40th week of gestation is often a great dilemma for obstetrician in diagnostic, therapeutic and in psychological terms as well. The aim of this study was to confirm the phenomenon of placental insufficiency in pregnancy after the 40th gestation week, the modality of delivery and perinatal outcome.The study comprised 3405 deliveries in a period of one year, 391 of which were terminated after the end of the 40th gestation week, including healthy pregnant women with singleton pregnancies. Control group included healthy pregnant women delivered between the 37th and 40th gestation week.The incidence of deliveries after the 40th week of gestation is 11.48%. Non-stress test was reactive in 99.65% of women in the study group. At the same time, CST (constriction– stress test) was assessed as negative in 78.67% of cases. The pathological CST was found in only 1.33% of cases. Doppler ultrasound measurements showed the increased resistance in umbilical artery flow in 3% of cases. Vacuum extraction was used for 16.62%of deliveries in the study group, and 8.73% of deliveries in the control group (χ2=23.24;p<0.001). In the study group, Caesarean section was performed in 14.58% of cases, and in control group in 9.07% (χ2=11.09; p<0.001).Placental insufficiency induced by duration of pregnancy is a rear phenomenon in uncompromised pregnancy. There was no significant difference in the morbidity and mortality rates between the study and control group

Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway

Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 μM) for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS) production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 μM) with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin