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Purpose: Primary Raynaud's phenomenon (PRP) is a vascular disorder characterized by recurrent vasospastic response of the fingers and toes to cold or stress. ATPsensitive potassium (KATP) channels are widely distributed in vasculatures, and play an important role in the vascular tone regulation. The major vascular isoform of KATP channels is composed of Kir6.1/SUR2 (KCNJ8/ABCC9). It would be important to determine whether variations of KATP genes related to PRP is thought to be associated with vasospasm. It is believed that the studies describing mechanisms involved in the pathogenesis of inherited vascular disorders offers the best opportunity for investigation of the early stages of pathogenicity and diagnosis of PRP and associated other diseases. In this study we aim to investigate possible association between genetic variations observed in KATP channel coding genes and vasospasm associated with PRP. Materials and Methods: In our study; the cases with PRP, the relation between the variation in the KCNJ8/ABCC9 genes (S422L/V734I or rs72554071/rs61688134) was examined. 50 subjects who were diagnosed with PRP (patient group) and 50 healthy subjects (control group) were included in the study. Variations were determined using the Tetra-Primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS PCR) method. Results: Of the individuals in the patient and control group included in the study, 21 were male and 29 were female. The mean age of the patients was 25.7±3.36 years, and the mean age of the control group was 25.9±3.44 years. No significant relationship was found between PRP disease and genotype and allele distribution of KCNJ8/ABCC9 genes. Conclusion: This study presented the first findings about KCNJ8/ABCC9 gene variations in the Turkish population and may lead to future studies. Studies involving a higher number of cases and more mutations will be able to show whether there is a relationship between KATP channels and PRP and contribute to the elucidation of PRP pathogenesis in terms of genetic factors. [ABSTRACT FROM AUTHOR]

Purpose: Ischemia/reperfusion (I/R)-induced injuries represent serious clinical events regarding profound target organ destructions followed by remote organ complications due to the loss of oxidant/antioxidant balance and apoptosis. Recent studies examining the mammalian target of rapamycin (mTOR) during I/R injury in different organs have remained a matter of debate. The current study aimed to explore further the protective and underlying antiapoptotic and antioxidant mechanisms of mammalian target of rapamycin (mTOR) inhibition in hindlimb (HL) schemia/reperfusion (I/R) injury. Materials and Methods: Occlusion of bilateral hindlimbs for 4 h with tourniquets was carried out under anesthesia to induce I/R for 4 h in rats. Rapamycin (1 mg/kg) or saline (4 mL/kg) was injected intraperitoneally 1 h before reperfusion. Gastrocnemius muscle, kidney, and blood were collected at the end of the experiments for analysis. Muscle and kidney damages were evaluated by measuring protein expression and/or phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4EBP1), ribosomal protein S6 (rpS6), B-cell lymphoma 2 (Bcl-2), caspase-3, and Bcl-2-associated X protein (Bax) with NADPH oxidase level and total antioxidant capacity in tissues or sera. Results: I/R-induced organ damages were demonstrated by enhanced phosphorylation and/or expression of rpS6, 4EBP1, caspase-3, and Bax with a significant reduction in Bcl-2 accompanied by a decreased total antioxidant capacity and increased level of NADPH oxidase. Administration of rapamycin, an inhibitor mTOR, protected against I/R-mediated injuries. Conclusion: Our findings suggest that the activation of mTOR signaling plays a crucial role in HL I/R-triggered organ damages presumably through the activation of apoptosis as a result of oxidant/antioxidant imbalance. [ABSTRACT FROM AUTHOR]

Purpose: We have previously demonstrated that activation of the mammalian target of rapamycin (mTOR)/inhibitory-κB-α/nuclear factor-κB p65 signaling pathway mediates organ injuries through increased oxidative/nitrosative stress and inflammatory response in rat models of hind limb ischemia/reperfusion (HL I/R). Following up our previous findings regarding I/R injury through mammalian target of rapamycin (mTOR), we aimed to focus on the possible interaction between mammalian target of rapamycin (mTOR and mitogen activated protein kinase kinase (MEK)1/extracellular signal-regulated kinase (ERK) 1/2 pathway in hind limb ischemia/reperfusion (HL I/R) resulting in target and remote organ injuries in the present study. Materials and Methods: Male Wistar rats were divided into four groups. HL I/R was induced by occluding with tourniquets of both hind limbs. Following 4 h, the tourniquets were removed following reperfusion for 4 h. After 4 h of reperfusion blood, kidney, and gastrocnemius muscle were collected. Results: HL I/R caused an increase in phosphorylation and/or expression of rpS6, MEK1, ERK1/2, tumor necrosis factor-α, inducible nitric oxide synthase, gp91phox, p22phox, and nitrotyrosine as well as nitrite levels in gastrocnemius muscle, kidney, and/or serum. Additionally, nicotinamide adenine dinucleotide phosphate oxidase and myeloperoxidase levels were increased in the tissues of rats subjected to HL I/R. Rapamycin, the selective inhibitor of mTOR, abolished all the effects mentioned above caused by HL I/R in the rat’s muscle and kidney. Conclusion: These data suggest that activation of the MEK1/ERK1/2 pathway contributes to mTOR-mediated HL I/R-induced target and remote organ injury. [ABSTRACT FROM AUTHOR]

Objective: One of the most frequently studied parameters in terms of outcome estimation in cardiac surgery is HbA1c. Several studies in literature suggest that high HbA1c value increases mortality and morbidity, but there is no relation between them. The primary aim of the present study is to investigate whether HbA1c value in diabetic patients undergoing coronary bypass graft surgery is an independent predictor for post-operative mortality and morbidity, and our secondary goal was to determine independent risk factors that cause mortality and morbidity in the same patient population. Methods: 380 diabetic patients diagnosed with diabetes who underwent coronary surgery with cardiopulmonary bypass in Mersin State hospital between July 2014 to December 2016 after the approval of the Mersin University Faculty of medicine ethics committee were included in this retrospective, observational, and cross-sectional study. Patient demographic and perioperative information were obtained from the electronic information operating system and from anesthesia-intensive care follow-up forms. The HbA1c threshold was accepted as 7%, which was reported to be more appropriate for evaluating high-risk groups. Results: Three hundred and fifty-four patients with complete access to the data were included in the study. The mean age of the patients was 60.8±9.4 years. 37% of the patients (131 patients) were female. The number of patients with HbA1c=7 was 194 (54,8%) in the entire patient population. In this study, high HbA1c (=7) values in diabetic patients undergoing isolated coronary bypass graft surgery were not found to be independent predictors of post-operative mortality and morbidity. Mortality was seen in 28 patients (7.9%). ejection fraction (EF) was found to be an independent predictor factor for pre-operative factors in logistic regression models constructed according to mortality predictors (OR:0.94; 95% CI: 0.90-0.99; p=0.016). Complications were seen in 50 patients (14.1%). In the models formed from the point of view of the complication predicators, only EF was found to be independent predictor (OR:0.95; 95% CI: 0.92-0.98; p=0.004). It was found that HbA1c was not predictive in all models for mortality and complication (p>0.05). Conclusion: There are reports in the literature that mortality increases 4-fold when HbA1c value is higher than 8.6% in coronary surgery. However, there is a view that HbA1c alone cannot predict mortality in coronary surgery if diabetes associated factors are excluded. In this study, high HbA1c (=7) values in diabetic patients undergoing isolated coronary bypass graft surgery were not found to be independent predictors of post-operative mortality and morbidity. Pre-operative low ejection fraction was found as an independent risk factor for post-operative mortality and morbidity in the general patient population. [ABSTRACT FROM AUTHOR]

Purpose: Ramipril is effective in treating inflammatory myocardial injury by reducing cytokines such as TNF-α, IL-6, and IL-8. In this study, we investigated the effect of cytokine gene polymorphisms on inflammatory response which might be reduced by ramipril. Material and Methods: Of 102 patients undergoing onpump coronary artery bypass grafting surgery, 51 were the treatment group which received ramipril and the remaining 51 were the non-treated control group. TNF-α, IL-6, a nd I L-8 were measured with Enzyme-Linked Immuno Sorbent Assay (ELISA), before anesthesia induction (t1), at 20 min following cross clamping (t2), at the end of the operation (t3), and 24 hours after anesthesia (t4). Genotyping was performed with PCR method. Results: While TNF-α increase began with surgery, IL-6 and IL-8 increase began with cardiac arrest during cardiopulmonary bypass and continued until the end of the operation. In contrast, only IL-8 remained high in the control group during the postoperative period, while TNF-α, IL-6, and IL-8 began to decrease. The decreases in IL-6 at t3 and in TNF-α at t4 were significant. Conclusion: Ramipril might have a role in preventing inflammatory myocardial injury by reducing cytokine and TnT levels after cardiac arrest. [ABSTRACT FROM AUTHOR]

Transfusion-related acute lung injury (TRALI) is the second leading cause of transfusion-associated mortality in high-risk patients undergoing major surgery. TRALI presenting with acute hypoxia and non-cardiac edema is a vital clinical entity which must be considered in the differential diagnosis in transfusion-associated patients. Fresh frozen plasma, erythrocyte suspension and thrombocyte suspension transfusion were performed during perioperative and postoperative periods to the patient undergoing supracoronary graft interposition due to ascending aortic aneurysm. Respiratory support treatment with positive pressure mechanical ventilation was initiated for acute hypoxia and bilateral pulmonary edema developed immediately after the procedure. The patient thought to have delayed TRALI was extubated on postoperative 5. day. Noninvasive mechanical respiratory support treatment was maintained. On postoperative 10. day the patient did not need any oxygen and ventilatory support. TRALI should be considered in patients with acute onset of hypoxia, ARDS especially in cases undergoing major surgery and transfusion of large amounts of ES, FFP, platelet suspension. Noninvasive mechanical ventilation should be considered as a treatment option. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. Methods: The study group ( n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril ( n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. Results: Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 ( p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant ( p < 0.05). However, differences between the groups were insignificant ( p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. Conclusion: Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism. [ABSTRACT FROM AUTHOR]

Abstract: In this study we aimed to investigate the vasorelaxant and antiatherogenic effects of the statins (fluvastatin and pravastatin) in the human saphenous vein grafts at the molecular level by using histopathologic, pharmacological and immunochemical techniques. The saphenous vein grafts evaluated histopathologically displayed a loss in their endothelium up to a ratio of 30% and set forth indications of functional deterioration. The pharmacological evaluations proved that the relaxation responses induced by fluvastatin and pravastatin were significantly inhibited by nitric oxide synthase inhibitor, NG-nitro-l-arginine, and cyclooxygenase inhibitor, indomethacin, while these responses were significantly increased by angiotensin converting enzyme inhibitors, captopril and enalapril, and rho kinase inhibitor, Y27632. The results of immunochemical studies are in accordance with the results of the pharmacological studies that the related statins increased the levels of nitric oxide, phospholipase A2 and they decreased the levels of angiotensin II and active rho kinase. On the other hand mevalonolactone, a substrate of lipid metabolism, failed to change the effects of fluvastatin and pravastatin in the related tissue. The experimental results indicate that activation of nitric oxide synthase and phospholipase A2-cyclooxygenase pathway and inhibition of angiotensin converting enzyme and rho kinase may have a role on the effects of fluvastatin and pravastatin in the human saphenous vein grafts. It seems that the vasorelaxant and antiatherogenic effects of the related statins are independent of their lipid lowering mechanism. [Copyright &y& Elsevier]

Objective: Cardiac valvular pathologies are frequently encountered as mechanical and functional disorders due to the calcification of the valves whatever the etiologies are. This pathophysiologic table usually ends up with valvular replacement. In this study we aimed to decrease/eliminate the calcium in the excised calcified human heart valves by using citric acid in vitro hence bringing about the question for possible oral treatment of calcification of the valves by citric acid ingestion. Methods: Fourteen pieces of mitral and/or aortic valves excised from 12 patients undergoing valve replacement were placed in a freshly prepared phosphate buffered saline solution containing 0.625% glutaraldehyde at +4 °C for 48 h. They were rinsed with 0.9% NaCl and divided into two groups; study and control. Control tissues were further treated in a freshly prepared solution with identical properties for another 5 days. Study tissues were placed into a solution containing 3.8% citric acid (pH 7.4) and kept for 48 h at +37 °C, then rinsed with 0.9% NaCl and transferred into a fresh solution containing 0.625% glutaraldehyde with phosphate buffer at 37 °C for 3 more days. Specimens were biochemically and histopathologically evaluated and compared using Mann Whitney U test. Results: Calcium and phosphate levels in the study group were lower than in the control group (852.5±913.41 µg g-1 vs 413.05±519.53 µg g-1, p=0.001 and 207.6±321.86 µg g-1 vs 124.4±289.48 µg g-1, p=0.035, respectively). Malondialdehyde and protein level values were changed insignificantly in the control and study groups. Histopathologic evaluation showed that collagen and elastin fibers were similar in both groups. In the study group, irregular and fusiform calcific formations around the collagen fibers were significantly decreased. Conclusions: Decalcifying human heart valves in vitro conditions with citric acid without an adverse change to the morphology of the valvular tissue specimens is meaningful. We believe that forwarding and looking for the answer to the question "whether systemic application of citric acid could lead to the decalcification and/or reduction of calcification in the native human heart valves" would be expressive. [ABSTRACT FROM AUTHOR]