Vitamin C and epigenetics: A short physiological overview

In recent years, ascorbic acid (vitamin C) has acquired great interest due to its multiple functions, which results in homeostasis of normal tissues and organs. On the other hand, it has been shown that epigenetic modifications may have an important role in various diseases and therefore are a focus of the extraordinary investigation. Ascorbic acid serves as a cofactor for ten-eleven translocation dioxygenases, which are responsible for deoxyribonucleic acid methylation. Also, vitamin C is required for histone demethylation, since it acts as a cofactor of Jumonji C-domain-containing histone demethylases. It seems that vitamin C may be a mediator between the environment and the genome. The precise and multistep mechanism of ascorbic acid in epigenetic control is still not definitely determined. This article intends to provide the basic and newly discovered functions of vitamin C that are related to epigenetic control. Also, this article will help us to better understand the functions of ascorbic acid and will provide the possible implications of this vitamin in the regulation of epigenetic modifications

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

A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery

Introduction. The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). Purpose. The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). Materials and Methods. We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. Results. During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). Conclusion. We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment

CARDIAC RESYNCHRONIZATION THERAPY WITH OR WITHOUT AN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IN DIFFERENT GROUPS OF HEART FAILURE PATIENTS

Aim. Patients with heart failure have poor prognosis and mortality rate is between 15–60% per year. Implantable cardioverter-defibrillators and cardiac resynchronization therapy have been shown to improve survival, decrease hospital readmissions and mortality, and improve functional status and quality of life in patients with heart failure and left ventricular systolic dysfunction. Aim of the study was to examine the effects of different CRT devices in carefully selected heart failure patients during 1 year.Material and methods. We included 98 heart failure patients. First group (n=60) received CRT-P, while in second group (n=38) were patients with CRT-D pacemaker (with an additional cardioverter-defibrillator option).Results. Data gathered in our the study showed that both CRT-P and CRT-D in adequately selected heart failure patients improve different clinical parameters: symptoms, echocardiographic parameters, decrease QRS duration, increase 6 min walk test distance, decrease mortality rate.Conclusion. Patients with both CRT-P and CRT-D showed improvement in heart failure symptoms and CRT had significant influence on disease prognosis during 1 year of follow up. Nevertheless we do not have the perfect criteria for selection of patients and their follow up after the device implantation. In patients with the rhythm disturbances CRT-D option is the right choice only if the patient has the indications for resynchronization therapy as well. This choice however depends on clinical judgment of the operator more than on strict protocols and guidelines which are necessary but we need more clinical trials to support current hypothesis

Foveal Avascular Zone in Normal Tension Glaucoma Measured by Optical Coherence Tomography Angiography

Aim. To measure diameter of foveal avascular zone (FAZ), FAZ area, and vessel density using Optical Coherence Tomography Angiography (OCT-A) in patients with normal tension glaucoma (NTG) and to establish the possible role of OCT-A in diagnosis and follow-up of patients with NTG. Methods. Twenty-one eyes of 21 patients with NTG and 30 eyes of 30 healthy subjects underwent complete ophthalmic examination as well as OCT-A on ZEISS AngioPlex. 3×3 macula scans were used to measure vertical, horizontal, and maximum diameter of FAZ by two graders. Mean values and interobserver variability were analyzed. Image J was used for analysis of FAZ area and vessel density. Results. Mean vertical diameter (t=5.58, p<0.001), horizontal diameter (t=3.59, p<0.001), maximum diameter (t=5.94, p<0.001), and FAZ area (t=5.76, p<0.001) were statistically significantly enlarged in the NTG group compared to those in the control group. Vessel density (t=-5.80, p<0.001) was statistically significantly decreased in the NTG group compared to that in the control group. Conclusion. OCT-A could have an important role in the future in diagnosis of patients with NTG. In patients with NTG, there is larger FAZ area, while the vessel density is reduced in comparison to the control group

Foveal Avascular Zone in Normal Tension Glaucoma Measured by Optical Coherence Tomography Angiography

© 2017 Maja Zivkovic et al. Aim. To measure diameter of foveal avascular zone (FAZ), FAZ area, and vessel density using Optical Coherence Tomography Angiography (OCT-A) in patients with normal tension glaucoma (NTG) and to establish the possible role of OCT-A in diagnosis and follow-up of patients with NTG. Methods. Twenty-one eyes of 21 patients with NTG and 30 eyes of 30 healthy subjects underwent complete ophthalmic examination as well as OCT-A on ZEISS AngioPlex. 3×3 macula scans were used to measure vertical, horizontal, and maximum diameter of FAZ by two graders. Mean values and interobserver variability were analyzed. Image J was used for analysis of FAZ area and vessel density. Results. Mean vertical diameter (t=5.58, p<0.001), horizontal diameter (t=3.59, p<0.001), maximum diameter (t=5.94, p<0.001), and FAZ area (t=5.76, p<0.001) were statistically significantly enlarged in the NTG group compared to those in the control group. Vessel density (t=-5.80, p<0.001) was statistically significantly decreased in the NTG group compared to that in the control group. Conclusion. OCT-A could have an important role in the future in diagnosis of patients with NTG. In patients with NTG, there is larger FAZ area, while the vessel density is reduced in comparison to the control group

IMPLANTATION OF AN ICD AND DFT TESTING IN PATIENT WITH PERSISTENT LEFT SUPERIOR VENA CAVA

Aim. The implantable cardioverter-defibrillator [ICD] has been proven to reduce the risk of sudden cardiac death through the termination of ventricular fibrillation and life-threatening ventricular tachycardia. The simplest measure of defibrillation effectiveness is the DFT, defined as the lowest delivered shock strength required to defibrillate. Improved technology and use of ICDs for primary prevention have led some to question the need for either defibrillation testing or any assessment of defibrillation efficacy after implantation. Experts disagree about optimal testing because data are insufficient to define the trade-off between accuracy and risk of testing. However there are specific cases in which DFT is necessary.Material and methods. Authors describe the case of a patient with persistent left vena cava, a rare congenital anomaly, with no clinical importance which is usually accidentally revealed during the implantation of pacemaker or when placing a central vascular catheter. However, it represents a major problem and challenge for positioning of the standard pacemaker electrodes.Results. After a successful implantation via unconventional anatomic path authors carried out DFT testing to check that the device is functioning appropriately.Conclusion. Persistent left vena cava should not represent a contraindication for implantation of complex pacemaker systems such as ICD and DFT testing is advisable in this cases

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

© 2020, The Author(s). Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e′ ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3