7th International Congress of Pathophysiology

7th International Congress of Pathophysiology Faculty of Sciences, University Mohammed V Rabat, Morocco 4-7 September 2014

Message from the Congress Chairman Welcome to Rabat, Welcome to Morocco. Mohammed V University is pleased to host this important meeting of the International Society for Pathophysiology, the first being held in Africa. With significant participation of leading researchers from around the world, we will be discussing the latest findings in several areas impacting human health and wellbeing, as well as considering the history of pathophysiology and recent developments in teaching methodology. The program of this meeting is rich, with four plenary lectures, ten symposia, three oral communication sessions and more than 120 posters. I hope that we have succeeded in providing an appropriate framework for exchanging ideas and developing networks, laying the ground for future collaborative efforts. Morocco, at the crossroads of continents, enjoys a diverse cultural and linguistic identity. Rabat has just celebrated its first century as the capital city. A world heritage site, several of its monuments deserve a visit during your stay. Rabat is a welcoming and safe city. Nevertheless, as you walk about in crowded areas or ride the tram, the usual precautions of seasoned travelers are in order. I trust you will enjoy a satisfying professional and cultural experience during this conference. Finally, I would like to thank all those who, in Morocco and around the world, made this event possible.

Wail Benjelloun, Congress Chairman

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CONTENTS

INDEX

19 25 51 69 165

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4-7 September 2014 Faculty of Sciences, Mohammed V University , Rabat - Morocco

PLENARY LECTURE ABSTRACTS SYMPOSIUM ABSTRACTS ORAL PRESENTATION ABSTRACTS POSTER ABSTRACTS

7th International Congress of Pathophysiology

ORGANIZING COMMITTEES 7 9 SCIENTIFIC PROGRAM ABSTRACTS

ISP Council: 6

Han, Q. (China, Past President) Monos, E. (Hungary, Past President) Hamet, P. (Canada, President) Arkhipenko, Y. (Russia, Vice President) Greenwald, S. (England, Vice President) Zhang, Y. (China, Vice President) Rosivall, L. (Hungary, Treasurer) Hänninen, O. (Finland, Editor of Pathophysiology) Adeniyi, K. (Nigeria) Atalay, M. (Turkey) Benjelloun, W. (Morocco) Cowley, A. (USA) Djuric, D. (Serbia) Fry, CH. (England) Grachev, SV. (Russia) Jakovljevic, V. (Serbia) Kovač, Z. (Croatia) Laitinen, T. (Finland) Mahmoudian, M. (Iran) Matsuo, O. (Japan) Meigal, A. (Russia) Morita, H. (Japan) Navasardyan, G. (Armenia) Orlov, S. (Canada) Rodriguez, RR. (Argentina) Sakata, T. (Japan) Scholle, H-Ch. (Germany) Sejersted, OM. (Norway) Štrbák, V. (Slovakia) Szollár, LG. (Hungary) Vozeh, F. (Czech Republic) Wang, J. (China) Kryzhanovsky, G. (Russia, Founder Honorary President) Korpas, J. (Slovakia, Honorary Council Member) Oomura, Y. (Japan, Honorary Council Member) Yoshikawa T. (Japan, Honorary Editor of Pathophysiology)

AAPS Council:

Amal Saeed (Sudan, President) Prem Gathiram (Republic of South Africa, Vice President) Yasser El-Wazir (Egypt, Secretary General) Saartjie Roux (Republic of South Africa, Treasurer) Olusoga Sofola (Nigeria, Member) Faadiel Essop (Republic of South Africa, Member) Frank Mojiminiyi (Nigeria, Member) Magda Ibrahim (Egypt, Member) Anthony Ebeigbe (Nigeria, Member)

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Local Organizing Committee:

Benjelloun Wail (Faculty of Sciences, Mohammed V-Agdal University, Rabat) Lakhdar-Ghazal Nouria (Faculty of Sciences, Mohammed V-Agdal University, Rabat) Bouzoubaa Fouzia (Faculty of Sciences, Mohammed V-Agdal University, Rabat) Ouzir Mounir (Faculty of Sciences, Mohammed V-Agdal University, Rabat) El Ouahli Allaa (Faculty of Sciences, Mohammed V-Agdal University, Rabat) Kaarouch Ismail (Faculty of Sciences, Mohammed V-Agdal University, Rabat)


National Committee:

Lakhdar Ghazal Nouria (Rabat, Morocco) Amzazi Saaid (Rabat, Morocco) Errami Mohammed - Secretary Treasurer (Tetouan, Morocco) Gharbi Mourad (Rabat, Morocco) Benazzouz Hamid (Bordeaux, France) Chait Abderrahman (Marrakech, Morocco) Boussaoud Driss (Marseille, France) Battas Omar (Casablanca, Morocco) Ba Mhammed Saadia (Marrakech, Morocco) Benomar Ali (Rabat, Morocco) El Ouazzani Taibi Seloua (Fez, Morocco) El Allali Khalid (Rabat, Morocco) Bagri Abdallah (Settat, Morocco)

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Homage to the Founder Honorary President Prof. Georgy N. Kryzhanovsky &KDLU +DPHW3DYHO(University of Montreal, Montreal, Canada)

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68% teaching hours, visibility of pathophysiology subjects in curricular designs, university appreciation and support (etc) are not fully present in all medical schools around the globe. The power of pathophysiology in dealing with complexities of human body reactivity has been accepted both by academia and clinical health providing system. They agree that pathophysiology brings a more profound understanding of patient’s condition. It remains just issue to fully implement the pathophysiological approach, institutionally and with the biomedical curricula.


bioenergetics and thermoregulation, etc). Such useful simplification imposes, however, a skewing attitude to consider the given problem as a “pure event”. Such skewing is present both in physician’s and scientist’s mind, as well. On the other side, in natural development of disease, various processes are very often combined with the elements belonging to the other classes of processes. Thus, disease processes, natural dynamics, regulation and outcomes (etc) as complex phenomenology seeks for a new frame of reference and methods to be used.

based algorhythmic analysis and re-synthesis. It turns out to be a student friendly and workable comprehensive method from teacher’s point of view. It has for steps.The first step isexposition of problem that gives short presentation of “raw data”. It is exposition of the problem based on patient records. It is primarily qualitative type of information in natural language of anamnesis and mixed with qualitative data of static and dynamic diagnostic information. The second step is the repetition of relevant knowledge. It is a multiple choice test, that includes statements related to the exposition and referred teaching materials. In the third step, the algorhythmic workout of the pathogenesis student builds-up the cause-consequence sequence of events out of given 25-30 units of etiopathogenesis. The task is to re-construct the etiopathogenetic pathways out of fragmented elements. He/she discovers a positive and negative feedback loops, and parallel and contextual events, as well. In the fourth step, student deals with systematization and quantitative aspects of the same problem. There is general tendency in natural development of diseases to form the common crossing points of reactivity. Etiopathogenetic pathways converge to the common units of pathogenesis. The heterogeneous types of diseases tend to group together, spontaneously, around certain etiopathogenetic element. Such common units are formed at certain deviation of electrolyte concentration (like hyponatreamia, hypophosphatemia, hyperchloremia, etc), macromolecular alterations (e.g., hypoproteinemia, dyslipidemias, etc), and than on cellular and organ functional levels (e.g., acute renal failure, seizures), as well. Such common “hubs“ of the response we named the etiopathogenetic clusters (EPC). We consider them as important integrators of natural pathophysiological processes. Such clusters integrate multiple inputs and multiple exits in the natural development of various diseases and altered conditions in human body. We think, the EPC may have both theoretical and practical importance in study of medical pathophysiology. The EPCs have tendency to form a network, with connecting pathways among them. Students find these approaches challenging and stimulative. Since all individual problems are written in “cases study“fashion, they find these methods to be challenging and important as introduction into the clinical reasoning. The matrix of given material leads the student through the clinical complexities and nonlinearity of pathophysiological responses within the real working-time framework. These strategies help students to organize medical knowledge and understanding and to reduce the information noise. The EPCs and algorhythms may be considered as teaching/ learning tool and a proper response to the challenging demands of contemporary medicine. Mentioned database of 32,000 diseases is reduced to the network of pathways of 91 EPC- points. The etiopathogenetic skeleton deals with branching points and connects local and systemic manifestations of underlying pathophysiology. EPC-networking seems to follow a self-directed natural propagation, spreading and pathways. Students’ surveys have graded these approaches 2.3 times better in comparison with classical methods of teaching/learning. The exam grading has shown the increasing curve-trends in dozens of student generations.

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PL3-Understanding cancer at the molecular level : From cancer genes to precision medicines and Biomarkers Florence Raynaud

PL4-Endnote address: Stress and Addiction: Pathophysiological Mechanisms Mustafa al’Absi Duluth Medical Research Institute (DMRI), University of Minnesota Medical School, 1035 University Drive Duluth, MN 5581, USA. Email: [email protected] Abstract: Stress is one of the most commonly reported precipitants of drug use and is considered the number one cause of maintenance of drug abuse and relapse. There have been a number of significant advances in research focusing on pathophysiological consequences of stress and addiction; along with this growth came the recognition of the importance of understanding the interaction of biological and psychosocial factors that influence risk for maintenance of addictive behaviors. In this presentation I will review work conducted in my laboratory focusing on the role of the hypothalamic-pituitaryadrenocortical (HPA) axis and the endogenous opioid system (EOS) in nicotine dependence. Nicotine acutely activates the HPA axis and the EOS system, and increased HPA activity has been linked to attenuated CNS nicotinic receptor sensitivity. I will present a series of studies demonstrating that steep decline in cortisol concentrations during early abstinence and hyporesponsiveness to stress predict significant mood deterioration, intense withdrawal symptoms, and early smoking relapse. Our recent results suggest that EOS dysregulation may play a role in these HPA response abnormalities in dependent smokers. Our studies also show that hormonal associations with smoking relapse tend to be more consistent in men, while intensity of withdrawal symptoms tends to be a consistent predictor of smoking relapse in women. Based on this research and work from other laboratories, we propose that dysregulation of HPA/EOS activity exacerbates withdrawal symptoms and may contribute to the maintaining drug use and relapse. Targeted investigation of treatment options involving these systems is timely. Our results also reinforce the need for gender-specific investigation of mechanistic and interventional strategies to combat addictive behaviors.

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Abstract: Cancer drug discovery is a multidisciplinary enterprise which succeeds when a suitable target is identified, the right compound is developed, and the clinical trial design is optimised. In the last decades, all these activities have substantially evolved as a result of novel technologies and computational tools. Our better understanding of the molecular events that drive malignancy together with the availability of databaseshelp us evaluate potential targets and decide which are the most ‘druggable’. Once the target has been validated, a screening assay and a test cascade are established to identify compounds that affect the target and have suitable pharmaceutical properties for administration to man. The iterative process of drug discovery and development is a team effort requiring a variety of expertise. The early development of assays to measure target engagement and inform the pharmacological audit trail are paramount to the successful development of novel agents. The effective implementation of biomarker assays in early clinical trials and the hypothesis driven tests of patient populations likely to benefit from novel therapies ensures rational and rapid development of novel agents.


Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, The Royal Marsden Hospital, Sutton, London, United Kingdom. Email: [email protected]

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SYMPOSIUM ABSTRACTS Symposium 1: Pathophysiology in medical education: Teaching and curricula

S1-1-35 years of pathophysiology undergraduate teaching in Portugal: a retrospective view looking at the future Nuno Neuparth

Abstract: A synthesis of pathophysiology undergraduate teaching will be described with emphasis on the curricular structure, the teaching and evaluation methods using PBL and concept maps.

S1-2-The integration of pathophysiology and evidence-based medicine in module based integrated curriculum Grigoryan Artem Department of Pathophysiology, Yerevan State Medical University, Armenia. Email: [email protected] Abstract: In many countries Pathophysiology is taught in the third year of study as a separate subject. Its main role is to provide a holistic approach to disease mechanisms and a synthetic view of morphological, biochemical, genetic, and clinical knowledge. Evidence based medicine (EBM) courses are also now taught during the first years of the study. Without specific integrative approach a contradiction may occur related to some key principles in EBM. For instance, according to the commonly cited Marchevsky, Critical Appraisal of Medical Literature, EBM aims to: de-emphasize intuition, unsystematic clinical experience, and pathophysiological rationale as sufficient grounds for clinical decision making. As a result, novice learner may be misguided in terms of proper algorithm for decision making. This becomes of special importance for young doctors attacked by pharmaceutical company representatives which are armored with randomized, blinded, and bias-free research data. EBM is not “cookbook” medicine: any external evidence should be carefully weighed, processed and individually applied. So, modifying Sackets approach we come to the formula EBM + pathophysiological processing + individual clinical expertise = proper decision making. One approach to train such skills in knowledge construction is the creation of specific modules in clinical pathophysiology where the students are given a relevant meta-analysis article or a RCT study as an object for problem based learning. The goal of the following analysis and discussion is the search for adequate possible pathophysiological explanations and mechanisms which are commonly neglected in the article. In such a way a naked medical fact becomes valuable and allows synthesis from heterogeneous data, which is a necessary step from EBM to personalized medicine.


Email: [email protected]

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Department of Pathophysiologv, Faculty of Medical, Sciences, New University of Lisbon, Portugal.

S1-3-Student research as an integration tool for teaching/learning process Navasardyan Grizelda Department of Pathophysiology, Yerevan State Medical University, Armenia. Email: [email protected] Abstract: 21st century requires new landmarks for higher medical education including change of role of higher institution: from knowledge-deliverer to knowledge-maker along with learners (students). Otherwise, there is a need of new academic culture in which student research is integrated into educational process. The vision of this concept is the following: teaching/learning should be reorganized in such way, that the learner acquires skills for research implementation and further direct participation in departments scientific research projects. The key for solution of this challenge is the integration of theoretical, experimental, clinical empiric knowledge with analytical-synthetic interpretations (horizontal, vertical and longitudinal integrations). The components of this process are: modeling of disease/pathological process (using experimental animals or computer simulation), creation of educational movies, preparation of morphological slides, chemical, biochemical, microbiological analysis, case studies, differential diagnosis, problem-based learning etc. The abovementioned is supplemented by literature review; where possible the student team-work is encouraged. Epidemiological data could direct the relevance of the research. The final results are discussed during round-table discussions or local conferences and after corresponding peer-review the findings are published in university press. Such approach also promotes student-centered learning, and improvement of higher medical education quality. This type of educational activities will move the university towards real research and science.

S1-4-Use of concept maps as an assessement tool in a Pathophysiology course António Bensabat Rendas, Teresa Gamboa, Nuno Neuparth NOVA Medical School, New University, Lisbon, Portugal. Email: [email protected] Abstract: In the context of a pathophysiology course to undergraduate medical students a comparison was made between standard MCQ tests and a concept map based test (CMBT). Results showed that CMBT is a feasible evaluation instrument to assess student performance in the above mentioned context.

Symposium 2: Pathophysiology and psychobiology of ion transport abnormalities and related disorders

S2-1-Na+i/K+i-mediated, Ca2+i-independent excitation-transcription coupling: physiological and pathophysiological implication Sergei N Orlov, Svetlana V Koltsova, Olga A Akimova, Johanne Tremblay, Pavel Hamet MV Lomonosov Moscow State University, Tomsk State University, Russia and Research Centre University of Montreal Hospital, Canada. Email: [email protected] Abstract: Data obtained during the last decade demonstrate the presence of novel Na+i/K+imediated, Ca2+i-independent signaling pathways involved in the regulation of gene transcription (Taurin et al., 2002; Haloui et al., 2007; Koltsova et al., 2012). Here, we present evidence thatthis

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novel mechanism of excitation-transcription coupling plays a key role in i) transcriptomic changes related to the memory formation and leaning process; ii) the functioning of skeletal muscle as an endocrine organ; iii) the pathogenesis of hypoxiaandischemic complication; iv) therapeutic actions cardiac glycosides. The forthcoming investigation should identify the molecular origin of upstream Na+i/K+I sensor and its targets in gene promoters.

Balanev Dmitry Abstract: The diagnostics of disorders of sensor-motor functions is very complicated and influenced with the fact that purposeful movement is a synergetic formation. The pathological changes of sensor-motor functions have physiological as well as psychological character. Taking this fact into consideration, we developed the variant of the method “speed-accuracy trade-off”. We additionally developed two independent variables, one of the variables presents the periodic sequence of stimulus tasks, and the second one is focused on the changes of the aim of task solving. Each of the variables has only two levels - it is the presence or absence of sequence, and the condition of solving the problem with the best results in the parameters of accuracy or time. In this case we didn’t change the conditions of management of traditionally used variables such as distance and size of the target. The time of task solving and accuracy of target choice, sequence and the character of changes are the dependent variables. The method works on a computer with a touch screen and is represented as a sequence of similar problems of choice of the circle center. We used a set of 60 tasks that participants had to solve as accurately as possible and then with the higher speed. There were more than two hundred participants who took part in the research. The results were evaluated with the help of traditional approach, frequency-response analysis and SVM. From the traditional point of view we were working at the problem of connection between the target distance, target size and time of task solving. The absence of this connection for the subject can be evaluated as the indicator of disturbance of sensor-motor functions. The approach that allows investigating of the peculiarities from the point of new introduced variables is more effective. We used data analysis to evaluate the sequence that was implemented with the Lomb-Scargle periodogram. The absence of the period in variation of dependent variable when it was influenced with independent variable is supposed to be the indicator that points out the possible problems that have physiological character. The evaluation of the results changes influenced with the change of aim of decision was done by defining the typological peculiarities of usage of the visualization method and support vector machine. We were able to find out five types of solving of tasks, the differences of each type can be explained from psychological point of view.


Tomsk State University, Tomsk, Russia. Email: [email protected]

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S2-2-Using of Tasks “speed-accuracy trade-off” to detect of disorders of senso-motor functions

S2-3-Features effect of recombinant interleukin 5 receptor on contractile responses of smooth muscles of the bronchi of guinea pigs sensitized with ovalbumin Kapilevich Leonid Tomsk State University, Tomsk, Russia. Email: [email protected] Abstract: In the present study, we investigated the effect of interleukin-5 (IL-5) and its receptor on the contractile activity of bronchial smooth muscle of guinea pigs. Contractile activity was studied using the mehanograf. Object of study is the ring segments main bronchi of guinea pigs. Epithelium was removed mechanically. Guinea pigs were sexually mature males. Strain amplitude was recalculated as a percentage of the amplitude of the test reduction by 40 mM KCl. Data analysis was performed using the rank U - Mann-Whitney test. IL-5 at concentrations of 1 pg/ ml and 0.01 micro g/ml did not change the tone of bronchial segments of its direct addition to the camera. Preincubation bronchial segments in RPMI-1640 medium supplemented with IL-5 (0.1 micro g/ml) led to an increase in the amplitude of contractile responses to histamine effects (10 and 100 micro M) (p