Oxidative Stress Markers in Hypertrophic Cardiomyopathy.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to oxidative stress. The present study aimed to examine oxidative-antioxidant disturbances in patients with HCM compared with control individuals. Materials and Methods: We enrolled 52 consecutive HCM patients and 97 controls without HCM. The groups were matched for age, body mass index, and sex. Peripheral blood was collected from all patients to determine the total antioxidant capacity (TAC), total oxidant status (TOS), lipid hydroperoxide (LPH), and malondialdehyde (MDA). The oxidative stress index (OSI) was defined as the ratio of the TOS level to the TAC level. Results: The median age was 52 years, and 58.4% were female. The area under the curve (AUC) indicated good predictive power for the TAC and TOS [AUC 0.77 (0.69-0.84) and 0.83 (0.76-0.90), respectively], as well as excellent predictive power for the OSI [AUC 0.87 (0.81-0.93)] for HCM detection. Lipid peroxidation markers also demonstrated good predictive power to detect HCM patients [AUCLPH = 0.73, AUCMDA = 0.79]. Conclusions: The TOS, the TAC, LPH levels, and MDA levels have good predictive power for HCM detection. The holistic assessment of oxidative stress by the OSI had excellent power and could identify patients with HCM.

Remote Supervision to Decrease Hospitalization Rate (RESULT) study in patients with implanted cardioverter-defibrillator.

AIMS: The number of patients with heart failure (HF) and implantable cardiac electronic devices has been growing steadily. Remote monitoring care (RC) of cardiac implantable electronic devices can facilitate patient-healthcare clinical interactions and prompt preventive activities to improve HF outcomes. However, studies that have investigated the efficacy of remote monitoring have shown mixed findings, with better results for the system including daily verification of transmission. The purpose of the RESULT study was to analyse the impact of remote monitoring on clinical outcomes in HF patients with implantable cardioverter-defibrillator [ICD/cardiac resynchronization therapy-defibrillator (CRT-D)] in real-life conditions. METHODS AND RESULTS: The RESULT is a prospective, single-centre, randomized trial. Patients with HF and de novo ICD or CRT-D implantation were randomized to undergo RC vs. in-office follow-ups (SC, standard care). The primary endpoint was a composite of all-cause death and hospitalization due to cardiovascular reasons within 12 months after randomization. We randomly assigned 600 eligible patients (299 in RC vs. 301 in SC). Baseline clinical and echocardiographic characteristics were well-balanced and similar in both arms. The incidence of the primary endpoint differed significantly between RC and SC and involved 39.5% and 48.5% of patients, respectively, (P = 0.048) within the 12-month follow-up. The rate of all-cause mortality was similar between the studied groups (6% vs. 6%, P = 0.9), whereas hospitalization rate due to cardiovascular reasons was higher in SC (37.1% vs. 45.5%, P = 0.045). CONCLUSION: Remote monitoring of HF patients with implanted ICD or CRT-D significantly reduced the primary endpoint rate, mostly as a result of a lower hospitalization rate in the RC arm (ClinicalTrials.gov Identifier: NCT02409225).

Impact of Remote Monitoring on Long-Term Prognosis in Heart Failure Patients in a Real-World Cohort: Results From All-Comers COMMIT-HF Trial.

BACKGROUND: Randomized controlled trials demonstrate that remote monitoring (RM) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy devices (CRT-Ds) may improve quality of care and prognosis in heart failure (HF) patients. However, the impact of RM on long-term mortality in a real-world cohort is still not well examined. METHODS AND RESULTS: This study was designed as a matched cohort study based on the COMMIT-HF trial--a single-center, ongoing prospective observational registry (NCT02536443). Complete patient demographics, medical history, in-hospital results, hospitalizations, and mortality data were collected based on institutional registries and healthcare providers' records. Patients were divided into 2 groups based on RM presence and matched by means of propensity scores according to clinical characteristics. The primary endpoint of this study was the long-term all-cause mortality. Out of 1,429 consecutive patients, 822 patients with a first implantation of an ICD/CRT-D were included in the analysis. The final matched study population contained 574 patients in RM and in a control group. Although demographic and echocardiographic parameters as well as pharmacological treatments were similar in both groups, a significantly lower 1-year mortality was detected in the RM group (2.1% vs. 11.5%, P < 0.0001). This was also maintained during a 3-year follow-up (4.9% vs. 22.3%, P < 0.0001). Multivariate analysis showed that RM was associated with an improved prognosis (hazard ratio 0.187, 95% confidence interval 0.075-0.467, P = 0.0003). CONCLUSION: RM of HF patients with ICDs/CRT-Ds significantly reduced long-term mortality in a real-world clinical condition.

Hematological Alterations in Common Carp (Cyprinus carpio L.) Exposed to Herbicides: Pendimethalin and Ethofumesate Tested Separately and in Mixture.

Herbicides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to environmental safety. The aim of the present study was to investigate common carp hematological alterations caused by herbicide exposure. Fish were treated with pendimethalin and ethofumesate tested separately and in mixture administered to aquarium water. Peripheral blood of treated fish was collected after 1, 3 and 7 days of exposure and compared to control. The total number of erythrocytes (RBC), total number of leukocytes (WBC), hematocrit value (Hct), total hemoglobin concentration (Hb), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and leukograms were determined at once. The results indicate that herbicide exposure caused different changes in the hematological profile of the fish. In the case of exposure to individual herbicides, short-term fluctuations of various hematological indices were noted. Moreover, a significant increase in RBC and Hct after a short period of exposure (1-3 days) in fish exposed simultaneously to both tested herbicides was observed. Exposure to herbicides affected the leukocyte profile after 3 and 7 days of duration. Fluctuations of hematological parameters are a typical change in fish exposed to pesticides.

Elevated brain glucose and glycogen concentrations in an animal model of depression.

INTRODUCTION: Recent data indicate that there is a link between depression and diabetes and that excess glucocorticoids may play an underlying role in the pathogenesis of both of these diseases. The aim of the present study was to determine whether there are any alterations in glucose, glycogen, glucose transporters, insulin, insulin receptors or corticosterone concentrations in the hippocampus and frontal cortex in a prenatal stress rat model of depression. METHODS: Male rats whose mothers had been subjected to stress and control animals were subjected to the Porsolt test to verify the experimental model. Next, some of the rats were subjected to acute stress and/or were administered glucose. Glucose, glycogen, corticosterone, insulin, insulin receptor, phospho-insulin receptor and glucose transporter (GLUT1, GLUT3 and GLUT4) concentrations were assayed. RESULTS: Prenatally stressed rats exhibited glucose and glycogen concentrations in both investigated brain structures that exceeded those of the control animals. Prenatal stress also increased the levels of glucose transporters - GLUT1 in both tissues and GLUT4 in the frontal cortex. The changes in the prenatally stressed rats were more prominent in the animals that were subjected to stress or glucose loading in adulthood. CONCLUSION: The increase in carbohydrate brain concentrations evoked by prenatal stress may result from changes in the amounts of glucose transporters, especially GLUT1. Moreover, the obtained results support the hypothesis that stress during the perinatal period permanently increases the sensitivity of brain tissue to factors that act in adulthood. © 2014 S. Karger AG, Basel.

The effect of oleanolic and ursolic acids on the hemolytic properties and biofilm formation of Listeria monocytogenes.

Oleanolic acid and ursolic acid are pentacyclic triterpenoids isolated from a variety of medicinal plants, which have antibacterial activity. Listeria monocytogenes is a Gram-positive facultative pathogen, being the causative agent of listeriosis. The present study was carried out to evaluate the in vitro effect of sub-inhibitory concentrations of both triterpene acids on the pathogenicity determinants of L. monocytogenes: their hemolytic activity and biofilm forming ability. Oleanolic and ursolic acids inhibited listeriolysin O activity without influencing toxin secretion. Biofilm formation, and the viability of L. monocytogenes cells in biofilms was diminished by both compounds. Thus, both acids affected L. monocytogenes virulence. It was also demonstrated that oleanolic acid bound to the peptidoglycan of L. monocytogenes and this interaction was influenced by teichoic acids.

Red cell distribution width is associated with long-term prognosis in patients with stable coronary artery disease.

BACKGROUND: Data regarding the association between red cell distribution width (RDW) values and mortality in patients with stable coronary artery disease are scarce. We aimed to investigate the link between mortality and RDW in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We analyzed 2550 consecutive patients with stable coronary artery disease who underwent PCI between 2007 and 2011 at our institution. The patients were divided into four groups according to RDW quartiles. The association between the RDW values and the outcomes was assessed using Cox proportional regression analysis after adjusting for clinical, echocardiographic, hemodynamic and laboratory data in the whole population and in subgroups stratified by gender, presence of diabetes, anemia or heart failure. RESULTS: In the entire population, there was a stepwise relationship between RDW intervals and comorbidities. Patients with the highest RDW values were older and more often burdened with diabetes, heart failure and chronic kidney disease. There was an almost 4-fold increase in mortality during an average of 2.5 years of follow-up between the group of patients with RDW values lower than 13.1% (25th percentile) and the group with RDW values higher than 14.1% (75th percentile), (4.3% vs. 17.1%, p < 0.0001). After adjusting for the covariates, RDW remained significantly associated with mortality in the whole cohort (HR-1.23 [95% CI (1.13-1.35), p < 0.0001]) and in the subgroups stratified by gender, age (over and under 75 years), presence of anemia, diabetes, heart failure and chronic kidney disease. CONCLUSION: Higher RDW values correspond to higher comorbidity burdens and higher mortality. RDW is an independent predictor of mortality in patients with stable coronary artery disease.

Synergy between novel antimicrobials and conventional antibiotics or bacteriocins.

Due to the alarming spread of resistance to classic antimicrobial agents, innovative therapeutic methods to combat antibiotic-resistant bacterial pathogens are urgently required. This minireview examines the enhancement of antibiotic efficacy by their combination with new antimicrobials, such as plant-derived compounds, metal ions and nanoparticles and bacteriophage lytic enzymes. The mechanisms of the observed synergy are also described. The promising results of basic research indicate that in future, combined therapy may be applied in human and veterinary medicine, agriculture and the food industry to combat bacterial pathogens.

In vitro study of secreted aspartyl proteinases Sap1 to Sap3 and Sap4 to Sap6 expression in Candida albicans pleomorphic forms.

Transition from round budding cells to long hyphal forms and production of secreted aspartic proteases (Saps) are considered virulence-associated factors of Candida albicans. Although plenty of data dealing with Saps involvement in the infection process have been published, Saps expression by the different pleomorphic forms as well as the capacity of C. albicans filaments to express Sap1-6 under serum influence are poorly investigated. In this study, we used immunofluorescence and immunoelectron microscopy for the detection of Sap1-6 isoenzymes in C. albicans pleomorphic cells (blastoconidia, germ tubes, pseudohyphae, true hyphae) grown in Sap-inductive human serum and Sap non-inductive medium - yeast extract-peptone-glucose (YEPD). Isoenzymes were below the detection level in all blastoconidial cells grown in YEPD for 18 h. Sap1-6 expression was hardly detected in C. albicans cells cultivated in serum for 20 min. Increasing level of Sap1-6 expression was observed when C. albicans was incubated for 2, 6 and 18 h in serum corresponding to the development of germ tubes, pseudohyphae and true hyphae. The expression of Sap1-3 in pseudohyphae and true hyphae was more intensive compared to Sap4-6. Thus, we could show that human serum induced hyphae formation and the expression of Sap1-6 were co-regulated.

Is the last before-death alert remote monitoring transmission in patients with heart failure life-threatening?

BACKGROUND: Remote monitoring (RM) of cardiac implantable electronic devices (CIED) allows for a regular analysis of the occurrence of arrhythmias and functioning of the devices. AIMS: To date, no study investigated the characteristics of the alert-triggered ultimate transmissions before death, which was the aim of the present analysis. METHODS: Patients monitored remotely in our center, whose baseline characteristics were obtained from the COMMIT-HF Registry (NCT02536443) were analyzed and divided according to the occurrence of alert transmissions during the RM. In patients who had an alert transmission, the last transmission was analyzed. All RM data were obtained from the software provided by four RM manufacturers. RESULTS: Of 1271 patients with CIEDs which transmitted at least one message to the RM center, 198 (15.6%) had no alert transmissions, while 1073 (84.4%) had at least one alert transmission. Respective mortality in patients with and without alerts during RM was 29.7% and 12.6%, respectively. In patients who had ever an alert, the last recorded transmission before death was scheduled in 166 patients and alert-triggered in 152 patients. The most frequent alert-triggered last transmissions were atrial fibrillation/flutter (39.4%) and ventricular tachyarrhythmias (26.8%). The median period from the last alert-triggered transmission to death was 10 days. CONCLUSION: This is the first analysis of the ultimate RM transmissions delivered by CIEDs before death. In approximately 85% of RM patients with CIEDs, at least one alert transmission occurred during the RM, and in patients who had ever an alert, almost half of the last transmissions before death were alert-triggered.

The impact of complications related to transvenous lead extraction on the 12-month prognosis: Insights from the SILCARD registry.

BACKGROUND: Scant data exist on long-term outcomes, including death, in patients with complica-tions related to transvenous lead extractions (TLE). AIMS: We sought to characterize the population and examine the outcomes including risk factors for in-hospital complications and 12-month mortality and morbidity related to the complications in a large administrative database of patients undergoing TLE. RESULTS: From the database of patients hospitalized for cardiovascular diseases and included in the Silesian Cardiovascular Database (SILCARD) registry, we selected the admissions of those who underwent TLE according to the appropriate ICD-9 codes. The patients were divided into two groups based on whether they did or did not manifest any complications during their hospitalization for the TLE procedure. Between 2007 and 2019, we found a total of 835 patients who underwent TLE. TLE-related complications occurred in 56 patients (6.7%) of the Complications-Yes group while no complications were recorded in 779 (93.3%) patients of the Complications-No group. A significant difference in the rate of all-cause mortality (23.9% vs. 6.5%; P <0.001) and major adverse cardiac events (MACE) (58.7% vs. 39.4%; P = 0.01) between the Complications-Yes and Complications-No groups were recorded. Multivariable analysis of the entire study population revealed that prior dialysis, chronic kidney disease, and ventricular tachycardia were independent factors of a higher risk of TLE-related in-hospital complications. Multivariable analysis of the patients discharged from the hospital after the TLE procedure showed that TLE-related complications, a history of heart failure, and older age independently affected 12-month mortality. CONCLUSIONS: The presence of TLE-related in-hospital complications increased 12-month mortality.

Oleanolic and ursolic acids influence affect the expression of the cysteine regulon and the stress response in Escherichia coli.

The pentacyclic triterpenoids, oleanolic, and ursolic acids, affect peptidoglycan metabolism, altering bacterial morphology, and inhibit the growth and survival of several bacterial species, including pathogenic ones. We investigated the effect of subinhibitory concentrations of these compounds on the expression of three operons from the E. coli cysteine regulon, cysPTWA, cysJIH, and cysB, by using transcriptional fusions with the lacZ reporter gene. An inhibitory effect on ß-galactosidase expression directed by all three chromosomal fusions was observed with both compounds. In addition, oleanolic acid, but not ursolic acid, caused a weak increase in DnaK synthesis, suggesting moderate ability of inducing heat-shock response.

New antibacterial therapeutics and strategies.

Studies on new antibacterial therapeutics and strategies are currently being conducted in many microbiological, pharmaceutical and biochemical laboratories. The antibacterial activity of plant-derived compounds as well as silver and gold nanoparticles is the subject of this minireview. The application of photodynamic therapy is also discussed.

Radiation therapy in patients with cardiac implantable electronic devices.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) treated with radiation therapy (RT) as an oncological treatment is expected to increase. AIMS: The aim of the study was to assess whether cancer treatment with radiation therapy is associated with any device dysfunctions and device­related threats in patients with CIEDs. METHODS: The risk of all patients with CIEDs undergoing RT was assessed according to guidelines. Device interrogations were performed before the first and after the last RT session. In patients at high risk and/or with an implantable cardioverter­defibrillator or cardiac resynchronization therapy with defibrillator (CRT­D), all sessions were supervised by a cardiologist, and device interrogations were performed before and after every single RT session. Device parameters and events were monitored during thewhole treatment. RESULTS: The study included 157 patients with CIEDs who had palliative (n = 71) or radical (n = 86) RT. Pacemakers were implanted in 113 patients, implantable cardioverter­defibrillators in 36, and CRT­D in 8. During the 2396 RT sessions (median [interquartile range], 5 [5-28] per patient) with cumulative dose up to 78 Gy per patient for the whole RT treatment and maximum energy beam up to 20 MV, 2 events potentially related to radiation were recorded. CONCLUSIONS: Radiation therapy in patients with CIEDs is not associated with substantial risk to the patients assuming the patients' management follows current guidelines.

Oleanolic acid and ursolic acid affect peptidoglycan metabolism in Listeria monocytogenes.

The plant pentacyclic triterpenoids, oleanolic and ursolic acids, inhibit the growth and survival of many bacteria, particularly Gram-positive species, including pathogenic ones. The effect of these compounds on the facultative human pathogen Listeria monocytogenes was examined. Both acids affected cell morphology and enhanced autolysis of the bacterial cells. Autolysis of isolated cell walls was inhibited by oleanolic acid, but the inhibitory activity of ursolic acid was less pronounced. Both compounds inhibited peptidoglycan turnover and quantitatively affected the profile of muropeptides obtained after digestion of peptidoglycan with mutanolysin. These results suggest that peptidoglycan metabolism is a cellular target of oleanolic and ursolic acids.

Impaired Brain Energy Metabolism: Involvement in Depression and Hypothyroidism.

Although hypothyroidism appears to be an important factor in the pathogenesis of depression, the impact of thyroid hormones on the bioenergetics of the adult brain is still poorly known. Since metabolic changes are reported to be a key player in the manifestation of depressive disorder, we investigated whether there are differences in selected metabolic markers in the frontal cortex and hippocampus of Wistar Kyoto rats (WKY; an animal model of depression) compared to those of control Wistar rats and whether the induction of hypothyroidism by propylthiouracil (PTU) elicits similar effects in these animals or intensifies some parameters in the WKY rats. In our study, we used WKY rats as a model of depression since this strain exhibits lower levels of monoamines in the brain than control rats and exhibits behavioral and hormonal alterations resembling those of depression, including increased reactivity to stress. The findings indicate a decrease in glycolysis intensity in both brain structures in the WKY rats as well as in both strains under hypothyroidism conditions. Furthermore, hypothyroidism disrupted the connection between glycolysis and the Krebs cycle in the frontal cortex and hippocampus in the depression model used in this study. Decreased thyroid hormone action was also shown to attenuate oxidative phosphorylation, and this change was greater in the WKY rats. Our results suggest that both the depression and hypothyroidism models are characterized by similar impairments in brain energy metabolism and mitochondrial function and, additionally, that the co-occurrence of hypothyroidism and depression may exacerbate some of the metabolic changes observed in depression.

Brain Metabolic Alterations in Rats Showing Depression-Like and Obesity Phenotypes.

Current data suggest an important role of brain metabolic disturbances in the pathogenesis of depression and obesity, diseases that frequently co-occur. Our aim was to determine whether there are changes in markers characterizing glucose metabolism in prenatal stress (PS; animal model of depression), in rats fed a high-fat diet (HFD), and especially in the model of depression and obesity co-occurrence. The changes in glucose-6-phosphate, glycogen, glucose transporters (GLUT1, GLUT4), glucagon-like peptide-1 receptor (GLP-1R), and mitochondrial complexes levels in the frontal cortex and/or hippocampus were observed. In the case of the coexistence of depression and obesity, the most important changes were (1) the decrease in the membrane form of GLUT4, which may suggest weaker insulin action in the frontal cortex, and (2) the diminished GLP-1R, which could cause neurodegenerative changes in the hippocampus. However, presented results suggested that HFD weakened the PS effect of uncoupling oxidative phosphorylation in the frontal cortex.

Multicentre early experience with totally subcutaneous cardioverter-defibrillators in Poland.

INTRODUCTION: Implantable cardioverter-defibrillators (ICD) have a strong position in the prevention of sudden death. Nowadays, the most commonly used high-energy cardiac devices are transvenous ICDs. A new technology of totally subcutaneous ICDs (S-ICD) was invented and recently introduced into clinical practice in order to reduce lead-related complications of conventional ICDs. The aim of this paper is to present early experience with this new technology implemented in a few centres in Poland. MATERIAL AND METHODS: Medical records of patients who had S-ICD-related interventions in Poland were retrospectively analysed. RESULTS: During the first year of S-ICD introduction into the Polish health system 18 patients underwent surgery connected with S-ICDs. Majority of them (17 patients) were implanted de novo. In one patient surgical revision of a device implanted abroad was performed. Most of patients (78%) had S-ICDs implanted for secondary prevention. Inability of transvenous system implantation due to venous access obstruction or high risk of infection related with transvenous leads accounted for 83% of indications for S-ICD. Only in three patients were S-ICDs implanted due to young age and active mode of life. The implantations of S-ICDs were performed without important early or late complications. During follow-up one patient had episodes of ventricular arrhythmia successfully terminated with high-energy shocks. One patient died due to progression of heart failure. CONCLUSIONS: S-ICD implantation procedure has been successfully and safely introduced in Polish clinical routine. Nevertheless, despite clear indications in recent ESC guidelines, this therapy is not directly reimbursed in Poland and needs individual application for refund.

Inflammatory Consequences of Maternal Diabetes on the Offspring Brain: a Hippocampal Organotypic Culture Study.

Gestational diabetes is a disorder associated with abnormal chronic inflammation that poses a risk to the developing fetus. We investigated the effects of experimentally induced diabetes (streptozotocin model) in Wistar female rats on the inflammatory status of the hippocampi of their offspring. Additionally, the impact of antidiabetic drugs (metformin and glyburide) on inflammatory processes was evaluated. Organotypic hippocampal cultures (OHCs) were prepared from the brains of the 7-day-old rat offspring of control and diabetic mother rats. On the 7th day in vitro, the cultures were pretreated with metformin (3 µM) or glyburide (1 µM) and then stimulated for 24 h with lipopolysaccharide (LPS, 1 µg/ml). The OHCs obtained from the offspring of diabetic mothers were characterized by the increased mortality of cells and an enhanced susceptibility to damage caused by LPS. Although we showed that LPS stimulated the secretion of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) in the control and diabetic cultures, the levels of IL-1ß and IL-6 in the OHC medium obtained from the offspring of diabetic mothers were more pronounced. In the diabetic cultures, enhanced levels of TLR-4 and the overactivation of the NLRP3 inflammasome were demonstrated. Metformin and glyburide pretreatment normalized the LPS-induced IL-1ß secretion in the control and diabetic cultures. Furthermore, glyburide diminished both: LPS-induced IL-6 and TNF-α secretion in the control and diabetic cultures and increased NF-κB p65 subunit phosphorylation. Glyburide also diminished the levels of the NLRP3 subunit and caspase-1, but only in the diabetic cultures. The results showed that maternal diabetes affected inflammatory processes in the offspring brain and increased hippocampal sensitivity to the LPS-induced inflammatory response. The use of antidiabetic agents, especially glyburide, had a beneficial impact on the changes caused by maternal diabetes.