The sixth annual conference Cannabis and Science was held at the Brno Observatory and Planetarium. The purpose of the event is to evaluate the development of research and treatment with cannabis, education and news in this field. The conference was attended by 160 people from the ranks of doctors, biologists, researchers, scientists, students and patients.

Due to epidemiological conditions, one of the main speakers, Lumír Hanuš, a Czech chemist and scientist living in Israel. Despite this, the conference had a very busy programme. “On the agenda were topics ranging from basic research, i.e. the study of genetics, through the plant itself, cultivation, processing, the creation of medicinal preparations to clinical trials in our country and in the world. In the afternoon part, there was also experience from the perspective of doctors and patients,” said MVDr. Václav Trojan, Head of the Clinical Pharmacology Unit of the International Clinical Research Centre at St. Anne’s University Hospital in Brno (FNUSA-ICRC).

The conference originally started as an event of several enthusiasts who were involved in cannabis research. Now it has international participation, including professors from different disciplines. All agree that cannabis has a future. “Thanks to the changes that are taking place in the Czech legislation regarding cannabis, we are on the threshold of a period when we will move perhaps more steps in this area than in the past. This will help us to further intensify the connection between research and patients,” said FNUSA-ICRC Director Pavel Iványi.

St. Anne’s University Hospital in Brno is a leader in cannabis treatment in the Czech Republic. “We are currently treating 240 patients with cannabis for chronic pain of various origins, up from 220 last year. The biggest increase was recorded at the beginning of 2020, when it was decided that 90 percent of the prescribed medical cannabis would be covered by health insurance. Until then, there were only dozens of patients,” added the head of the FNUSA Pain Management Centre, Radovan Hřib, MD, who is also involved in cannabis research at the FNUSA International Clinical Research Centre.

“In the last two years we have achieved many things, such as the establishment of the Cannabis Research Centre or the commissioning of a cannabis cultivation facility for research. I am delighted to be part of a journey that starts with genetic information and ends with the patient. I am proud and grateful that we can develop something like this in this combination and I dare say we are the only ones in the world. At St. Anne’s University Hospital in Brno we have scientists, doctors and patients in one place, which is really unique,” added Václav Trojan.

cannabis and science

Cardiovascular magnetic resonance imaging is one of the most advanced non-invasive methods of obtaining information about the heart and its function. One of the methods used is T1 mapping, which allows to measure the extracellular (interstitial) volume of the heart muscle, as one of the important markers of cardiovascular diseases.

T1 mapping uses measured T1 relaxation time values obtained before and after administration of a gadolinium contrast agent. However, the hematocrit value, which is the proportion of red blood cells to total blood volume, is also important for accurate calculation. In the study, researchers from the Cardiovascular Magnetic Resonance team at the International Clinical Research Centre at St. Anne’s University Hospital Brno and the I. IKAK of St. Anne’s University Hospital Brno focused on determining it using values obtained directly during T1 mapping. This method greatly simplifies the whole procedure and is already used in some centres, but a comprehensive overview of calculation methods has not been published yet. In addition to determining the best method of calculation, the researchers also attempted to further refine the formula by adding the values obtained after the application of the contrast agent.

For this purpose, they used values obtained by measuring 139 patients. “We first measured hematocrit values using standard laboratory techniques, then used cardiovascular magnetic resonance to determine the T1 relaxation times of the blood before and after contrast agent administration and used statistical methods to determine the relationship between these values. Subsequently, we investigated the accuracy of the calculation with each type of formula using conventional formulas, calibrated statistically for our department and then adding post-contrast values,” said Dr. Lukáš Opatřil.

In the end, the reciprocal model of the formula calibrated for the workplace proved to be the most accurate and the addition of post-contrast values further improved its accuracy significantly. “Using this calculation could unify and refine this time- and cost-efficient method in the future,” said Dr Opatřil.

The final formula and the full study can be found here:

OpatrilCMR measurement

The Large Research Infrastructure CZECRIN was created based on close cooperation between Masaryk University, and the International Clinical Research Centre of the University Hospital at St. Anny in Brno passed the international evaluation of research infrastructures with the total number of points.

The Large Research Infrastructure CZECRIN, which supports academic clinical trials and connects university hospitals, universities, and research centers in the field of biomedicine, has achieved an excellent evaluation in the last international evaluation of research infrastructures in the Czech Republic, announced and coordinated by the Ministry of Education. CZECRIN thus received recommendations for financing in the coming years. “We are particularly pleased that we have defended the highest possible evaluation from the previous 2018 evaluations. Since then, we have not only maintained a high level of infrastructure but have also significantly developed its activities,” adds Lenka Součková, national infrastructure coordinator and assistant professor at the Institute of Pharmacology, Faculty of Medicine, Masaryk University.

Since the last evaluation, after which the infrastructure also became a full member of the European ECRIN network (status valid since 2018), CZECRIN has expanded its expertise, thus expanding the areas of support for medical facilities and research. CZECRIN offers its members comprehensive support in the field of clinical research in all its phases. An All-In-One scheme provides researchers with consultation, management, and coordination of clinical trials, regulatory expertise, pharmacoeconomic studies and offers research access to a unique certified GMP unit for research and development of advanced therapy medicinal products (ATMP).

The infrastructure has also given rise to industry-oriented networks to facilitate cooperation in individual research areas (e.g., STROCZECH – Czech Stroke Research Network, CZECRIN ONCO) and is constantly expanding its reach and support. “It is a unique connection between researchers-physicians and the already existing research network, which helps them to implement their ideas for the implementation of academic clinical studies. Industry-oriented networks reflect leading research areas in medicine, and thanks to involvement in CZECRIN, it is possible to verify directly and subsequently apply innovations to patient care.” explains doc. MUDr. Regina Demlova, Ph.D., director of Infrastructure and Head of the Institute of Pharmacology, Faculty of Medicine, Masaryk University.

This year, CZECRIN is part of 92 national and 22 international projects focused on clinical research to optimize human health care.

The second highest civilian award, the Order of the Italian Star, was awarded to an Italian scientist Giancarlo Forte this June. He received the award in recognition of his work and for representing Italy abroad. He is the head of the Center for Translational Medicine at the International Center for Clinical Research of the St. Anne’s University Hospital in Brno (FNUSA-ICRC), which he has built and has been working there for more than 8 years. In the past, he also lived and worked in Japan and Germany, but since 2013 he has been living with his wife in Brno, where their daughter was born in 2017.

When it comes to his research, he studies cardiovascular diseases, diseases of the brain and nervous system, immune system diseases and selected types of cancer. As a part of his research, he also works with stem cells that can regenerate tissues and thus represent a potential for the treatment of many diseases.

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Was becoming a scientist always your dream, or did you have another career in mind?

When I was a kid, I wanted to become an archeologist. Because I had this dream of becoming Indiana Jones, but then with time, I developed an interest in natural sciences and biology. My decision to become a scientist was made in high school.

Previously you worked and lived abroad, why did you choose specifically Germany and Japan?

Usually, in science, you don’t choose that much as far as location is concerned because of the projects. Whenever you are working on a specific scientific project, you make sure that you choose the best place where this can be pursued. So Germany came as an offer after my Graduation, and I was interested in the offered project. So I decided to move there. With Japan, it was similar, but in that case, one of my mentors of the Ph.D. moved to japan, and he invited me to join for a while. During that period, I met a japanese professor who invited me to apply for a position, and that’s how I got the job in Japan. Moving around is basically driven by science and the specific programs that each place focuses on.

Were you always planning to work or live abroad?

No, I always had this idea of being a globetrotter, and I wanted to actually move abroad for a period of time. I just didn’t know how long this period would be. And then with science, you are told constantly that you should go to the best lab or to follow the project you are working on. And then it became natural. It’s kind of a natural part of the life of all scientists.

Out of all the places in the world, why did you choose Brno?

This was pure chance. Basically, after a few years in Japan, I decided I wanted to go back to Europe because of the earthquake, nuclear fallout, and tsunami. Those are the moments when you realize how far you are from Home. I started to look for a position, and then I found a possible position in this brand-new institute in Brno, and I simply took the challenge. I visited Brno, and I liked it immediately, so together with my wife, we decided that it was a good place to start fresh.

How different is Brno from other places where you have worked? Or is it the same everywhere?

No, it’s not the same everywhere. It’s completely the opposite of Japan. Since being in Japan feels like living upside down, Brno feels like going back to normality. European lifestyle is somehow homogenous, more homogenous than living in the far east or in the USA, so Brno is very close to our lifestyle. I think I just experienced the language shock, I was quite used to the European lifestyle, and Brno is quite a European city.

Is there something in Italy you miss now that you live in Brno?

We miss our family and friends. When you move around, you somehow feel closer to long-term friends. As we travel and move abroad, we are actually driven to value friendship and family more. Apart from that I also miss the weather and the food, but that’s something you can live with.

What does the award mean for those who receive it? And What does it mean to you specifically?

The award is a commendation by the president of the Italian republic, which is given to Italians but sometimes also foreigners who help represent the nation abroad. Even Though it is an old status, I was happy to see that probably for the first time, it was awarded to a scientist. Usually, most young italian scientists are forced to go abroad because there are no possibilities to work at home. I don’t think it’s bad, I decided to go on my own, and I never felt exiled. But for all Italian scientists who are abroad, it’s nice to hear that the president values our contribution even though we are not giving it directly to the country, but we are giving it to the country from abroad. So in my case, I felt that it was an appreciation of the work we have been doing. And it’s not just about me. It’s about the whole lab and the whole FNUSA-ICRC and what we have been doing to create an international environment and to make all the students and scientists who are traveling the world feel comfortable and like they are at home. We have many nationalities in the lab, and people are, as far as I know, happy to be there. We give them a chance, train them, and make sure they feel welcome.

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What does your research focus on?

I specifically coordinate the center for translational medicine within the FNUSA-ICRC, where we do translational research. So we study and investigate the molecular basis of diseases affecting the cardiovascular system, diseases of the nervous system (brain and nervous system), diseases of the immune system, and some selected kinds of cancer. We basically try to bridge the clinical experience of the pathology itself, of the symptoms with the causes at the cell and tissue level.

What are your research plans or goals for the future, and are you planning to stay in Brno?

During these years, we have made some interesting contributions and discoveries about new possible mechanisms of pathologies both in cancer and in cardiovascular diseases, so we would like to investigate this further. The challenge here is to turn our knowledge of the mechanisms of disease into a cure. We would be happy to move a little closer to the clinics and the patients and try to understand how we can control these molecular processes to design some potential treatments. Obviously, I am dreaming here because the path to the clinics is very far for everybody, and it is clear to everybody that the path from translational science to the design of disease treatment is a very long one.

When it comes to moving abroad, that depends on many circumstances. It’s also true that scientists are globetrotters, and sooner or later, they need to find a new place. It’s possible that in the future, we will look for new challenges somewhere else, but for the time being, we are happy in Brno. We are happy with the possibilities we have to do research and express ourselves as scientists, and there is currently no plan we have for the far future.

Do you have any wild dreams or plans you have when it comes to research?

Most of the science is incremental. We try to take little steps in one direction, which are fueled not only by curiosity but also by the support of other colleagues. This knowledge builds up, and then, in the end, you reach something revolutionary, but most of the efforts are incremental. I definitely don’t plan a revolution. Revolutions in science are usually random, so they come just by chance.

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Protein Engineering team at International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC) and Faculty of Science of Masaryk University has focused on the potential of web-based screening tools in accelerating the discovery of cancer-treating drugs based on microbial products. Protein Engineering team have presented a review of web screening tools, such as molecular databases, and provided a step-by-step description of how to use them. “Our goal is to increase awareness of available virtual screening tools within the medical and scientific community, particularly among those working in experimental and clinical oncology,” explained head of the team Jiří Damborský. There are multiple methods and the use of each depends on the available information we have about the microbial products and the molecules being targeted.

At the moment, cancer can be treated by chemo, radiotherapy, surgery, RNA-binding proteins, targeted therapy, or immunotherapy which uses microbial products. Microbial products, such as cellular components or viral particles, are used to target and inhibit proteins involved in carcinogenesis and present a relatively low-cost method to treat cancer. However, there are many different microbial products that could be used and many different proteins that need to be targeted. That is why virtual screening tools are essential in making the process of finding potential anti-cancer drugs more efficient, as they predict how specific molecules will react with one another and thus show us which combinations are most promising.

Overall, the use of virtual screening tools presents an available and low-cost way to speed up the discovery and development of anti-cancer drugs while also enriching the online databases of compounds that could be tested in the future. “However, it is essential to keep in mind that using automated web tools brings challenges of its own, and, for most computational methods, the results will only be as good as the input data,” concluded the head of Bioinformatics unit David Bednář.

The full review is available here

David-Bednar

The blood of many animals, including humans, contains about 40% red blood cells, which bind oxygen but also impede blood flow in the blood vessels. Mathematical models suggest that 40% is optimal. It provides the highest oxygen supply to the tissues. Nature has arrived at it through evolution. However, previous theories have not explained why elite athletes perform better after (illegal) blood transfusions or erythropoietin, nor why there are animals, such as dogs and horses, that expel concentrated blood from the spleen during physical exercise. In both cases the resulting haematocrit is higher than the optimal 40%.

“Together with Dr. Stark and Prof. Schuster from the Friedrich Schiller University in Jena, Germany, we studied the optimal percentage of red blood cells in the blood (the so-called hematocrit) during extreme physical exertion limited by cardiac performance,” said Michal Šitina, M.D., head of the Biostatistics research team at the International Clinical Research Centre of St. Anne’s University Hospital in Brno.

“In our study, we mathematically described the blood oxygen supply to tissues both under resting conditions without cardiac restriction and under conditions of extreme physical exercise, when blood flow is restricted by maximal cardiac output,” described Šitina. The calculation showed that under resting conditions, the optimal hematocrit value is indeed 40%, but it rises to 60% during physical exercise. This is the value observed in horses just after a race. This work thus explained the observed findings and refined the theory of the optimal haematocrit. Limiting cardiac performance, however, even without major physical exertion, are patients with severe heart failure. “In the next theoretical study, we would like to calculate the optimal hematocrit value for just such patients,” said Šitina

The article is available here:

Michal-Šitina

The Kardiovize team from the International Clinical Research Centre of St. Anne’s University Hospital in Brno has prepared preventive examinations for the public, aimed at the possible detection of cardiometabolic diseases. Interested people will undergo a medical examination by a doctor, a sonograph or a nutritional counsellor.

Preventive check-ups – especially for cardiometabolic diseases – are very important. “According to the results of our Kardiovize study, approximately 60% of the adult population in Brno meets the criteria for starting lifestyle intervention programmes at an early stage of the disease. Our centre can contribute to the detection and stratification of at-risk subjects and provide effective interventions. Currently, the Kardiovize Lifestyle Centre offers screening and lifestyle interventions as part of primary prevention (i.e. before the onset of any complication). Effective interventions in the early stages of the disease prevent the development of complications and are especially designed for people who are overweight – obesity, prediabetes, hypertension, dyslipidemia, type 2 diabetes – but without the presence of complications (stroke, heart attack, etc.),” said Juan Pablo Gonzalez Rivas, head of the Kardiovize research team, adding: “Unhealthy lifestyles are the cause of most common diseases worldwide. Unhealthy diet, lack of physical activity, tobacco use and excessive alcohol consumption are the main drivers of non-communicable diseases. Lifestyle medicine offers an opportunity to prevent these diseases and complications in their early stages.”

Kardiovize is offering three packages to interested parties based on the number of tests and collections. This is a paid service. For more information, interested parties can visit the website at www.fnusa-icrc.org or contact Kardiovize experts directly at 549 185 592, 603 299 683 or email infokardiovize@fnusa.cz.

Kardiovize

Mgr. Martin Toul, a member of the Protein Engineering team at International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), won the poster of the day award at the 45th Congress of the Federation of European Biochemical Societies (FEBS). In addition, he also won the Outstanding poster of FEBS Open Bio Editor prize, which was given to only 4 out of a total of 1285 participants. The poster was titled “Engineering protein dynamics for the understanding of the divergent evolution of the Renilla luciferase” and described research on the role of protein dynamics and their high efficiency to understand the evolution of luciferase in Sea pansy (Renilla reniformis) on a molecular level.

Luciferase is the name of enzymes that allow animals to produce light (bioluminescence). The best-known example of an animal using bioluminescence is a firefly. The light is produced as a result of an oxidation reaction of a luciferin molecule in the presence of the enzyme luciferase. The range of bioluminescence colors is relatively extensive, ranging from blue-violet, found mainly in marine organisms including the sea pansy Renilla, to red, which can be seen on the beaches of California during so-called “red tides.”

Luciferase is beneficial not only for organisms in nature but also for laboratory use. It serves as an imaging technique for processes in living organisms, such as insulin secretion imaging. It can also monitor genes, their expression, or their interaction with other biomolecules. Luciferase is also used to monitor the spreading of labeled viruses or cancer cells. Using dynamics engineering of luciferase, Toul, in collaboration with other colleagues from the research team, constructed a new type of luciferase with a 100 times prolonged bioluminescence compared to the original short flash.

 

“The result is of great importance wherever the enzyme luciferase is used as a diagnostic system for monitoring gene expression or as an imaging technique. The prolongation of bioluminescence can extend the practical application of luciferase even more and make it more efficient, as the original short flash luminescence was not suitable for long-term monitoring of a stable bioluminescence signal. The newly modified protein makes this possible, “concluded Toul.

Martin-Toul

When it comes to evaluating myocardial deformations (strains), cardiovascular magnetic resonance (CMR) imaging is a widely used tool and offers a number of techniques for this purpose. The method of tagging is considered to be the gold standard for the evaluation of myocardial strain using CMR. But due to its specific requirements (need to scan additional sequences), this technique is used relatively little. On the other hand, CMR feature tracking (FT), a new imaging technique, is more practical and beneficial in clinical settings, but the verification of measurement accuracy is limited. The comparison of different methods of measuring myocardial deformation and comparison of used software is what the research in collaboration with doc. MUDr. Roman Panovský, Ph.D., the head of the Cardiovascular Magnetic Resonance Research Team at International Clinical Research Center of St. Anne’s University Hospital Brno (FNUSA-ICRC), focused on.

The research involved 61 participants, of which 18 were healthy, and 43 had heart conditions such as chronic heart attack, dilated cardiomyopathy, or left ventricular hypertrophy. For all participants, different dimensions of myocardial strains were measured. The measurements included global and regional longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). All measurements were performed using 3 different post-processing software, and the measured values were compared within individual techniques and against tagging.

While the global LS and global CS data among software and tagging were similarly accurate, significant differences were seen for global RS and all strain dimensions on a regional level. “The reliability of global strain measurement for longitudinal and circumferential strains is important information for the introduction of the FT method into routine clinical practice. On the contrary, due to the significant variability of regional strains, it is not possible to recommend this evaluation for the purpose of drawing clinical conclusions,” stated associate professor Panovský.

The full research can be found here.

 

Dedication
Panovsky

The St. Anne’s University Hospital Brno has launched a trial run of its own experimental cannabis cultivation facility. It has become the first medical facility in the Czech Republic to grow medicinal cannabis. For the time being for research purposes.

St. Anne’s University Hospital Brno (FNUSA) is the leading Czech institution in the development and use of medical cannabis treatment. “We use it at our department for pain treatment. It also has indications for the treatment of many problems in other medical fields. In general, cannabis treatment raises a number of unanswered questions, yet it meets the requirements for high safety breadth. For further development of treatment and understanding of the effects, we want to follow up the clinical practice with research,” said Radovan Hřib, MD, Head of the Pain Management Centre of the Anaesthesiology and Resuscitation Clinic of FNUSA and the Faculty of Medicine MU, and added: “The cultivation facility will allow us to have our own, precisely defined material for pharmacological, preclinical or other clinical research without additional huge costs. This includes, for example, new therapeutic forms such as extraction tailored to the patient, the development of other medical varieties of medicinal cannabis, modern forms of drugs with, for example, nanoparticles, etc.”

“Our hospital was the first state medical facility in the Czech Republic to start using medical cannabis. For the first time ever, we also introduced its use in capsules, which are produced by our pharmacy. The cultivation and research is therefore the logical next step,” said the director of St. Anne’s University Hospital Brno Ing. Vlastimil Vajdák. “We hope that in the foreseeable future, with the change of legislation in the Czech Republic, we will be able to use the grown products not only for science and research, but also as medicines. The effort to link the scientific, medical and business strategies of FNUSA and FNUSA-ICRC is one of our strategic goals and the way we want to go,” added Pavel Iványi MBA, LLM, Executive Director of the International Clinical Research Centre of St. Anne’s University Hospital Brno (FNUSA-ICRC).

The combination of clinical and research at FNUSA is ideal thanks to its International Clinical Research Centre. “Connecting our own research cultivation facility to the teams at our research centre brings countless research opportunities literally under one roof. This connection and the guarantee of standardised material for our own research, in addition to the possibility of applying the results in practice, i.e. with patients, is even unique in the world,” emphasised MVDr. Václav Trojan, Ph.D., Head of the Clinical Pharmacology Unit of the International Clinical Research Centre of FNUSA.

The hospital already has a special permit to handle plants with high THC content. The cultivation plant is now in trial operation. “The cannabis grown must be of pharmaceutical quality. For example, there must be no introduction of infection from outside. Workers must observe strict hygiene measures, the possibility of pathogens being transferred from clothing or hands is a major risk. This is one of the reasons why only a very limited number of people have access to the growing areas,” explained Václav Trojan, adding that it goes without saying that no pesticides or other substances are used to promote plant growth or yield. “We have chosen a basalt wool growing system with drip irrigation control. There is also precise monitoring and control of all external factors – light, heat or humidity. We will be able to fully control and monitor the growing equipment online and remotely.”

The actual operation of the grow room is one part of the cannabis research. Scientists will investigate the effects of external conditions on the growth of the plants or the actual production of content in the inflorescence. “The extract obtained is actually a mixture of active substances from the cannabis plant. Some of them like THC have detailed effects. But what about the others? Scientists are working hard to isolate the substances and study them separately. For example, CBD cannabidiol is of great interest for its regenerative properties after exertion. Research into the preclinical part, i.e. the possibility of processing the flower for other forms of application, will also be carried out in the pharmacy areas of our clinical pharmacology unit. There are a number of methods of extracting the contents – mechanical, by organic solvents or through carbon dioxide. The extract obtained is the basis for the preparation of creams or suppositories, for example. There are many possibilities, and our research will be able to map everything thoroughly thanks to the cultivation facility,” summarises scientist Václav Trojan.

The substances extracted from cannabis, or mixtures thereof, will be tested first on cell cultures by scientists from the International Clinical Research Centre at St. Anne’s University Hospital. “The road to a clinical trial is very long for substances that are expected to become medicines. For dietary supplements, which include CBD cannabidiol, for example, it is easier. That’s why a clinical trial with CBD substances and CBD nano-forms will take place this autumn. It involves monitoring one parameter in 30 volunteers. The whole process from the preparation for the study to its completion takes a year,” added Václav Trojan. “The main goal of the whole research is the development of cannabis treatment. It has many unexplored areas and so far also many poorly scientifically based promising results. The most elaborated is the treatment of pain, but the use in neurology or dermatology also seems very promising. The question of research is definitely not a question for one “summer season” but a comprehensive development of the whole scientific discipline on the cannabis plant,” added Radovan Hřib.

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