Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Antibodies crossreacting with human TNF-alfa receptor induced in the patients with coronary heart disease by Helicobacter pylori CagA positive strains

Abstract Introduction Coronary heart disease (CHD) is associated with inflammation and atherosclerosis. The hypothesis of autoimmune origin of CHD has been suggested. Chronic infection with gastric pathogen Helicobacter pylori may induce antibodies, potentially autoreactive, due to molecular mimicry between H. pylori cytotoxin associated gene A (CagA) protein and tumor necrosis factor (TNF)-α receptor (TNFR). Purpose To evaluate presence of antibodies against synthetic c peptide (P1), which mimics the common sequence of TNFR and H. pylori CagA, in the sera of CHD patients and healthy donors (HD), uninfected or infected with H. pylori. Furthermore, guinea pigs (Caviae porcellus), sensitive to H. pylori infection, were used to confirm the induction of antibodies crossreacting with TNFR by this pathogen. Material and methods Serum samples from CHD patients infected with H. pylori CagA(+) strain (43) or H.pylori CagA(−) strain (12), and uninfected HD (16) without symptoms of gastritis or CHD were selected. Moreover, the serum samples from control (10) or H. pylori infected guinea pigs, 7, 28 and 60 days from inoculation were used (10, 20, 10, respectively). The H. pylori status in humans was confirmed by 13C urea breath testing and anti-H. pylori antibody production whereas in Cavia porcellus by histological examination of gastric tissue, detection of H. pylori antigens in stool as well as serum anti-H. pylori antibodies. The ELISA assay with the surface H. pylori antigens – glycine acid extract (GE), recombinant CagA (IRIS, Siena, Italy), synthetic P1 or P2 peptides (Lipopharm, Gdansk, Poland), with or without common CagA/TNFR sequence, respectively, were used for detection of antibodies. Complement activation by P1-anti-P1 IgG complexes was determined by complement fixation assay with sheep erythrocytes (SRBC) and anti-SRBC antibodies. Results :Anti-P1 IgG were detected only in CHD patients infected with H. pylori CagA(+) but not CagA(−) strain. Such antibodies were not detected in H. pylori uninfected HD. Anti-P1 IgG were found in the sera of Cavia porcellus infected with H. pylori, 7 and 28 but not 60 days from inoculation. This may suggest the clearance of such antibodies during the course of infection or their early deposition. The role of H. pylori in anti-P1 IgG induction was confirmed by deletion of such antibodies by absorption of sera, which were positive for anti-P1 IgG, with heat inactivated H. pylori. Anti-P1 IgG present in human and animal sera were biologically active. They formed the immune complexes (IC) with P1 in vitro, which were able to activate complement, suggesting a pro-inflammatory potential of such IC in vivo. Conclusions During H. pylori infection in CHD patients the CagA protein of this pathogen may induce antibodies cross reacting with TNFR. They can potentially increase the inflammatory response by IC dependent activation of complement or due to modulation of TNFR-driven cell signaling pathways. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Statutory Fund of University of Lodz, Poland </jats:sec

P4502Noninvasively assessed mitochondrial function estimated by skin fluorescence is abnormal in coronary artery disease

Abstract Mitochondrial NADH undergoes oxygenation to NAD+ and NADH molecules, activated by ultraviolet light, start to emit fluorescence at a wavelength 460nm. This phenomenon can be measured to non-invasively assess mitochondrial function in the forearm epidermis at rest, during transient ischaemia, and afterward reperfusion assuming that it reflects abnormal microvascular circulation. We hypothesized that flow-dependent skin fluorescence (FDSF) is abnormal in patients with coronary atherosclerosis. Methods Prototype device manufactured by Angionica (Poland) was used to quantify FDSF recorded in forearm before, during and after 100 s of brachial artery occlusion in 63 individuals (26 with coronary artery disease (CAD) and 37 healthy volunteers. The absolute value of baseline FDSF (BASE), maximum FDSF (MAX), minimal FDSF (MIN), percentage ischemic response (IR) and hyperemic response (HR) were measured. Age, lipid profile, fasting glucose, HbA1c, C-reactive protein (CRP), systolic and diastolic blood pressure, pulse wave velocity (PWV), augmentation index, time domain heart rate variability parameters (SDNN, rMSSD) and estimated apnea/hypopnea index -eAHI (Holter ECG based), BMI, intima-media thickness (IMT), left ventricle systolic and diastolic function were determined in all study participants to search for potential correlations with FDSF. Results Measurements were feasible in all study subjects and examination duration was 9±1min. Hyperemic response (HR) was significantly lower in patients with CAD vs controls: 10,4 vs. 14,36 vs 14,73 – p=0,025. Other parameters: BASE, MAX, MIN, and IR were not significantly different between groups (p&gt;0,05). In the entire group, HR was correlated with age (r=−0,23 p=0,037), and with total or LDL cholesterol (r=0,37 p=0,001 and r=0,36 p=0,001). Interestingly, HR was also positively correlated with SDNN (r=0,26 p=0,044) and rMSSD (r=0,29 p=0,026). Mode of FDSF examination Conclusion Abnormal mitochondrial function probably secondary to microcirculatory disorder is detectable by noninvasive skin fluorescence test as decreased hyperemic response in patients with coronary disease. Age and cholesterol concentration as well as autonomic balance Holter indices are correlated with hyperemic response. Acknowledgement/Funding POIR.01.01.01.0540/15-00 </jats:sec

March, September and December months with the greatest influence of atmospheric pressure on blood pressure in patients with hypertension

Abstract Objectives For a long time, science has searched for the relationship between weather and human health. Atmospheric pressure is the most objective weather factor because, regardless of whether the objects are outdoors or indoors, it affects all objects in the same way. In cardiology, we often look for factors that worsen blood pressure control. Could atmospheric pressure be one of them? The main objective of our research was to assess the relationship between atmospheric pressure and blood pressure in patients with treated hypertension in different months in the moderate climate of Central Poland. Material and methods The study group consisted of 4191 patients with arterial hypertension, divided into 2 near equal groups due to a lower or higher average value of atmospheric pressure when blood pressure was recorded. Blood pressure was monitored by a means of 24-h ABPM. Atmospheric pressure was recorded with the frequency of 1 measurement per minute using a meteorological station. The observations were conducted in the years 2009–2019. Comparisons between blood pressure values in the 2 groups were performed using the Mann-Whitney U test. Results We observed a significant difference in blood pressure recorded during the periods of lower and higher atmospheric pressure: for systolic blood pressure during the days of September (125.01±14.99 vs 120.14±12.83, p&amp;lt;0.001) and December (124.22±15.45 vs 127.50±14.35, p&amp;lt;0.05), for diastolic pressure during the days of March (72.24±10.92 vs 69.81±9.13, p&amp;lt;0.02) and for diastolic pressure during the nights of March (61.53±8.96 vs 59.58±9.17, p&amp;lt;0.04). Conclusions A significant inverse relationship between atmospheric pressure and blood pressure was observed; during March days and nights for diastolic blood pressure and during September and December days for systolic blood pressure. This finding may be important for the understanding of why during some months the pharmacological control of blood pressure is poor, and of the consequences of this fact. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): own resources </jats:sec

Detection of specific Helicobacter pylori DNA and antigens in stool samples in dyspeptic patients and healthy subjects

In this study stool samples from dyspeptic patients and healthy subjects were used for detection of specific Helicobacter pylori antigens and DNA by immunoenzymatic test (PPHpSA) and semi-nested PCR (ureA-PCR), respectively. The H. pylori status was estimated by invasive endoscopy-based rapid urease test and histology or noninvasive urea breath test (UBT), and by serology (ELISA, Western blot). The coincidence of IT pylori-negative invasive tests or UBT and negative antigen or DNA stool tests was very high (mean 95%). The PPHpSA results were found positive for 56% and ureA-PCR for 26% of individuals with H. pylori infection confirmed by invasive tests or UBT. The detection of specific H. pylori antigens and especially DNA in feces is not sufficient as a one-step diagnosis of H. pylori infection