Marta Michalska

Takotsubo cardiomyopathy — The current state of knowledge

Takotsubo cardiomyopathy is defined as acute chest pain during stressful incidents which is associated with ST-segment abnormalities and/or increased serum troponin levels. There is also regressive systolic dysfunction which is usually localized in the apical and medial left ventricles but there are no significant coronary artery lesions. The ventricular asynergy is also described in the right ventricle but is less common. Almost all the patients are women. The onset of this disease is typically triggered by an acute emotional or stress event or by an accumulation of trivial and repetitive stresses. The etiology of this syndrome remains unclear. Myocardial ischemia and reperfusion due to microvascular spasm, aborted myocardial infarction and related no-reflow phenomenon have been proposed as inducers of Takotsubo cardiomyopathy. The temporal relationship between the stressful event and the triggering of the clinical syndrome as well as the report of elevated catecholamine plasma levels during the acute phase suggest a possible involvement of the sympathetic nervous system. A smaller left ventricular size and hormonal disturbances in women may also play a role.

What should be the optimal levels of blood pressure: does the J-curve phenomenon really exist?

Introduction: The blood pressure (BP) J-curve debate has lasted for over 30 years and we still cannot definitively answer all the questions. However, recent studies suggest that BP should be reduced carefully in patients with hypertension and coronary artery disease. BP should not fall below 110 – 115/70 – 75 mmHg, because this may be associated with more cardiovascular events. Areas covered: A retrospective analysis of the INVEST Trial and the results of the BP arm of the ACCORD Trial shows that care is needed in patients with hypertension and diabetes. Although the ACCORD BP Trial suggests important benefits connected with the significant reduction of stroke in patients being treated intensively, it also shows the lack of advantage of such therapy on each main and other additional endpoints. The ACCORD Trial also confirmed the increased risk of adverse events that might appear when intensive treatment was used in this group of patients. Expert opinion: Most available studies were observational and randomized trials (BBB, HOT, ACCORD BP), do not have or have lost their statistical power and were inconclusive. Further studies are therefore needed to provide definitive conclusions on the subject. In the meantime, it seems that in high-risk patients with hypertension, it is necessary to carefully select those who might suffer adverse events and those who may benefit from intensive BP lowering.

Influence of block of NF-kappa B signaling pathway on oxidative stress in the liver homogenates.

The aim of the present study was to assess whether BAY 11-7082, a nuclear factor-kappaB (NF-κB) inhibitor, influences the level of reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and NF-κB related signaling pathways in the liver. The animals were divided into 4 groups: I: saline; II: saline + endothelin-1 (ET-1) (1.25 μg/kg b.w., i.v.); III: saline + ET-1 (12.5 μg/kg b.w., i.v.); and IV: BAY 11-7082 (10 mg/kg b.w., i.v.) + ET-1 (12.5 μg/kg b.w., i.v.). Injection of ET-1 alone at a dose of 12.5 μg/kg b.w. showed a significant (P < 0.001) increase in thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) level and decrease (P < 0.01) in GSH level (vs. control). ET-1 administration slightly downregulated gene expression of p65 of NF-κB but potently and in a dose-dependent way downregulated p21-cip gene expression in the liver. BAY 11-7082 significantly decreased TBARS (P < 0.001), H2O2 (P < 0.01) and improved the redox status (P < 0.05), compared to ET-1 group. The concentration of TNF-α was increased in the presence of ET-1 (P < 0.05), while BAY 11-7082 decreased TNF-α concentration (P < 0.01). Inhibition of IkBα before ET-1 administration downregulated gene expression of p21-cip but had no effect on p65.

Influence of NADPH oxidase inhibition on oxidative stress parameters in rat hearts

BACKGROUND The aim of this study was to assess whether apocynin, an nicotinamide adenine dinucleotide phosphate (NADPH) oxidase blocker, influences lipid peroxidation TBARS, hydrogen peroxide (H2O2) content, protein level, heart edema, tumor necrosis factor α (TNF-α) concentration or the glutathione redox system in heart homogenates obtained from endothelin 1 (ET-1)-induced oxidative stress rats. METHODS Experiments were carried out on adult male Wistar-Kyoto rats. The animals were divided into 4 groups: Group I: saline-treated control; Group II: saline followed by ET-1 (3 μg/kg b.w., iv); Group III: apocynin (5 mg/kg b.w., iv) administered half an hour before saline; Group IV: apocynin (5 mg/kg b.w., iv) administered half an hour before ET-1 (3 μg/kg b.w., iv). RESULTS Injection of ET-1 alone showed a significant (p < 0.001) increase in thiobarbituric acid reactive substances (TBARS) and the hydrogen peroxide level (p < 0.01) vs. control, as well as a decrease (p < 0.001) in the GSH level. Apocynin significantly decreased TBARS (p < 0.001) and H2O2 (p < 0.05) level (vs. control) as well as improved protein level (p < 0.001) in the heart. Apocynin also prevented ET-1-induced heart edema (p < 0.05). The presence of ET-1 increased the concentration of TNF-α (p < 0.05) while apocynin decreased it (p < 0.05). Our results indicate that ET-1 may induce oxidative stress in heart tissue by reducing the GSH/GSSG ratio, stimulating lipid peroxidation and increasing TNF-α concentration. Apocynin diminished these measures of oxidative stress and TNF-α. CONCLUSION ET-1-induced formation of ROS in the heart is at least partially regulated via NADPH oxidase.

The knowledge and awareness of hypertension among patients with hypertension in central Poland: a pilot registry.

We assessed the differences in the knowledge and level of awareness of hypertension among patients with hypertension from Central Poland; 248 (57.6% females) patients diagnosed with hypertension completed a questionnaire. Most (79%) of the patients were unaware of the optimal blood pressure (BP) range. The elderly patients did not know the symptoms of hypertension (23.7%), were not willing to make lifestyle changes (57%-65%), and had a poor awareness of hypertension therapy in the absence of symptoms (28.7%). Poor BP control occurred mainly in rural residents (10.7%) and in people with higher education (39.3%). Untreated patients with hypertension did not know the symptoms of hypertension (29.2%), rarely measured BP (37.5%), but were more likely to engage in regular physical activity (70.8%). Efforts should be made to improve knowledge of hypertension, especially among the rural population, the elderly patients, those with a low-education level, and in young males who had the highest BP.

The effect of cadmium on the coagulation and fibrinolytic system in women with uterine endometrial cancer and myoma

ObjectivesCadmium (Cd) is a persistent and widespread environmental pollutant, which may constitute a potential risk factor for hormone-dependent tumors such as endometrial cancer. The vascular endothelium is an important target of cadmium toxicity, which may interfere with the coagulation cascade and fibrinolytic system. The aim of this research was to investigate whether in female patients with uterine endometrial cancer or myoma in comparison to healthy women, the concentration of cadmium in blood affects the process of coagulation and fibrinolysis.Materials and MethodsThe study group comprised 91 women: 35 healthy (A-control), 39 with uterine myoma (B) and 17 with endometrial cancer (C), in which blood cadmium concentrations (BCd), coagulation and selected fibrinolysis parameters in plasma were assayed.ResultsIn the women with myoma and especially in those with endometrial cancer disturbances in coagulation and fibrinolysis were detected when compared to the healthy women. In the group of women with endometrial cancer significant changes in prothrombin index, levels of fibrinogen, fibrin D-dimer and t-PA were observed. Whereas, in the patients with myoma significant changes in prothrombin time, index of vWillebrand Factor and fibrin D-dimer level were noted. Mean BCd concentrations in subsequent groups were as follows: B — 0.91±0.81; C — 0.78±0.45 μg Cd/l and did not differ significantly in comparison with the control group (0.86±0.35 μg Cd/l). However, in each study group smokers had approximately twice as high BCd as non-smokers. Studies also showed significant associations between BCd and fibrinogen level and thrombin time among the women with myoma and endometrial cancer, as well as in healthy women. Moreover, thrombin time significantly correlated with fibrinogen level in the women studied.ConclusionsIn the patients with myoma and especially in these with endometrial cancer disturbances in coagulation and fibrinolysis parameters leading to hypercoagulability were detected. Exposure to cadmium can be one of the factors inducing these changes.

Evaluation of Microcrystalline Chitosan and Fibrin Membranes as Platelet-Derived Growth Factor-BB Carriers with Amoxicillin

The aim of this study was to describe the mechanical and sorption features of homogeneous and composite membranes which consist of microcrystalline chitosan (MCCh) and fibrin (Fb) in various proportions as well as the in vitro kinetics of platelet-derived growth factor-BB (PDGF-BB) released from ten types of membranes in the presence or absence of amoxicillin (Am). The films were characterized by Fourier transform infrared (FTIR) spectroscopy, mechanical tests: breaking strength (Bs) and elongation at break (Eb), as well as SEM images, and swelling study. The influence of the form of samples (dry or wet) on Young’s modulus (E) was also examined. The homogeneous MCCh (M1) and composite M3 and M4 (MCCh : Fb = 2 : 1 and 1 : 1) membranes were characterized by good sorption properties and higher mechanical strength, when compared with Fb (M2) membrane. Connecting MCCh with Fb decreases release of PDGF-BB and increases release of Am. The most efficient release of PDGF-BB was observed in the case of M4 (the optimum MCCh : Fb ratio was 1 : 1) membrane. It was found that the degree of PDGF-BB release from the membrane is influenced by the physicochemical and mechanical characteristics of the films and by its affinity to growth factor PDGF-BB.

Can we extrapolate the outcomes of in vitro studies on murine endothelium to studies of human platelet-endothelium interactions? A technical note

Introduction Interactions between vascular endothelium and blood platelets play a crucial role in cardiovascular diseases. Ex vitro models which use endothelial cells and platelets were the essential tools to investigate these interactions and their impact on haemostasis. The impaired interplay between vascular endothelium, blood platelets and leukocytes is believed to contribute to the development of cardiovascular disease. In this study we compared the ability of human (HUVECs) and murine (HECa10) endothelial cells to inhibit human platelet function and reactivity under in vitro conditions. Material and methods The aliquots of platelet-rich plasma obtained from 20 healthy donors were incubated with murine endothelial cell line HECa10 or human umbilical vein endothelial cells (HUVECs) (10 min, 37°C) prior to agonizing platelets with 5 µM ADP and monitoring platelet reactivity for 10 min using optical aggregation. Results Significant reduction in ADP-induced platelet aggregation in the presence of endothelial cell cultures remained independent of cell count. HUVECs appeared much more effective in the inhibition of platelet aggregation compared to HECa10 (35.2 ±2.3 AU vs. 43.7 ±2.0 AU, p= 0.025). Conclusions HECa10 cells have much lower potential to inhibit platelet aggregation than HUVECs. This implies that these two cell lines may not be freely used interchangeably in in vitro experiments. These findings clearly indicate that the outcomes of in vitro studies performed with murine EC lines cannot be unreservedly extrapolated to human platelet-endothelium interactions.

Effect of methylmercuric chloride (MMC) on fibrin polymerization.

Methylmercuric chloride (MMC) in concentrations 0.1–10μM reduces the amount of fibrinopeptides released from thrombinactivated human fibrinogen. However, the fibrin clot formation is not discriminated and the turbidity of the fibrin gel is even augmented. MMC does not cause such changes in the process of repolymerization of fibrin monomers. The addition of fibrinopeptides to the fibrin monomers results in a similar increase of turbidity of the repolymerizing sample in the presence of MMC as in the case of fibrinogen clotting. These experiments indicate that MMC modifies the structure of fibrin in the presence of fibrinopeptides.

The effect of hydrazine derivatives of 3-formylchromones on angiogenic basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanoma cell line WM-115

The hydrazine derivatives of benzopyrones remain an unexplored group of chemical compounds. This preliminary study investigates the influence of A-5, CH-3 and K-2 derivatives at concentrations of 1, 10, 100 nM and 1 μM on selected biochemical factors of a melanoma cell line WM-115, with regard to their potential angiogenic properties. The studied compounds were found to influence cell proliferation, as well as total protein, bFGF and FGFR1 concentration.