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Student Researchers' Society Topics

Chronic pancreatitis is a progressive inflammatory disease leading to irreversible morphological changes and impairment of both exocrine and endocrine functions. Genetics plays an important role in the pathogenesis of chronic pancreatitis, especially in children. Over the past 20 years the role of genetic factors in the etiology of chronic pancreatitis has been extensively studied and a mechanistic model in which premature trypsinogen activation plays a central pathogenic role has been established. More recently, an alternative pathomechanism unrelated to accelerated intrapancreatic trypsinogen activation has been revealed, in which mutation-induced misfolding and consequent ER stress lead to acinar cell damage and pancreatitis. Using animal models of genetically determined chronic pancreatitis we aim to study both pathomechanisms, the trypsin-dependent and the ER stress related pathways in vivo. Moreover, we also focus on the identification of new genetic risk factors in chronic pancreatitis using candidate gene association studies.

Our laboratory was recently established as part of the “Center for Pancreas Disorders” within the Institute for Translational Medicine of the University of Pécs. In the center the students will have the opportunity to master different techniques used in molecular genetics (DNA/RNA isolation, PCR, RT-PCR, Sanger sequencing, mutagenesis, Western blot), biochemistry (affinity chromatography, enzyme activity measurements), cell culture and mouse model experiments.

The students also will have the opportunity to perform some of the experiments in the laboratory of Professor Miklos Sahin-Toth (Boston University), who is a world-renowned researcher in the field of chronic pancreatitis focusing on the genetic background of the disease. Professor Sahin-Toth has a dual role in the projects; he is the director of the Center for Pancreas Disorders at the University of Pécs and he will also serve as an international collaborator.

Co-supervisor: Dr. TINUSZ, Benedek

The two main histological types of esophageal cancers are squamous cell carcinomas and adenocarcinomas. Traditionally, the former is much more common, however, during the last few decades the incidence of adenocarcinomas has been rising so steeply that in some developed countries it has already surpassed squamous cell carcinomas in terms of occurence rates. There are no known nation-wide, large scale studies in Hungary that could prove this trend.

Our aim with this study is to gather data concerning the epidemiological state, risk factors and management system of patients with esophageal cancers. These findings are necessary for the introduction of certain endoscopic procedures used to treat early stage esophageal cancers.

Co-supervisor: Dr. SZAKÁCS, Zsolt

Cystic fibrosis (CF) is caused by a loss of function mutation in the CFTR chloride channel (most commonly deltaF508), which causes abnormalities in the function of the external glands. It is a complex disorder that is mainly associated with severe respiratory and digestive symptoms and usually affects the pancreas as well. Pancreatic parenchymal damage may occur early in life, even in utero, leading to the development of cystic fibrosis-related diabetes (CFRD). The disease, in addition to other rare causes of diabetes, is classified as type 3 diabetes mellitus.

In this topic, we will perform a meta-analysis to investigate methods used to diagnose CFRD. The purpose of the diagnostic test accuracy meta-analysis is to compare different modalities to each other, thereby ranking them. According to current guidelines, the gold standard diagnostic test is the oral glucose tolerance test (OGTT), but several other modalities are available (e.g., continuous glucose monitoring, fasting blood glucose levels and haemoglobin A1C). Our results can contribute to the selection of the best (and most cost-effective) diagnostic option.

Co-supervisor: Prof. Dr. MOLNÁR, Lajos Zsolt

The severe form of acute pancreatitis is similar in the aspect of pathophysiology and course of disease to septic shock. Both clinical conditions are associated with high mortality. Since the incidence of the severe cases of acute pancreatitis is rare (about 10% of all acute pancreatitis cases), there is only limited information about the course of disease, diagnostics and therapy. The aim of our study group is to establish an extensive research program to study patients who require intensive or subintensive care. In addition to retrospective, prospective and observational studies we are also planning prospective randomized controlled trials. One of our main goals is to expand our knowledge on extracorporal cytokine adsorption therapy, therefore we are initiating multicenter clinical trials on the cytokine adsorption therapy in patients with septic shock and with severe acute pancreatitis.

Celiac disease is an immune-mediated disorder, which affects approximately 1% of the population. The altered immune response is the consequence of the interplay of genetic (HLA-haplotypes) and environmental exposures (that is, the ingestion of gluten). The disease has several intestinal and extraintestinal signs and symptoms, the latter group includes metabolic bone disease. The pathophysiological background of osteoporosis and osteopenia is rather complex: both the exposure to chronic systemic inflammation and the malabsorption with the consequent calcium and vitamin D deficiency are important contributors. The single known effective therapy is the lifelong deprivation of gluten (i.e., gluten-free diet).

Whether metabolic bone disease is reversible with adequate gluten-free diet has remained controversial. The aim of the research topic is to perform a meta-analysis, in which we assess bone mineral density at the time of diagnosis and later on gluten-free diet to determine the change both in children and adults. The findings may contribute to the establish the indication of DEXA-scans with effective timing.

The diagnosis of celiac disease is sometimes challenging. In addition to the extraordinary variability in clinical presentation, severe intestinal and extraintestinal symptoms and accompanying diseases may develop. Some patients complain of typical gastrointestinal symptoms whereas others exhibit an atypical presentation (Oslo classification). The phenotype is often complicated by the development of autoimmune diseases and celiac complications. It is not clear how factors determine the clinical phenotype. The degree of small intestinal damage does not provide a satisfactory explanation for a phenomenon describing that patients may suffer from severe malabsorption or be asymptomatic with total villous atrophy.

In this project, we focus on the clinical phenotype of celiac disease by approaching the diverse disease course from different aspects. Concomitant diseases (especially the autoimmune diseases) and special subclinical alterations predisposing to higher complication rates, e.g., the association between hemorrheological parameters and the increased risk of thrombosis, are in the focus of interest.

Co-supervisor: Dr. PÁRNICZKY, Andrea

Cystic fibrosis (CF) is caused by a loss of function mutation in the CFTR chloride channel (most commonly deltaF508), which causes abnormalities in the function of the external glands. It is a complex disorder that is mainly associated with severe respiratory and digestive symptoms. In CF patients, the lungs become more susceptible to bacterial infections and may sustain chronic lung injury, leading to respiratory failure and even to death.

In the study, we use the Hungarian CF Registry to investigate the relationship between the clinical picture and microbiological profile of CF-associated lung injury. The aim of the research is to evaluate the microbiological and clinical features of the Hungarian CF population with statistical analysis. Results can contribute to the improvement of patient’s quality of life and medical attendance.

Co-supervisor: Dr. PÉTERVÁRI, Erika

Cholecystokinin administered peripherally or centrally elicits anorexigenic effects, but its complex peripheral or central catabolic effects may be divergent. In the periphery, the role of CCK1- receptors may be dominant, in the brain, CCK acts mainly via CCK2 receptors, but overlaps may occur. We plan to clarify the the role of CCK1 and CCK2 receptors in the development of anorexigenic and metabolic effects via the peripheral and central application of specific CCK1 and CCK2 receptor antagonists. Acute (intraperitoneal/intracerebroventricular) injections and similar chronic infusions will be applied using biotelemetry and indirect calorimetry. Our previous results show, that CCK-effects depend on age and nutritional state, so the above outlined experiments will be carried out in different age-groups of rats characterized by different nutritional states.

Obstructive lung diseases affect more and more people worldwide. The symptoms of these diseases grow more severe during aging leading to a decline in the quality of life. The aim of the research is to study the effects of different diets/nutritional states and those of physical training on the symptoms of obstructive lung diseases in men and women.

Age-related regulatory alterations may be assumed in the background of middle-aged obesity and aging anorexia since they also appear in other mammals. Our previous studies described such regulatory alterations of the central catabolic melanocortin system: a weak catabolic responsiveness to alpha-melanocyte stimulating hormone in middle-aged and a strong one in old age-groups. Corticotropin releasing factor (CRF) and urocortins are important catabolic peptide mediators downstream to the melanocortins. Their effects are mediated by CRF1 and CRF2 receptors. In the PhD program we aim to investigate the age- and nutritional state-associated alterations in the central corticotropin system (and those of its receptors). Animal experiments will carried out in different age-groups (from juvenile to old) of laboratory rodents. Regarding nutritional state, we establish ad libitum fed, diet-induced obese and calorie-restricted groups withing the age-groups. During the analysis of central acute and chronic corticotropin responsiveness, food intake is to be recorded in an automated FeedScale system, circadian rhythm of core temperature, heart rate, spontaneous locomotor activity in a biotelemetric system (MiniMitter, Respironics). These measurements will be complemented by the registration of oxygen consumption, core and tail skin temperature (the latter indicates heat loss) in an Oxymax system (Columbus) for indirect calorimetry.

The obesity epidemic is one of the most serious public health challenges in the European region: more than one in two adults is overweight or obese. Obesity is the basis for the development of major non-infectious diseases (such as metabolic syndrome, hypertension, insulin resistance, type 2 diabetes mellitus, dyslipidemia, subsequent pathological vascular changes and atherosclerosis). Therefore, obesity reduces life expectancy and reduces quality of life.
In the background of cardiovascular complications, endothelial dysfunction develops before the development of atherosclerosis. The chronic inflammatory state of obesity causes poor control of the endocrine and paracrine effects of adipocyte-derived factors, which disrupts vascular homeostasis and contributes to the disruption of endothelial vasodilatory effects and subsequent hypertension. In our experiments, we aim to observe, reverse and prevent abnormal vascular functions after obesity caused by high-fat diet and in type 1 and type 2 diabetes mellitus with a novel therapeutic approach by activating the PAC1, VPAC1 and VPAC2 receptors.

Co-supervisor: Dr. RUMBUS, Zoltán

Systemic inflammation of the body (e.g., sepsis) is the 10th most common cause of death in the world, demanding approx. 1400 lives daily. In Hungary, ~9000 patients are treated in intensive care units because of sepsis with a mortality rate of 30-60%. Systemic inflammation is strongly associated with changes of body temperature, which is also included in its clinical diagnosis. Most patients have fever, but many develop a body temperature lower than normal (hypothermia). For the successful intensive therapy and for the reduction of the mortality rate of systemic inflammation, it is inevitable to carefully explore the involved physiological and pathological mechanisms, which are still subjects of research.

Based on previous studies the capsaicin receptor (recently known as TRPV1 channel) plays an important role in the maintenance of normal body temperature and body mass. By utilizing rats with functionally impaired TRPV1 channels (capsaicin desensitized), we can model the effects of the lack of TRPV1 in vivo. We want to investigate how the lack of TRPV1 influences the age-related changes of energy balance with measuring the changes of body temperature, body mass and the changes of the effects of central and peripheral an/orexigenic substances in systemically and intra-abdominally desensitized rats as a function of age.

Neuropeptides released from capsaicin-sensitive nerve endings play an important role in inflammatory processes. It is also known that capsaicin desensitization – through not yet clarified mechanisms – influences the development of bacterial lipolysaccharide (LPS)-induced fever. We want to investigate the role of capsaicin-sensitive nerve ending derived neuropeptides (e.g., substance P, PACAP) and of their receptors in the development of LPS-induced body temperature response, also, to study their effects on the activation of thermoeffectors (heat production, heat conservation) that are recruited in the temperature response.

Fever, hypothermia as well as obesity and cachexia are results of the dysregulation of energy balance. In our research, we plan to study, which mechanisms play a role in the development of energy imbalance. We assume that ion channels (formerly known as the capsaicin receptor, recently TRPV1), which can be activated by capsaicin, the pungent ingredient of hot peppers, furthermore, age-related changes in the effects of certain (anabolic and catabolic) molecules on food intake and on metabolism possess an outstanding role in these mechanisms. Based on the above, we plan to clarify the role of TRPV1 and other TRP channels in the regulation of body temperature and of body mass with special focus on the age-related changes in their function.