Quantitative analysis of selected genetic markers of induced brain stroke ischemic tolerance detected in human blood.

A brain stroke is a serious disease and the second leading cause of death in the European Union. Carotid stenosis accounts for 15% of all ischemic cerebral strokes. However, there is currently no effective screening for carotid disease. Analysis of the DNA from peripheral blood is increasingly being used for several disease diagnoses. The potentially beneficial therapeutic method of inducing tissue tolerance to ischemia has so far been studied mainly in animal models. The aim of this study is to investigate changes in the gene expression of selected markers of brain ischemia during carotid endarterectomy, considered in this study as an activator of ischemic tolerance. During the carotid endarterectomy, there is a short-term occlusion of the internal carotid artery. Using the RT-qPCR method, we detected changes in the early identified gene markers of brain ischemia (ADM, CDKN1A, GADD45G, IL6, TM4SF1) in peripheral blood during sub lethal cerebral ischemia caused by carotid endarterectomy. Patients underwenting surgical procedure were divided into three groups: asymptomatic, symptomatic, and those who underwent carotid endarterectomy after an acute stroke. The results were compared to a negative/control group. Carotid endarterectomy had an impact on the expression of all monitored biomarkers. We observed statistically significant changes (p value 0.05-0.001) when comparing the groups among themselves, as well as the presence of ischemic tolerance of brain tissue to ischemic attacks. In conclusion, ADM, GADD45G, and TM4SF1 were affected in symptomatic patients, GADD45G and IL6 in acute patients, and CDKN1A and ADM in asymptomatic group after application of carotid endarterectomy.

Endovascular repair as a rescue strategy to restoring the extracorporeal membrane oxygenation flow.

Ventricular septal defect (VSD) is a known complication after myocardial infarction associated with high mortality. Extracorporeal membrane oxygenation (ECMO) is being successfully used in patients with VSD as a bridge to definitive surgical repair. Although often the only possibility to stabilize hemodynamics and oxygenation, ECMO has many potential complications, carrying significant morbidity and mortality. Here, the patient presented with a postinfarct VSD on peripheral venoarterial ECMO who developed a dissection of the common iliac artery (CIA) on the 5th day after ECMO implantation. As a result, a sudden drop in ECMO flow has become evident along with high pressures in the arterial cannula. After a definitive diagnosis of a CIA lesion obstructing the blood flow was made, trans-ECMO endovascular repair of CIA was performed. Four days after endovascular repair, we encountered the same problem of decreased blood flow associated with stent kinking and were approached with another endovascular repair to re-establishing full ECMO flow.

Modifications of gene expression detected in peripheral blood after brain ischemia treated with remote postconditioning.

BACKGROUND: A stroke is an acute damage to a certain area of a nerve tissue of the brain. In developed countries, it ranks second among the most often causes of death and is also the leading cause of disability. Recent findings emphasize the significant neuroprotective effect of conditioning on the course and rate of recovery after ischemic attack; however the molecular mechanism of ischemic tolerance induced by conditioning is still not completely explored. METHODS AND RESULTS: The purpose of this study is an identification of changes in gene expression induced by stimulation of reaction cascades after activation of the neuroprotective mechanism using an experimental rat model of global ischemia. The induction of neuroprotective cascades was stimulated by the application of early and delayed form of remote ischemic postconditioning. The quantitative qRT-PCR method was used to assess the rate of change in ADM, BDNF, CDKN1A, CREB, GADD45G, IL6, nNOS, and TM4SF1 gene expression levels 72 h after ischemic attack. The detected results confirm the neuroprotective effect of both forms of postconditioning. Participation of neuroprotection-related gene expression changes was observed once as an early one (CREB, GADD45G), once as a delayed one (ADM, IL6), or both (BDNF, CDKN1A, nNOS, TM4SF1) postconditioning forms, depending on the particular gene. CONCLUSIONS: Our results characterize impact of ischemic tolerance on the molecular level. We predict ischemic tolerance to be consisted of complex combination of early and delayed remote postconditioning.

INTEGRATIVE MORPHOMETRIC CHARACTERISTIC OF ENDOTHELIAL DYSFUNCTION IN THE CASES OF CHILDREN WITH ESSENTIAL ARTERIAL HYPERTENSION.

OBJECTIVE: The aim: To optimize the treatment of children with Essential Arterial Hypertension (EAH) in assotiation with Endotelial Dysfunction (ED) by studying the clinical and morphofunctional characteristics of the cardiovascular system disorders and correction of endothelial dysfunction with the using of essential phospholipids. PATIENTS AND METHODS: Materials and methods: The study group consisted of 80 children and 30 - a control group. The next stage included the division of 80 children into 2 subgroups. Patients in the first subgroup received basic treatment (angiotensin-converting enzyme inhibitor of the third generation), the second - optimized treatment (basic treatment was with addition of certified drug lecithin). Doses were determined according to the instructions and age for 2 months. In the study were used: ECG, Echocardiography, Ultrasonography, Morphofunctional studies of the endothelium. RESULTS: Results: There is a dynamic decreasing in the level of left ventricular myocardial mass index (LV MMI), reduction of end-diastolic volume (EDV) and increase in the absolute values of shock volume (SV), ejection fraction( EF) under the influence of optimized treatment due to the inclusion of lecithin in the treatment of children with EAH with ED. The Ve/Va ratio had a tendency to increase. Vasoconstriction of vessels after the reactive hyperemia test was significantly reduced, but the degree of vasodilation varied depending on the method of therapy. The intima-media thickness (IMT) decreased in 1.12 times in the cases of children with an optimized treatment, accompanied by a decreasing of DEC by 2-times. Levels of the aortic stiffness index had a tendency of decreasing (from 0.88 ± 0.02 to 0.71 ± 0.01 and to 0.63 ± 0.01, respectively, by groups and in comparison with the control group - 0.55 ± 0 , 01), which reflects the improvement of hemodynamic parameters. The dynamic parameters obtained in the cases of patients with EAH in association with ED, taking into account the impact of the optimized treatment had positive correction on the total risk of cardiovascular complications, changes in the profile of LV diastolic filling, dysfunction of arterial endothelium. CONCLUSION: Conclusions: The inclusion of essential phospholipids in the treatment of children with EAH and ED helps to optimize the profile of LV diastolic filling and exclude vascular endothelial dysfunction and indicate a positive effect of optimized treatment on the overall risk of cardiovascular complications.

Interdisciplinary Management of Visceral Artery Aneurysms and Visceral Artery Pseudoaneurysms.

The paper presents the results of treating 14 patients, namely eight patients with visceral artery aneurysms and six patients with visceral artery pseudoaneurysms. In 64.3% of the patients, the initial diagnosis was made based on the ultrasound examination. All the patients (100%) underwent CT angiography, while angiography was performed in 71.4% of the cases. Five (35.7%) patients with visceral artery pseudoaneurysms were emergently hospitalized; among them, the signs of bleeding were observed in 2 patients. In 9 patients, pathology was detected during tests for other conditions. Five (35.7%) patients underwent endovascular treatment, while 9 (64.3%) patients received surgical treatment. Endovascular interventions and open surgery demonstrated a nil mortality rate. After endovascular treatment, stent thrombosis was found in 1 patient. In the case of surgical treatment, visceral artery aneurysm was observed in 1 patient who underwent the resection of superior mesenteric artery pseudoaneurysm. Conclusions. The choice of the method of treating visceral artery aneurysms and visceral artery pseudoaneurysms depends on the location, size, anatomic features of the visceral arteries and the clinical course of the disease. Both endovascular and surgical treatment demonstrate good postoperative outcomes. Visceral ischemia is one of the most serious complications in the postoperative period, which can complicate both the diagnosis and the choice of treatment tactics.

Detection of anti-infliximab antibodies in Slovak IBD patients and its costs saving effect.

OBJECTIVE: Management chronic inflammatory bowel disease (IBD) patients is associated with diagnosis, targeted treatment and and individual approach. There is a group of patients which loss the response to the biologic treatment caused by insufficient levels of biologics or positive antibodies against these drugs. This study was aimed to determine the prevalence of patients with positive antibodies against the biological treatment and the costs saving probabilities of the antibodies detection during the treatment. STUDY DESIGN: This retrospective study was based on examination of 183 IBD patients' sera (72 with Crohn's disease (CD) and 111 ulcerative colitis (UC)) treated with infiliximab. METHODS: Circulating serum infliximab concentrations and anti-infliximab antibodies (ATI) were quantified by ELISA methods. Costs associated with the treatment were analysed from the data of General Health Insurance Company, Slovakia. RESULTS: The average infliximab concentrations in groups of CD were 2.9 µg/mL, 38.9% of samples had a concentration ≤1 µg/mL. Group with UC had average infliximab levels of 3.19 µg/mL, 32.4% bellow ≤1 µg/mL. Positive ATI levels were detected in 52 patients, in 28 patients with CD (38.8%) and 24 patients with UC (21.6%). The average values of the antibodies were 387.75 U/ml in CD and 391.94 U/ml in UC group. More than 28% IBD patients were positive for ATI. After application of the results to the database of all IBD patients, finishing of the treatment with ATI could lead (after considering the ATI quantification costs) to possible annual savings of more than €2 million in Slovakian health-care system. CONCLUSIONS: Monitoring of infliximab and antibodies against infliximab and anti-TNF-α biologics may help optimize treatment strategies and costs for biological treatment.

Elevated Circulating PCSK9 Concentrations Predict Subclinical Atherosclerotic Changes in Low Risk Obese and Non-Obese Patients.

INTRODUCTION: Many studies have highlighted the important role of PCSK9 in the development of cardiometabolic changes and its possible function as a biomarker of myocardial infarction or ischemic heart disease. This study aimed to determine the relationship between circulating PCSK9 levels and subclinical vascular changes in the group of low risk patients without manifest cardiovascular diseases. METHODS: In this study, 120 healthy patients, free of manifest cardiovascular diseases, diabetes mellitus, and without lipid-lowering therapy, were divided into three groups based on BMI: normal weight (N = 50), overweight (N = 30), and obese (N = 40). Biochemical parameters, including basic lipid and non-lipid ones, were analyzed. PCSK9 levels were measured by ELISA, vascular changes were quantified by carotid ultrasound (carotid artery intima-media thickness, cIMT), and arterial stiffness parameters (pulse wave velocity, PWV; augmentation index, AI; stiffness parameter, ß) were measured by an echo-tracking method. RESULTS: Plasma levels of PCSK9 significantly increased in obese (172.78 ± 51.67 ng/mL) in comparison with overweight (120.14 ± 37.64, p < 0.001) and normal weight groups (114.92 ± 35.87, p < 0.001). Differences between the overweight and normal weight groups were not significant (p = 0.85). The level of PCSK9 significantly correlated with values of BMI (p < 0.001, r = 0.38). In addition to increase in laboratory parameters associated with moderate metabolic changes, significant increase in cIMT and parameters of vascular changes (ß, AI, PWV) were detected in groups with elevated BMI. Significant positive linear correlation of PCSK9 concentrations and cIMT (p < 0.001, r = 0.39), PWV (p < 0.001, r = 0.31), and ß (p < 0.001, r = 0.3) were found. In multivariable regression analysis after adjusting for gender, age, BMI, and LDL, the impact of PCSK9 on cIMT, ß, and PWV remained significant (p = 0.006, 0.03, and 0.002, respectively). CONCLUSION: PCSK9 plasma levels significantly correlated with subclinical vascular changes and their values were significantly elevated in obese subjects. We assume that PCSK9 could be used as a predictor of early vascular involvement, prior to the existence of manifest atherosclerosis. These results also highlight the role of anti-PCSK9 treatment in primary prevention.