Antal Tibold

Bio: Antal Tibold is an academic researcher from University of Pécs. The author has contributed to research in topics: Burnout & Aspirin. The author has an hindex of 8, co-authored 30 publications receiving 305 citations.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications.

Abstract: Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

Clinical importance of aspirin and clopidogrel resistance

Abstract: Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked “aspirin and/or clopidogrel resistance”, as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer.

Abstract: Background: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. Patients and Methods: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. Results: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). Conclusion: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy. Malignancies of the gastrointestinal tract are among the most frequent malignant diseases in Hungary (1). Cancer of the colorectal region is the second most frequent cause of death from malignant diseases (2). Traditional gastronomical habits which include fatty and dietary fiber deficient foods and the popularity of meats preserved by smoke explain the high prevalence of these diseases (3). In our present study we aim to examine the relationship between certain allelic polymorphisms and related cancer risk, and its influence on the survival of inflected patients. Our area of interest is in two allelic polymorphisms of glutathione-S-transferases, the GSTM1 and GSTT1 metabolizing enzymes. Glutathione-S-transferases (GSTs) are involved in the metabolism of endogenous and exogenous carcinogenic substances, such as environmental carcinogens, reactive oxygen species and chemotherapeutic

Association between allelic polymorphisms of metabolizing enzymes (CYP 1A1, CYP 1A2, CYP 2E1, mEH) and occurrence of colorectal cancer in Hungary.

Abstract: Background: Genetic polymorphisms of metabolizing enzymes may affect the risk of cancer formation in humans. Since the diet can contain polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs), the relationship between polymorphisms of enzymes involved in PAH and HA metabolism and the occurrence of sporadic colorectal cancer was studied. Patients and Methods: Five hundred colorectal cancer patients and 500 controls were genotyped for cytochrome P450 enzymes (CYP) 1A1 Ile/Val, CYP 1A2*1F, CYP 2E1 c1/c2, microsomal epoxy hydrolase (mEH) exon 3 Tyr113His and exon 4 His139Arg polymorphisms by allele-specific polymerase chain reaction (PCR) or PCR-restriction fragmenth length polymorphism (RFLP). Results: The presence of CYP 1A1 Val, CYP 2E1 c2 and mEH exon 3 His alleles was statistically significantly associated with the occurrence of colorectal cancer (OR: 1.44 95% CI: 1.04-2.00; OR: 1.74 95% CI: 1.15-2.65; OR: 1.79 95% CI: 1.10-2.92, respectively). Conclusion: These findings suggest that allelic polymorphism of metabolizing enzymes play an important role in human colorectal carcinogenesis by affecting the metabolism of dietary carcinogens.

Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population.

Abstract: Background: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. Patients and Methods: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. Results: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. Conclusion: The complex analysis of these factors may provide the basis for personal risk assesement and an opportunity for individualised therapy.

New Insights into the Role of Inflammation in the Pathogenesis of Atherosclerosis

Abstract: Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, smooth muscle cell proliferation, cell apoptosis, necrosis, fibrosis, and local inflammation. Immune and inflammatory responses have significant effects on every phase of atherosclerosis, and increasing evidence shows that immunity plays a more important role in atherosclerosis by tightly regulating its progression. Therefore, understanding the relationship between immune responses and the atherosclerotic microenvironment is extremely important. This article reviews existing knowledge regarding the pathogenesis of immune responses in the atherosclerotic microenvironment, and the immune mechanisms involved in atherosclerosis formation and activation.

Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer.

Abstract: A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53-targeted therapies.

The Evolution of Antiplatelet Therapy in the Treatment of Acute Coronary Syndromes

Abstract: Our knowledge of the mechanisms of platelet-mediated thrombosis has increased dramatically over the last 40 years This increased understanding has identified treatment strategies for acute coronary syndromes (ACS) by targeting key mediators of platelet activation and aggregation processes Aspirin (acetylsalicylic acid) monotherapy improves patient outcomes by irreversibly inhibiting the cyclooxygenase (COX)-1 enzyme in the arachidonic acid pathway The later-developed thienopyridines, prodrugs that irreversibly inhibit the P2Y12 receptor, and therefore adenosine diphosphate (ADP) binding, further enhance platelet inhibition and patient outcomes The thienopyridine clopidogrel has been the standard of care, but it is limited by variable response and treatment failure A more potent thienopyridine, prasugrel, requires fewer hepatic metabolic steps for activation, and elicits significantly improved outcomes for patients with ACS The increased potency of prasugrel is associated with an increase in Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding compared with clopidogrel Ticagrelor represents a new chemical class of agents called the cyclopentyltriazolopyrimidines It interacts reversibly with the platelet P2Y12 receptor, and does not require metabolic bioactivation for activity Data show a significant improvement in ischaemic outcomes, including mortality, for ticagrelor compared with clopidogrel, without an increase in overall major bleeding, although non-coronary artery bypass graft bleeding is increased Glycoprotein IIb/IIIa targeted agents (abciximab, tirofiban and eptifibatide) are also used in ACS patients undergoing percutaneous coronary interventions These inhibitors utilize a different mechanism of action by preventing fibrinogen-mediated platelet aggregation Other therapeutic strategies for platelet inhibition are being evaluated, including the investigative protease-activated receptor (PAR)-1 and thromboxane A2 antagonists This review highlights the mechanisms of action of these agents, and the continuing evolution of ACS therapy