Józefa Dąbek

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB): a new potential therapeutic target in atherosclerosis?

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a crucial transcription factor that participates in a number of physiological and pathological conditions, including immune response, apoptosis, carcinogenesis and inflammatory processes. It is involved in the rapid response to various stimuli such as viral and bacterial infections, shear stress, oxidant stress and a number of cytokines. In the pathology of atherosclerosis NF-κB is essential to the cross-talk between cytokines, adhesion molecules and growth factors, leading to atherosclerotic plaque formation, growth and eventual rupture. The intent of this paper is to gather and summarize information on the role of NF-κB in the pathology of atherosclerosis. Additionally, pharmacological intervention in the signaling of NF-κB is addressed along with the potential benefits and disadvantages of NF-κB modulating treatment.

Oligonucleotide Microarray Analysis of Genes Regulating Apoptosis in Chronically Ischemic and Postinfarction Myocardium

The pathology of cardiomyocyte death during and after myocardial infarction involves both necrosis and apoptosis. Although both mechanisms lead to cell death, participation of apoptosis in this process carries the potential of developing therapies influencing at least part of the population of dying cells. Therefore the aim of this study was to determine (using oligonucleotide microarrays) expression profiles of apoptosis-regulating genes in postinfarction myocardium, comparing chronically ischemic and healthy heart muscle. Tissue samples were obtained during elective surgery from the right cardiac auricles of three patients. The expression of 141 genes involved in fibrosis was assessed using the Affymetrix HG_U133A microarray. The patients’ transcriptomes were compared using hierarchical clusterization. Differentiating genes were determined using regression analysis and Bland–Altman graph analysis. Hierarchical clusterization demonstrated that the profile of gene expression in postinfarction myocardium was different from that in the remaining specimens. Further statistical analysis showed two important differentiating genes: FOXO3A (underexpressed in post-MI sample) and CFLAR (overexpressed in post-MI sample). The expression of apoptosis-regulating genes is significantly different in post-MI myocardium from chronically ischemic and a nonischemic myocardium. Our results suggest that CFLAR is important in the induction of apoptosis in postinfarction cardiac tissue.

Expression analysis of intercellular adhesion molecule-2 (ICAM-2) in the context of classical cardiovascular risk factors in acute coronary syndrome patients

Introduction Cardiopulmonary diseases are the most common cause of hospitalization and death. Often the basic problem is endothelial dysfunction leading to elevated expression of adhesion proteins as well as increased adhesion and aggregation of blood cells. The goal of the study was to assess expression level of intercellular adhesive molecule-2 (ICAM-2) in patients with acute coronary syndrome (ACS). Material and methods The obtained data were analysed in the context of the occurrence of classical cardiovascular risk factors. The two studied groups consisted of 60 ACS patients and 20 healthy individuals who both were qualified based on electrocardiography (ECG), transthoracic echocardiography and biochemical tests. The ACS patients additionally had coronary angiography performed. The number of ICAM-2 gene mRNA molecules was evaluated on the basis of QRT-PCR reaction kinetics. To compare the results the Mann-Whitney U test was used. Results were judged statistically significant if p < 0.05. Results Analysis of the results showed a significantly higher number of ICAM-2 gene mRNA copies in ACS patients compared to healthy subjects (140920 ±105207 and 15023 ±14325, respectively). Furthermore, our results indicate a correlation between obesity (p = 0.012) and positive burdening family history (p = 0.041) and increased ICAM-2 levels in patients with ACS. Conclusions Increased ICAM-2 gene expression in ACS patients is probably symptomatic of endothelium dysfunction and may be responsible for intensified adhesion and aggregation processes as well as for appearance of acute coronary syndrome. These results indicate a correlation between obesity and burdening family history on the one hand, and increased ICAM-2 levels in patients with ACS, on the other.

DNA microarray study of genes differentiating acute myocardial infarction patients from healthy persons

Objective: Using oligonucleotide microarrays HG-U133A, we here studied the expression levels of genes that could differentiate between patients with myocardial infarction (MI) from healthy subjects, as well as to select among such genes those that seem crucial for manifestation of cardiovascular diseases. Materials and methods: The microarray study was conducted using material derived from blood samples collected in 17 individuals. Results: Analysis of gene expression data from 17 microarrays allowed identification of 28 genes strongly differentiating the examined groups. Conclusion: The differentiating genes that we tracked down indicate possible linkage with atherosclerotis and could be a prognostic marker for development of cardiovascular diseases.

Effects of standard treatment on the dynamics of matrix metalloproteinases gene expression in patients with acute coronary syndromes

Inflammation plays a critical role in the pathology of acute coronary syndrome (ACS). Matrix metalloproteinases (MMP)--proteolytic enzymes participating in plaque destabilization--are the crucial effectors of proinflammatory mechanisms leading to plaque rupture. Numerous reports have confirmed the significance of these factors both in circulating blood and locally in the plaque. There is, however, a lack of information on the molecular mechanisms leading to these disturbances, and the effect of standard treatment for ACS on these processes. The aim of the study was to assess the gene expression of MMP-2, -9 and TIMP-2, and the effect of standard treatment on the expression of the studied genes. The study was conducted in 32 patients with ACS and 15 healthy subjects (control group). Monocytes were isolated using Rosette-Sep kits. Gene expression of MMP-2, MMP-9 and TIMP-2 was evaluated on days 1 and 5 in the studied group and once in controls. Total mRNA was extracted from monocytes and the number of mRNA copies was assessed by QRT-PCR. Monocytes of ACS patients present with significantly higher gene expression of MMP-2, -9 and TIMP-2 compared to healthy controls (0.0915 ± 0.037 vs. 0.001 ± 0.0002, p < 0.01; 0.81 ± 0.279 vs. 0.10 ± 0.057, p < 0.05; 0.84 ± 0.140 vs. 0.42 ± 0.126, p < 0.05, respectively). After the 5-day standard treatment, a significant decrease in MMP-2 gene expression was observed. Other studied genes did not show relevant changes during the observation period. No significant correlation was found between classical atherosclerosis risk factors and the expression of the studied genes. Monocytes of ACS patients significantly overexpressed MMP-2, MMP-9 and TIMP-2. Five days of standard treatment resulted in downregulation of the MMP-2 gene. MMP gene overexpression appears to be an independent factor concerning the pathogenesis of ACS.

Female and male orbit asymmetry: Digital analysis

BACKGROUND Standard anthropometric methods applied to measurements of the skull differentials are laden with mistakes stemming from the way the measuring devices are built and from a lack of experience on the part of the researchers. To increase objectivity, digital imaging measurements via computer systems were introduced. OBJECTIVES The aim of this research was to assess the asymmetry of the male and female orbit with the application of the new graphic methods: raster graphics and vector graphics. MATERIAL AND METHODS The examination was conducted on 184 well-preserved skulls. The photos were taken by a digital camera with high definition. Orbit asymmetry was examined by determining the distance between the centers of gravity of both orbits and the frontal median line d1 and d2. Then angles α and β were appointed. They are defined as angles between the line that runs through craniometrical points mf and ek on the right side (angle α) and on the left side (angle β), and the frontal median line at their crossing point. Distances r2 and r1, which are allocated points between the frontal median lines (LPP), were also set. RESULTS Angles α and β were also analyzed while comparing the skulls of both genders. Statistically significant differences were only observed in male skulls. However, differences for both genders were noted in parameters d1 and d2. No statistically significant differences were discovered between men and women for parameters r1 and r2. The groups of women and men were merged, being treated as a population; which resulted in the conclusion that there are no statistically significant differences between these parameters. CONCLUSIONS The skulls asymmetry connected to gender and the asymmetry of the right and left sides of examined craniums can be used in criminal examinations as well as in facial reconstructive surgeries.

Assessment of risk factors for mortality in patients with cardiovascular disease and a history of treatment for malignancy

BACKGROUND Patients with advanced cancer after radio- and/or chemotherapy are increasingly commonly hospitalised in cardiology units due to coexisting cardiovascular diseases (CVD). A rational assessment of mortality risk is an important part of patient preparation for invasive cardiac procedures. One disadvantage of cardiac risk scores is the fact that malignancies are not taken into account. At present, accurate estimation of life expectancy is possible in up to 20% of patients with an advanced malignancy. AIM To evaluate the effect of selected clinical parameters on survival of patients with CVD and coexisting lung or breast cancer after radio- and/or chemotherapy. An additional aim was to identify patients with a high probability of surviving a year in a good general clinical condition. METHODS The study group involved 326 subjects with established CVD and lung cancer (small-cell or non-small-cell) or breast cancer who were selected from the group of 7818 patients receiving palliative care in the Palium hospice in Czestochowa, Poland, in 2008-2012. The obtained data were collected in a database and subjected to a statistical analysis. RESULTS The strongest factors associated with an increased risk of death among patients with CVD and coexisting advanced lung or breast cancer after chemo- and/or radiotherapy were the type and stage of malignancy, functional status according to the ECOG classification, and the presence of cachexia. Other factors that had a significant effect on survival included higher severity of heart failure symptoms as evaluated by the New York Heart Association class, decreased left ventricular ejection fraction, presence of ischaemic heart disease, chronic obstructive pulmonary disease, fasting hyperglycaemia, and the severity of fatigue, nausea, and pain. When the effects of drug treatment on survival were analysed, significantly increased survival was observed in patients treated with angiotensin-converting enzyme inhibitors while diuretic and glucocorticosteroid use was associated with decreased survival. Among the evaluated groups of patients with CVD and advanced malignancy after radio- and/or chemotherapy, the highest probability of surviving a year in a relatively good general clinical condition was noted in patients with stage 3 breast cancer without cachexia, ischaemic heart disease and persistent somatic symptoms who were treated with tamoxifen, angiotensin-converting enzyme inhibitors and megestrol acetate. CONCLUSIONS This is the first study that evaluated the combined effect of oncological and cardiovascular risk factors on survival of patients with CVD and coexisting cancer after radio- and/or chemotherapy treatment. When the three groups of cancer patients with different prognosis were compared, the study revealed varying effects of each factor depending on the underlying malignancy. The analysis confirmed the significance of the cumulative risk. The present study showed that malignancy-related prognostic factors are important in the context of cardiac evaluation and treatment of cancer patients. It also showed that further research is needed to clarify these issues.

A patient with abnormalities of the coronary arteries and non-compaction of the left ventricular myocardium resulting in ischaemic heart disease symptoms

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy that results from unsettled embryogenesis of myocardium. It is morphologically characterised by the presence of non-compacted, this is hypertrabeculated, myocardium of the left ventricle with deep endocardial recesses. The clinical spectrum of symptoms is very wide - from asymptomatic patients through the cases of heart failure to the patients requiring heart transplantation. The diagnosis is most frequently based on the echocardiography. LVNC is often coexisted with other heart defects and coronary artery abnormalities. We described a case of a 58-year-old man with LVNC and coronary artery anomalies.

Orbital Opening Shape and Its Alphanumerical Classification.

BACKGROUND Orbit is the one of the most complicated areas of the facial part of cranium. The anthropological analysis of the orbits comprises basic measurement characterizing their shape: width and height. Classic anthropometric methods used to measure the skull variability are burdened with mistakes resulting from construction of measuring devices as well as from researchers experience. OBJECTIVES The purpose of our research was to introduce a metric classification of the orbital opening. MATERIAL AND METHODS The study was carried out on 184 skulls. In our study we suggest introducing a classification of the orbital opening shape by calculating a functional for the 15 categories of the orbit shape. Shape categories have been arranged following the increasing value of the functionals. Each shape category of the orbital opening, according to the Piaseckis descriptive classification, was assigned a letter from the alphabet. RESULTS We have observed a greater number of symmetrical skulls in the female group (29.11%) than in the male (23.81%). In both groups the symmetry type AA was the most frequent, it corresponds to the value of functional comprised in the interval from 0 to 1,30. According to the Piaseckis descriptive classification it was the oval elongated type. CONCLUSIONS Our alphanumerical classification based on the value of functional and on the orbit outline assigned to the value is an objective and useful method of the orbital opening shape analysis.

Patients with infective endocarditis: Five-year observation from a single reference center

BACKGROUND Infective endocarditis (IE) is a serious and, if untreated, usually fatal disease. Diagnosing IE is often considered to be one of the most difficult medical conditions because of the heterogeneous and ambiguous clinical presentation. OBJECTIVES The purpose of this study was to investigate diagnostic and therapeutic management in a non-selected group of patients with IE. MATERIAL AND METHODS A total of 45 patients consecutively admitted to the Department of Cardiology, Medical University of Silesia in Katowice (mean age 53.6 ±18 years; 13 females) with IE between 2009 and 2013 were evaluated. Echocardiography, blood cultures and laboratory tests were performed on every patient upon admission. An analysis of the diagnostic and therapeutic management was performed. RESULTS Most frequent predisposing factors were: a history of heart valve replacement and/or repair (40%), dental caries (17.8%) and bicuspid aortic valve (17.8%). The majority of patients were admitted from another hospital (91.1%). Fever (92%) and symptoms of heart failure (80%) were the most common manifestations. Abnormalities in ECG occured in 91.2% of patients. Echocardiography was highly sensitive (>90%) in detecting endocardial changes. Staphylococcal etiology was the most common (33.3%). Surgery procedures were necessary in 62.2% of patients. Arrhythmias (91.1%) and acute heart failure (57.8%) were the most commonly observed complications, although 24.4% of subjects had neurological disorders. The patients studied were burdened with a number of factors predisposing to IE. CONCLUSIONS The diagnosis of IE can be a difficult challenge. Particular attention should be paid to the care of oral hygiene and treatment of dental diseases in order to reduce the risk of IE developing.