Ilona Korzonek-Szlacheta

Triterpenes as potentially cytotoxic compounds.

Triterpenes are compounds of natural origin, which have numerously biological activities: anti-cancer properties, anti-inflammatory, anti-oxidative, anti-viral, anti-bacterial and anti-fungal. These substances can be isolated from plants, animals or fungi. Nowadays, when neoplasms are main cause of death, triterpenes can become an alternative method for treating cancer because of their cytotoxic properties and chemopreventive activities.

Relationship Between Plasma Pentraxin 3 Concentration and Platelet Indices in Patients With Stable Coronary Artery Disease

Few reports have analyzed the effect of pentraxin 3 (PTX3) on platelets and their activation. We explored the association between plasma PTX3 and platelet indices. Forty-nine patients with stable coronary artery disease (CAD) were enrolled. Based on median PTX3, the study population was divided into group 1 (n = 25; PTX3 ≤ 0.98 ng/mL) and group 2 (n = 24; PTX3 > 0.98 ng/mL). Platelet indices investigated included mean platelet volume (MPV), platelet distribution width (PDW), platelets and large cell ratio (P-LCR), MPV to platelet count ratio (MPV/PC), platelet to lymphocyte ratio (PLR), and MPV to lymphocyte ratio (MPVLR). Patients with lower PTX3 had a higher lymphocyte count. Platelet count was similar in both groups. Notwithstanding, patients with higher PTX3 concentrations had elevated MPV (8.3 vs 10.0 fL; P < .001) and PDW (9.4 vs 12.4 fL; P < .001). However, the MPV/PC ratio was similar in both groups. Thromboinflammatory biomarkers (PLR, MPVLR) were also elevated in group 2. Pentraxin 3showed a strong, positive correlation with MPV (r = .75, P < .01) and PDW (r = .80, P < .01), and weak to moderate correlation with MPVLR. In conclusion, PTX3 is associated with larger platelet size as assessed by platelet volume indices. There is a strong correlation between plasma PTX3 level and MPV and PDW.

Platelet Volume Measurements—EDTA, Citrate, or Both?

We appreciate the comments made by Dr Yildirim and colleagues. First, we agree that preanalytical factors play a key role in obtaining reliable results and that such errors can result in erroneous conclusions. Thus, all blood samples in our study were tested within 1 hour of collection. Second, we used ethylenediaminetetraacetic acid (EDTA) for whole blood anticoagulation. Some reports demonstrated that the mean platelet volume (MPV) increases with the use of EDTA due to platelet swelling, thus, suggesting the use of acid citrate as anticoagulant. However, most studies indicate that MPV can be measured accurately by both methods of anticoagulation—EDTA and citrate—if analysis is performed within 1 hour of sampling. Dastjerdi et al evaluated whether EDTAand citrate-based anticoagulated blood samples can be used interchangeably for MPV measurement. In the 61 patients, there was a close correlation between MPV as measured in EDTA and citrate, but MPV measured from EDTA samples was 0.66 fL (9%) greater than when collected in citrate. Both methods also showed a significant negative correlation between platelet count and MPV. The study indicates that MPV can be measured accurately by both methods of anticoagulation, EDTA and citrate, if the analysis is performed within 1 hour of sampling. Lance et al also demonstrated that platelets swell until 120 minutes in EDTA and until 60 minutes in citrate. So they suggest that optimal measuring time should not exceed 120 minutes. Interestingly, they demonstrated that the platelet count was most stable in EDTA. As to plateletcrit, it provides data regarding total platelet mass, whereas MPV and platelet larger cell ratio (P-LCR) are indicators of circulating larger platelets (>12 fL) and have also been used to monitor platelet activity. These are the reasons why we chose to study the associations of MPV and P-LCR with pentraxin 3 (PTX3) and C-reactive protein (CRP). Furthermore, there is paucity of data on the role of plateletcrit in stable coronary artery disease. Therefore, we did not record this variable in our study. Notwithstanding, the authors make an interesting point for future studies. Regarding correlation between CRP and platelet to lymphocyte ratio (PLR), and lack thereof between PTX3 and PLR, we speculate that different mechanisms underlie this phenomenon. One possibility might be the local nature of PTX3 actions in contrast to the systemic actions of CRP. However, we cannot exclude that our results are limited by a relatively small sample size.

Prognostic impact of multimorbidity in patients with type 2 diabetes and ST-elevation myocardial infarction

Introduction There is an increasing body of evidence on the clinical importance of multimorbidity, which is defined as the coexistence of two or more chronic conditions. Type 2 diabetes (T2DM) is one of the most frequent chronic conditions. Most adults with type 2 diabetes have at least 1 coexisting chronic condition and approximately 40% have 3 or more. Prior studies have suggested that cardiovascular (CVD) and non-CVD comorbid conditions yield worse outcomes in patients hospitalized with ST-elevation myocardial infarction (STEMI). It is unclear, however, the extent to which multimorbidity has a cumulative effect on long-term risk. Therefore we have set out to determine the prognostic value of multiple comorbidity on long-term outcomes in this population of patients. Methods A total of 277 patients with T2DM and STEMI undergoing primary percutaneous coronary intervention (PCI) were enrolled. Based on the number of comorbidities the study population was divided into two groups: group 1 (N=58) with ≤ 1 comorbidity and group 2 (N=219) with ≥ 2 comorbidities. Results Comorbid conditions were prevalent among study participants (Figure 1). The median number of comorbidities was three. 15.9% of patients had one comorbidity and 22.0%, 34.3%, and 22.7% of patients had two, three or at least four comorbid conditions respectively. A majority of patients had at least one CVD comorbidity (6.1% of patients had none), whereas 53.1% of patients did not have any non-CVD comorbidity. During hospitalization 3 out of 58 patients (5.2%) died in group 1 and 25 of 219 patients (11.4%) died in group 2. The number of comorbid conditions was not an independent predictor of in-hospital death. During 12-month follow-up, 5 of 58 patients (8.6%) and 42 of 219 patients (19.9%) died, respectively in group 1 and 2 (P=0.05). The number of comorbid conditions proved in ROC analysis that for 12-month mortality, the prognostic value was modest, but for 12-month acute coronary syndromes the prognostic value was good. Increase in the number of comorbid conditions by one was associated with a 15% increase in the relative risk of 12-month mortality and a 41% increase in the relative risk of 12-month acute coronary syndromes (ACS). Conclusions Comorbid conditions are highly prevalent among these groups of patients. Majority of patients have at least 2 other cardiovascular comorbidities and one or two non-cardiovascular comorbidities. In terms of long-term follow-up, multimorbidity was associated with worse outcomes. The risk of both long-term mortality and ACS increased with the increasing number of comorbidities. In summary, our findings highlight the importance of indentifying patients with multimorbidity. This, in turn, could allow for provision of better care to these high-risk and complex group of patients.

Chalcones Target the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Signaling Pathway for Cancer Chemoprevention

Abstract Chalcones belong to the flavonoids family and are natural compounds present in edible plants. The term chalcone was coined by Stanislaw Kostanecki and Josef Tambor. Chalcones exhibit a broad spectrum of biological activity and thus have attracted more and more attention due to their anticancer and chemopreventive effects. Chemoprevention is one of the most promising approaches for arresting many types of cancer cells or reversing the process of carcinogenesis. Preclinical and epidemiological studies have shown that chalcones can inhibit cancerogenesis at very early stages. The tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a protein that exists in soluble form or is expressed on the surface of immune effector cells. This ligand induces apoptosis in cancer cells while showing no toxicity for normal cells. Some cancer cells, however, are resistant to TRAIL-mediated cell death through a many survival mechanisms. Chalcones in combination with TRAIL can sensitize TRAIL-resistant cancer cells to apoptosis through different mechanisms in apoptotic pathway.

Effects of trimetazidine on interleukin-2 and interleukin-8 concentrations in patients with coronary artery disease

Trimetazidine (TMZ) exhibits metabolic and cardioprotective effects. The aim of this study was to assess the effects of TMZ on interleukin-2 (IL-2) and interleukin-8 (IL-8) serum concentrations in 156 patients with stable coronary artery disease. They underwent a treadmill exercise test (TET) before and after 3 months of TMZ treatment. IL-2 and IL-8 concentrations were determined before and after each TET. Before treatment, TET did not influence IL-2 concentrations, whereas IL-8 concentrations increased. TMZ treatment led to a decrease in IL-2 concentrations before TET, as well as it prevented the increase of IL-8 following the second TET. Obtained results confirmed the improvement in TET performance during TMZ treatment and they revealed a significant influence of TMZ on IL-2 and IL-8 concentrations both before and after TET. These changes may reflect potential anti-inflammatory effects of TMZ.

Płytki krwi — ogniwo łączące zakrzepicę ze stanem zapalnym

Glowną funkcją plytek jest ich udzial w procesach hemostazy. W ostatnich dwoch dekadach wzroslo znaczenie roli plytek krwi w stanach zapalnych oraz w chorobach nowotworowych. Po aktywacji plytki krwi wydzielają ponad 300 substancji z wewnątrzkomorkowych ziarnistości. Zawartośc ziarnistości gestych, miedzy innymi: adenozynodifosforan (ADP — adenosine diphosphate), serotonina, histamina, polifosforany, i ziarnistości α, miedzy innymi: fibrynogen, czynnik von Willebranda, czynniki krzepniecia, odgrywają wazną role w procesach hemostazy i krzepniecia, stanowiąc rowniez istotny czynnik powstawania przerzutow nowotworowych. Ziarnistości α zawierają wiele cytokin, mitogenow, czynnikow pro- i przeciwzapalnych oraz innych cząsteczek bioaktywnych, ktore są niezbednymi regulatorami w zlozonym środowisku tworzącej sie skrzepliny, przyczyniając sie do wielu procesow chorobowych — przede wszystkim tych związanych ze stanem zapalnym i reakcjami immunologicznymi organizmu. W niniejszej pracy poglądowej podsumowano obecne rozumienie funkcji plytek w procesach chorobowych.

Single nucleotide polymorphisms for genes encoding cytokines in the context of cardiac surgery. Part I: Heart transplantation.

Cardiovascular diseases remain the leading cause of death in Poland and other countries of the European Union. Patients with end-stage heart failure constitute a patient subgroup for whom the treatment of choice is heart transplantation. Despite advances in immunosuppressive therapy, acute or chronic graft rejection occurs in 20-30% of cases in the first six months after transplantation. The significance of the immune response and inflammation in graft rejection implies the important role of cytokines. Molecular markers are sought to facilitate risk assessment and improve patient care. At present, genetic tests are not used for this purpose, but studies aiming to rectify that have been conducted for years, including studies on single nucleotide polymorphisms of cytokine genes. This paper presents the results of research on the single nucleotide polymorphisms (SNPs) of the IL-2, IL-4, IL-6, IL-10, TGF-β1, PDGF, VEGF, and TNF-α genes in conjunction with heart transplantation. The analyzed data do not allow for reliable application of these genetic tests in clinical practice, but suggest that it is a promising direction which may improve the options of treatment individualization in the future.