Doctoral Program - Ph.D.

2020

Effects of complement C5a inhibitor therapy on macro- and microcirculatory disturbances in experimental models of non-occlusive mesenteric ischemia

Thesis supervisor: Gabriella Varga; co-supervisor: Dániel Érces

Description

Non-occlusive mesenteric ischemia (NOMI) develops in the presence of anatomically intact mesenteric vessels without the signs of physical occlusion. The process can lead to severe circulatory disturbances, affecting large areas of the splanchnic region. Early, targeted therapy is needed but the diagnosis is difficult, mainly due to the lack of specific signs, and besides, the pathophysiology is only partially understood. It is assumed that a long-lasting vasoconstriction is accompanied by inflammatory activation leading to severe mucosal damage of the small intestines. Therefore, according to the present knowledge, vasodilator therapy should be started immediately, including intraarterial administration of papaverin and prostaglandin.

In our experimental studies the role of the complement system and specifically, the role of C5a will be investigated. In these protocols a synthetic, antisense peptide is used as selective C5a inhibitor in large and small animal models (swine and rat, respectively) of NOMI.

Study I: It is well known that the C5a complement factor has a central role in the development of hemodynamic alterations after cardiogenic shock. C5a is produced by enzymatic cleavage during the activation of the complement system and it is able to contribute to the inflammatory process by many ways, including chemotactic activity, induction of histamine release from mast cells, or activation of cyclooxygenase and lipoxygenase enzymes.

The experiments are performed on Vietnamese minipigs, with cardiac tamponade. Following the tamponade, the gastrointestinal microcirculation is impaired because of the vasoconstriction of the splanchnic area and we hypothesize that the administration of a C5a inhibitor, the circulatory disturbances can be reduced or ceased.

Studis II-III: These experiments are performed on Sprague-Dawley rats. The short (less than 3 hours) and long-term (over 24 hours) inflammatory complications of NOMI are investigated in vivo, during partial aortic occlusion, induced by mechanical clamping of the abdominal aorta. We hypothesize that the C5a inhibitor treatment influences the inflammatory, micro- and macrohemodynamic consequences of NOMI. We hope that by this way the significance of complement activation can be demonstrated, and the macro- and microhemodynamic alterations and the consecutive inflammatory process can be reduced, finally leading to the reduction of micro- and macroscopic epithelial damage in the small intestine.

Required language skills: English

Number of acceptable students: 1

Application deadline: 2020-08-14

Studies on the efficacy of simulation skills training in surgery

Thesis supervisor: Andrea Szabó

Co-tutor: Prof. Jorge Correia-Pinto, Hospital of Braga, University of Minho, ICVS, Braga, Portugal

Participant: Dr. Péter Etlinger

Description:

In the present studies, learning curves of pediatric residents with different levels of laparoscopic experience are compared: an advanced group, where pediatric surgery fellows has previous experience of basic laparoscopic procedures in humans, and a novice, beginner group with no previous experience with minimally invasive surgery, but underwent a basic systematic box-trainer course in a preparatory period. Using a multimodal evaluation approach, we examine (1) how a pediatric surgery-oriented standardized training is performed in vivo, and weather the use of laboratory animals influences the learning curve of the participants, (2) how to quantify the improvement of these skills and (3) how many repetitions of these tasks will enable the participants to carry out complex advanced laparoscopic procedures in humans (translation).

Required language skills: English

Recommended language skills (in Hungarian): English B2 level

Number of acceptable students: 1

Application deadline: 2020-06-18