Research Eric van Breda

Abstract

Out of the 80 million scars formed every year in the developed world, 40-70% will develop into problematic, stiff, thick, painful, itchy, and pigmented scars. These scars not only cause physical discomfort but also have profound psychosocial impacts. The pursuit of effective treatments is crucial, and mechanotherapy, specifically extracorporeal shockwave therapy (ESWT), has emerged as a promising modality. However, the lack of a standardized approach and an in-depth understanding of its mechanotransduction mechanisms limits its potential. In the long term, our research aims to pioneer a mathematical model that encapsulates cellular, molecular, and physical responses to ESWT, inspired by mathematical burn scar models yet innovative in its inclusion of mechanotherapy. This model will be the first to simulate the stimulus-response effect of mechanotherapy, facilitating the customization of ESWT modalities in clinical settings and fostering a scar-centered approach in scar rehabilitation. The central objective of our study is to dissect how ESWT influences different types of skin and scar tissue at the cellular and molecular levels. We propose a novel in vitro investigation using human dermal models of varying extracellular matrix stiffness. This approach enables us to standardize ESWT application and analyze histological, cellular, and molecular outcomes, thus informing our mathematical model. Our research stands at the intersection of innovative technology and practical therapeutics, striving to elucidate the optimal application of ESWT. By integrating comprehensive literature reviews, data from clinical trials, and rigorous in vitro experimentation, we aspire to transform the landscape of scar management. The long-term outcome is a predictive framework that revolutionizes mechanotherapy protocols, tailored to individual scar characteristics and healing stages. This project not only holds the potential to enhance the quality of life for those affected by hypertrophic scarring but also paves the way for evidence-based advances in scar rehabilitation.

Researcher(s)

• Promoter: Van Daele Ulrike
• Co-promoter: van Breda Eric
• Fellow: Peetersem Charlotte

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Doxorubicin (DOX) is a widely used and highly effective chemotherapeutic agent with severe side effects, affecting the quality of life of cancer patients and survivors. DOX-induced skeletal muscle toxicity, especially muscle wasting and dysfunction, is of particular concern as it increases morbidity and mortality rates. In the current proposal, we aim to investigate the role of myokines and miRNAs within the mechanisms of DOX-induced skeletal muscle wasting through an in vitro (C2C12 cell line) and in vivo (mice) model. Identification of these myokines and miRNAs, that are expressed and exert their action in skeletal muscle, offer a novel theoretical basis to unravel the underlying cellular and molecular mechanisms and provide novel insights in the diagnosis and treatment of skeletal muscle wasting following DOX-treatment. We hypothesize that myokines and miRNAs play a crucial role in the pathogenesis of DOX-induced skeletal muscle wasting. In addition, we will study the potential cellular and molecular counteracting effects of muscle contraction on muscle wasting by 1) electrical pulse stimulation on DOX-treated C2C12 cells and 2) single exercise bouts in mice immediately before each DOX-cycle. We hypothesize that exercise is a feasible strategy in clinical practice to prevent DOX-induced muscle wasting. Finally, to improve clinical translatability we will also study the therapeutic use of single exercise bouts in a murine cancer cachexia model treated with DOX.

Researcher(s)

• Promoter: van Breda Eric
• Co-promoter: Guns Pieter-Jan
• Co-promoter: Van Craenenbroeck Emeline
• Fellow: Van Asbroeck Birgit

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Cancer survival has increased significantly over the last decades because of improved screening and the development of novel therapies. The downside of this positive evolution is that cancer treatment-related adverse events affecting the quality of life of cancer survivors has become an emerging concern. Physical long-term side effects of anthracycline chemotherapy, such as doxorubicin (DOX) and Cisplatin (CIS), include cardiovascular complications (heart failure), peripheral fatigue and muscle mass loss (wasting). While the cardiovascular toxicity of DOX has been extensively studied, this project aim to investigate the effects of DOX and/or CIS on skeletal muscle structure and (mitochondrial) metabolism. Additionally, we will evaluate the possible beneficial effect of physical exercise as a strategy to protect against DOX and CIS induced myotoxicity. This project aims to lay the foundation of a novel joint research line of the research groups of Movant, Cardiovascular Disease and Physiopharmacology to exploit scientific and operational synergies.

Researcher(s)

• Promoter: van Breda Eric
• Co-promoter: Guns Pieter-Jan
• Co-promoter: Van Craenenbroeck Emeline
• Fellow: Van Asbroeck Birgit

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Severe burns cause a cascade of unwanted effects such as an overdrive in metabolism, loss of muscle tissue, and loss of the body's ability to effectively handle glucose as an energy source and an enhanced inflammatory state. Against common belief, these side effects have shown to persist for years, and cause long-term consequences such as a reduced physical fitness and a higher risk of developing diabetes. Despite many research efforts, much of these persistent side effects that occur in burns are not well understood. Efforts to counteract the negative effects on metabolism, the loss of muscle tissue and to prevent or lessen the amount of the inflammation have not yet been successful. Exercise rehabilitation has the potential to, at least partly, prevent and/or restore the negative consequences as has been shown in other critically ill hospitalised patients. This project will, therefore, shed more light onto 1) the short- and long-term effects of severe burns on energy metabolism, loss of muscle tissue, and inflammation in adults, and 2) the effect of an 8-week exercise rehabilitation programme during the initial period of hospitalization on these parameters. In order to successfully execute this project, we will study patients from Belgium and Chinese burn centres to get a better understanding of the bodily derangements, which will lay a foundation for better future care of burn patients.

Researcher(s)

• Promoter: Van Daele Ulrike
• Co-promoter: van Breda Eric
• Fellow: Schieffelers David

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Severe burned patients undergo rapid increases in metabolism (hypermetabolism) and increased energy expenditure caused by the initial inflammatory and humoral responses. These responses also elicit, on top of the bed rest period, a cascade of negative reactions leading to additional muscle wasting. Muscle wasting itself leads to insulin resistance and may have long-term health consequences. Some of these effects persist from the first few days following severe burn injury to as long as three years later after wound closing. Although insulin resistance is assumed to be triggered by several catabolic factors, an important contributor to insulin resistance is muscle wasting itself. Insulin-resistance, may eventually lead to diabetes mellitus and is a long-term complication of severe burn patients which has major implications for future morbidity and mortality. Muscle wasting is a hallmark of burns but the underlying pathophysiological pathways are not well understood. The main aim of this project is to investigate the underlying mechanisms of muscle wasting (atrophy) in a rat model of severe burns (>40% TBSA). The first part of the study will focus on the effects of severe burn trauma in rats on the metabolomic profile of skeletal muscle, liver and blood. Secondly, we will focus on the same outcome measures during muscle disuse by means of rat hindlimb suspension with or without exercise. Thirdly, immune-histochemical, Western-blotting and biochemical analysis of the skeletal muscle activation and content of satellite cells, muscle capillarisation, autophagy and/or associated metabolic signalling pathways will be done. Finally, chemical blocking of myostatin as muscle wasting regulator will be investigated. The results of this project will be linked to the results of our ongoing clinical FWO project on exercise therapy in severely burned patients.

Researcher(s)

• Promoter: Van Daele Ulrike
• Co-promoter: van Breda Eric
• Fellow: Dombrecht Dorien

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Both modern and classical dance are characterized by a large number of injuries caused by overload. This overload is defined as "an increase in training load resulting in a decrease in performance". Overtraining in combination with poor nutrition can lead to menstrual irregularities, which can adversely affect reproductive functions and bone mass. The combination of reduced energy availability, menstrual irregularities and reduced bone mass was called the "Female Athlete Triad (FAT)". In 2014, the International Olympic Committee (IOC) introduced the term Relative Energy Dysfunction in Sport (RED-S). It replaced the term and the syndrome that was previously called "Female Athlete Triad", which indicated the combination and interaction of a disturbed diet, irregular menstruation and reduced bone density in sports women. Recent scientific insights had made it clear that the term "Female Athlete Triad" was no longer appropriate. The RED-S syndrome refers to 'reduced physiological functioning caused by a relative energy deficiency and includes, but is not limited to, disorders of (1) metabolism, (2) menstruation, (3) bone health, (4) immunity, (5) protein synthesis and (6) cardiovascular health. However, there is a lack of studies to this day that study the interrelationships between the various conditions. Low energy availability (LEA, low energy availability) is the main cause of this complex syndrome. It is not so much a disturbed eating pattern as a disturbed energy balance that is at the root of this problem. This has an impact on many more processes in the body than was initially thought. It also not only affects women, but can also occur in male athletes. The main objective of this study is "to unravel energy metabolic aspects of RED-S in elite adolescent and adult dancers and to study the relationship with menstrual irregularities, bone quality and complaints."

Researcher(s)

• Promoter: van Breda Eric
• Co-promoter: Roussel Nathalie

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

The general purpose of this study is to elucidate psychological and social risk factors for low back pain (LBP) in highly physically active adolescents. Using a qualitative research design, we will explore perceived causes (psychological and social) of LBP using female pre-professional dancers as a case study. This will lay the foundation for fundamental prospective studies examining causes of LBP in adolescents. Low back pain (LBP) is the leading cause of disability worldwide. The prevalence of LBP rapidly increases during adolescence, especially in females. The multidimensional nature (including biological, psychological and social factors) of LBP is widely recognized in adults, but has, despite the fact that LBP during adolescence is a risk factor for spinal pain in adulthood, rarely been investigated in adolescents. Elite adolescent dancers are a model population to unravel the etiology of adolescent LBP as they are a homogenous group that is highly physically active and that is at risk for developing LBP. The novelty of our approach is the unraveling of LBP from a multidisciplinary perspective in adolescents at risk for developing LBP in a challenging period of their life. The proposed qualitative methodology will allow to explore these factors in more depth, as validated questionnaires to examine psychological and social factors in adolescent dancers are lacking. The collaboration in this project between several disciplines will allow to obtain a more detailed insight in the person as a whole, including a great part of the individual and contextual factors underlying the etiology of LBP in highly active adolescents. More importantly, the results of the project will lay the foundation for the continuation of the research in the etiology of LBP in dancers and adolescents.

Researcher(s)

• Promoter: Roussel Nathalie
• Co-promoter: Gielen Pascal
• Co-promoter: van Breda Eric

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Severe burns cause a cascade of unwanted effects such as an overdrive in metabolism, loss of muscle tissue, and loss of the body's ability to effectively handle glucose as an energy source and an enhanced inflammatory state. Against common belief, these side effects have shown to persist for years, and cause long-term consequences such as a reduced physical fitness and a higher risk of developing diabetes. Despite many research efforts, much of these persistent side effects that occur in burns are not well understood. Efforts to counteract the negative effects on metabolism, the loss of muscle tissue and to prevent or lessen the amount of the inflammation have not yet been successful. Exercise rehabilitation has the potential to, at least partly, prevent and/or restore the negative consequences as has been shown in other critically ill hospitalised patients. This project will, therefore, shed more light onto 1) the short- and long-term effects of severe burns on energy metabolism, loss of muscle tissue, and inflammation in adults, and 2) the effect of an 8-week exercise rehabilitation programme during the initial period of hospitalization on these parameters. In order to successfully execute this project, we will study patients from Belgium and Chinese burn centres to get a better understanding of the bodily derangements, which will lay a foundation for better future care of burn patients.

Researcher(s)

• Promoter: Van Daele Ulrike
• Co-promoter: van Breda Eric
• Fellow: Schieffelers David

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project

Abstract

Severe burned patients undergo rapid increases in metabolism (hypermetabolism) and increased energy expenditure caused by the initial inflammatory and humoral responses. These responses also elicit, on top of the bed rest period, a cascade of negative reactions leading to additional muscle wasting. Muscle wasting itself leads to insulin resistance and may have long-term health consequences. Some of these effects persist from the first few days following severe burn injury to as long as three years later after wound closing. Although insulin resistance is assumed to be triggered by several catabolic factors, an important contributor to insulin resistance is muscle wasting itself. Insulin-resistance, may eventually lead to diabetes mellitus and is a long-term complication of severe burn patients which has major implications for future morbidity and mortality. Physical exercise has been shown to affects both the metabolism as well as skeletal muscle function in oncology, cardiac patients, obstructive lung diseases and diabetic patients. In addition, physical exercise in critically-ill patients has also been shown to have beneficial effects on general health outcome parameters. Therefore, in the present study we will investigate the effects of severe burns [≥ 30 % total body surface area (TBSA)] on energy expenditure, hypermetabolism (especially insulin and glucose homeostasis) and muscle function (strength). Besides the fundamental research questions we will investigate the effect of an 8 week (3 times/week) rehabilitative exercise strength training on energy expenditure, hyper metabolism and muscle function. For the long-term effects we will investigate the Quality of Life (QoL) in patients undergoing such an additional rehabilitative program on top of standard-care. For this purpose we will use both general as well as burn specific questionnaires regarding QoL.

Researcher(s)

• Promoter: Van Daele Ulrike
• Co-promoter: Gebruers Nick
• Co-promoter: van Breda Eric
• Fellow: Schieffelers David

Research team(s)

• Movement Antwerp (MOVANT)

Project type(s)

• Research Project