Conjugation with Tris Decreases the Risk of Ketoprofen-Induced Mucosal Damage and Reduces Inflammation-Associated Methane Production in a Rat Model of Colitis

We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments

Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse

Impact of Coronary Plaque Vulnerability on Acute Cardiovascular Events – Design of a CT-based 2-year Follow-up Study

With coronary artery disease (CAD) projected to remain the leading cause of global mortality, prevention strategies seem to be the only effective approach able to reduce the burden and improve mortality and morbidity. At this moment, diagnostic strategies focus mainly on symptomatic patients, ignoring the occurrence of major cardiovascular events as the only manifestation of CAD. As two thirds of fatal myocardial infarction are resulting from plaque rupture, an approach based on the “vulnerable plaque” concept is mandatory in order to improve patient diagnosis, treatment, and, by default, prognosis. Given that the main studies focus on a plaque-centered approach, this is a prospective observational study that will perform a complex assessment of the features that characterize unstable coronary lesions, in terms of both local assessment via specific coronary computed tomography angiography markers of coronary plaque vulnerability and systemic approach based on serological markers of systemic inflammation in patients proved to be “vulnerable” by developing acute cardiovascular events

Association between the Incidence of Sudden Cardiac Arrest and the Location of Culprit Lesions in STEMI Patients – Design of a Prospective Clinical Study

Out-of-hospital cardiac arrest (OHCA) has a poor prognosis and is the most severe complication of any cardiac event. It is known from previous studies that the location of the culprit lesion in ST-segment elevation myocardial infarction (STEMI) patients with cardiac arrest may affect the post resuscitation survival rate. However, due to the low number of cases, the association between the localization of the culprit lesion within the coronary tree and the occurrence of cardiac arrest is not widely discussed, because resuscitated cardiac arrest patients are excluded from the vast majority of clinical trials. This is a prospective observational study that aims to develop a prediction model for OHCA in patients who present with STEMI, based on differences related to culprit lesion location. The primary objective of the study is to evaluate the differences related to the location of the culprit lesion in patients with STEMI who present OHCA versus patients without cardiac arrest

The Impact of Coronary Artery Calcification on Long-Term Cardiovascular Outcomes

Decades of research and experimental studies have investigated various strategies to prevent acute coronary events. However, significantly efficient preventive methods have not been developed and still remains a challenge to determine if a coronary atherosclerotic plaque will become vulnerable and unstable. This review aims to assess the significance of plaque vulnerability markers, more precisely the role of spotty calcifications in the development of major cardiac events, given that coronary calcification is a hallmark of atherosclerosis. Recent studies have suggested that microcalcifications, spotty calcifications, and the presence of the napkin-ring sign are predictive vulnerable plaque features, and their presence may cause plaque instability