[Music] good evening good afternoon good morning ladies and gentlemen wherever you are welcome to our new live webinar on fictional I should say on your TV program so fictional dot online as often as possible we have the opportunity to address questions from the from your concern from the practical issue up to the scientific basis and by the way do not hesitate to suggest new topics such we should address in the coming weeks and months today we will address a link between oxidative stress inflammation and immunity quite a complex issue but you will see with the people around the table we have quite a lot of debates around as each webinar we start with a first part to introduce to set up the frame of the topics and to give the basis to allow you to ask questions during the round table time so you will see at any time you can ask your questions do not forget also to visit your fictional site your fictional dot online site you will have the pleasure in fact to look at the video of the plenary reviews recorded at ESPN in Gdansk in Poland last June as well as a video of poultry or swine and a ruminant conference we organized in October and November this year you will also have access to two advance' we organised one in April in Roma along the gut digestives Ergotelis conference on butyrate from nutrient to messenger and another one who organized ink dance on viability the nutritionists nightmare it is our AIDS free channel live webinar today and we are pleased to welcome lots of participants I just remind you that you can post your questions at fictional dot feature under dot online at any time during the presentation we will try to answer out all question and if not it will be answered on the site [Music] we are often challenged by several issues on the same topic for instance when we talk about in unity information oxidative stress it can be correlated related and so on but sometime for when you are at the end of the chain you don't know how to deal with that so it will be the objective today to try to find and to illustrate a link between all these aspects and I'm pleased to welcome around the table quite very well-known expert in the field of oxidative stress immunity and inflammation priority to the lady so professor shallow klauridsen the head of hello head of immunology and microbiology department of animal science at a university in denmark we know with long expertise on vitamin E and I would say now vitamin E and selenium in swine professor van Casper's hello professor for animal physiology Faculty of Veterinary Medicine in University of Munich in Germany and I would say co-leader of the Munich avian immunology group quite an interesting group and expert on development and immune system and if you remember so talk down in Dubrovnik during the EPC it was very exciting to see how microbiota is influencing the immune development and professor Peters you're a well-known expert on antioxidants and in selenium director of an innovative small company feed food limited also professor of nutritional biochemistry and I think it's interesting to see nutritional biochemistry at the College of Agriculture in near Glasgow in air in Scotland and it should say maybe shortly independent country in Europe and lots of honorary professorship from Ukraine Albania Gary and more as you can see around the table quite a lot of experts and a lot of brains and I'm sure that it will bring a lot of questions and a lot of potential and so on and discussion I would like to start today there will be not by city comes a frame and Petrea asking burnt how to define the immune system and the particle is a good immune system yeah thank you will be pleasure to discuss it briefly it's a complex system su as you mentioned before but basically what we should keep in mind is that we have the lumen with a whole lot of microbiota bacteria in there and also the nutrient factors then this is separated from the rest of the body by just a single layer of epithelial cells covered by mucous and underneath we have a huge number of immune cells and the histology picture here shows you just the macrophages in the gut so we should consider the whole system as also being a very dynamic system not static but the cells can move they can move from the blood into the mucosal tissues but they also move from the mucosal tissues back into the lymph vessels and into the blood and thus communicate what is going on in the gut to the rest of the body so it is if we think about it a complex system where we have to consider that the first issue for the gut immune system is to maintain homeostasis so to maintain a balanced system and not to overreact to just the common challenges the other hand if a pathogen comes in the immune system has to be there and has to be an alert and respond quickly and these responses lead to inflammation as we will discuss later also after an inflammatory response has been initiated it's the the job of the immune system basically to turn it down again back to homeostatic conditions otherwise we would get chronic inflammation and chronic inflammation definitely is a major problem and we don't want to see that so if we look at the immune system and if we want to investigate the immune system we really have to consider investigating the microbiota their function their metabolites also nutrient nutrient factors we have to consider the interaction between these factors and the epithelial cells and then also between these factors and the immune cells and between epithelial cells and immune cells so highly complex system but we are making step by step a little bit of progress to understand it so that's the first part on the immune system patter is a good immune system how now to define inflammation and maybe shallots start to set up the frame on the inflammation and what to how to trigger information in fact I think we all aware that if we get a skin injury some of the symptoms of inflammation is actually the redness of the skin heat the pain and the swollen skin and then we can easily imagine that some of the same mechanisms are taking place in the gut so when the pathogens are meeting will the immune cells here in this illustration and the macrophages they will start to engulf these pathogens and then initiate an inflammatory response and that will actually create some of the same as signs in the gut epithelium and it is very important that everything is now taking place like the secretion of the chemokines and cytokines in order to induce these inflammatory reactions however the problem is still that they need to be tightly controlled and to complement that bent Anzio but is secreted by you know the immune system immune cells and so on yeah we discussed it already a lot of inflammatory mediators first of all a number of cytokines and chemokines so in general of the pathogen is coming in then also products of the pathogen are detected by the immune system and those we call them collectively a pathogen associated molecular patterns or microbe associated molecular patterns they are detected by the cells of the immune system and then those cells start to respond by secreting inflammatory cytokines in particular the macrophages do that and here's a list showing some of them like interleukin 1 into looking six too many crosses factor alpha in the number of chemokines and chemokines are particularly important because they are able to attract new cells into the tissue from the blood and thus attracting cells which can help to control the pathogen and the spread of the path of change and on the right hand side in this slide you can see an example someone ally infection and a chicken and the induction of a particular chemo kind called CCL 16 which is induced very rapidly after infection can help to attract cells into the tissue and you can see it's expressed as long as a infection earth there and then this particular experiment was for roughly 50 days but then it's turned down this is again a very important issue which I would like to stress that at the end of such a infection the immune system has to be turned back to balance yeah and we can see that on the next slide and addressing yes yeah that there are also some factors produced by cells of the immune system which can tip the balance back to homeostasis and into leveled field such as interleukin 10 or tumor necrosis factor-alpha that is important that's an important factor talking about balance and we will talk after about redox balance but I think it's very important to have in mind that in any system we need to be responsive to a challenge but also to come back to Miss disease to a balanced situation if we go on the inflammatory response and the response of the element when there is bacterial contamination of the battery aggression and so on how it works with the immune cells a macrophage and so on Charlotte yeah actually now we have talked a lot about the reactions during the psycho psychosis but let's talk a little bit more about how do the immune cells actually kill these invading pathogens and the way they do this is that a lot of reactive oxygen species are being produced and they are very toxic they are very aggressive and but they are also very important and it's actually the same way or it is hypothesized that anti microbials is actually also working in the same way killing bacteria but if I had that mechanism but of course when this is taking pain place we have the so-called respiratory burst and this is again when we talk about that and that these reactive oxygen species and and you can see on this slide here that for instance hydrogen peroxides and all those pieces that generated by the enzymes in the cytosol so again a bottom line is that the rush production is very important in order to do the job killing bacteria but if we do not control this it can be very dangerous for the gut epithelium and this is why we need the antioxidants in order to protect the so we see because now the link between oxidative stress and inflammation and immune response and if we go a bit deeper on the oxidative stress Peter what is the action on the of the oxidative stress on the different component of immunity yes indeed free radical production by a phagocyte cell is a very important physiological process for them this is a weapon which is used to kill pathogens however the excess of production of free radicals or deficiency of antioxidants can cause oxidative stress and oxidative stress is considered to be the major detrimental for major parts of the immune system we are talking about fiber side function compromised compromised antibody production decreased activity natural killer cells and most importantly it seems likely that free radicals can actually damage the communication between different types of immune cells therefore the immune cell immune system management it will be broken and it's a major problem as I see today and we need to remember that there is a very delicate balance between antioxidants and pro-oxidant for example the field there is a plenty of various and talks and compounds but on the other side there are also proxy dance likes oxidized fat mycotoxins and many others therefore this is a very important balance which determine redox potential of the God and redox potential of major cells in the body and depending on which part of the balances goes down we are talking about maintaining redox potential and good health and good immunity or alternatively we are talking about oxidative stress and as a consequence the compromised immunity so against an important aspect his balance is really balanced on the antioxidant proxy dance as well balance on the immune system what are the players of the antioxidant system yeah helping in all disease research for the last 40 years and in this slide what I would like to show that every antioxidant in the board has its own role to play but all of them are built in a team which we call the antioxidant system and the vitamin E I called headquarter and talks in defense carotenoids communicate in services or antiox in defense flavonoids are antioxidant police and you can see there are more than 800 to this group we also have vitamin C which we called Special Forces but here most important one what we are talking about is selenium which I called chief executive on torques and defense and hopefully in fuel next slide I would explain why I put selenium in here are here wool and toxins so high so it's important to consider that these are a lot of antioxidants but particularly focusing on on selenium what is the role of selenium in the mechanism well recently we celebrated 200 years in selenium discovery and today what we know that there are at least 25 cellular proteins in the chicken in Peaks and in other farm animals and all those cellular proteins are important plays in maintaining of Antioch sand defense and maintained in redox balance and therefore we have selenium which is coming from feed ingredients as well as from feed supplements then from all forms of selenium specific element called Sulli not cysteine is synthesized and Celino at cysteine is a major part of the active center of those 25 Salina proteins and those set in the proteins as I mentioned I enrolled in an talks and defense maintenance redox balance maintenance maintaining cell signaling and eventually providing protection against oxidative stress and generally speaking if we look at that all those 25 cellular proteins the more than half of them are involved in antioxidant defense the redox balance and signaling therefore this is a major role of silina proteins to maintain redox balance and redox marbles maintenance will affect practically all parts of the body including immune system so now when we have now setups oxidative stress a set of the immune systems the information what is a link between selenium inflammation and immunity and and regarding the cellular protein first finds on Jupiter yeah if we look at the effect of zosyn in the protein on animal health we we can talk about reproduction we can talk about growth and development but for our today's topic the effect of those selena proteins on the maintenance of immune system is most most important one and coming back to the slide which I showed you previously when selenium deficiency or oxidative stress actually destroys the communication between various part of the immune system which affect most of immune cells therefore by using optimal dose is an optimal form of selenium we will help to those cellular proteins to be expressed to miss a maximum effect a maximum extent and by doing this one the antioxidant protection will be maximum redox potential will be maintained and this will help to maintain in Ana competence and if we look at the literature data or on this one you can see on these slides that we are talking about effect of selenium on various immune cells some of them like B lymphocyte T lymphocytes and macrophages and hetero fields there is plenty of data to show the effect of selenium as is less data but still most of immuno cells are affected by selenium status now we look at all these aspects and so on and particularly as the connection with immunity how the oxidative stress can interfere with the immune response band yeah well obviously there are a number of components which are directly affected as we've seen particular cell types but the other thing is that the immune system is a highly integrated system so cells very closely communicate with each other and they actually control each other and regulate each other good example is the interaction between the T helper cell and the B lymphocyte so without T cell help we will never ever get a good B cell antibody response as shown here but also the interaction between key lymphocytes and antigen presenting cells and so on and so on and so if oxidative stress would impact on a particular cell type it will always also impact on other cells of the immune system and this highly complex interacting so it's interesting because we talked about balance we talked about communication so it's a another way to be due to involve the different aspects when we look at the different inducer of the inflammation response and the mechanism may be shallow you can illustrate a little bit more on the different type of stress we can have yeah I think I would like to give an example on what can actually induce oxidative stress and inflammatory reactions in the gut and by mentioning the small piglets while it's suckling the South there is the commensal microbiota everything is fine and so on but they immediately when it's weaned from the south and not only social stressors but a lot of other things factors which can actually induce inflammatory actions and oxidative stress and these are mentioned here and you can easily imagine going from milk to solid feeds you can imagine the pathogens the new pathogens which is now in the environment where the small pigment will go and overall very soon this may be dysbiosis which is created during the weaning period and also inflammatory reactions created just due to the weaning will actually induce all these reactions we have just talked about and I think overall there is this induction of NF kappa-b and I think it's small from apparently bent you can explain you can be posed amusing the question is how does it work on a molecular level and immunologists have looked into that for a long long time and one of the first transcription factors with major relevance identify was NF kappa-b there's no clear fact that Kappa B so when there is an inflammatory stimulus the stimulated immune cell will activate the NF kappa-b system in such a way that NF kappab we will be translocated to the nucleus as you can see here and then induced transcription of inflammatory genes and these are again those which we mentioned before the matura cytokines and chemokines interleukin 1 and 2 looking 16 fl for interleukin 8 and through this mechanism the inflammatory response is initiated and started question is how does the entire oxidative system gets involved in this and antioxidative mechanisms may actually regulate that so now we go deeper on the mechanism so what is the role of selenium in that mechanism points on sir peter well here we again talking about balance we are talking about balance between two different they are playing two very various transcription factors but here two major one one is was mentioned already NF kappa-b which is responsible for actually activations of genes responsible for synthesis of pro-inflammatory cytokines and there is another transcription factor called an RF 2 which is responsible for antioxidant system maintenance in fact it activates more than 200 different antioxidant molecules to be synthesized and by activating them they produce extra antioxidants and they maintain antioxidant system which is extremely important for immunity therefore when we are talking about selenium we are talking about effect again on one side of the bar when we talking about optimal form and level of silly humans a diet 25 cellular protein synthesized and those versed in the proteins are maintained in redox balance which eventually will be involved in maintenance or interaction system on the other side this optimal redox violence will actually maintain under the control NF kappa-b not to be over - not to increase evolve a product of cytokines pro-inflammatory cytokines or maintained antioxidant system therefore in this balance selenium is a key player because of that specific role in maintaining redox balance they make a good transition Peter because we talked about stress or like pathogen we talk about diet imbalance mycotoxin winning for instance and so on but even during the normal life I would say our very highly positive annual there is something some issues regarding oxidative stress are not on this slide we have actually indicated that just breathing towards high performing high producing animals can actually increase the risk of oxidative stress so this is not only that the production cycle of brightest has really been shortened but also like if you take the the pigs that if you measure now what is the level of oxidative stress in the plots you'd maybe find that it is as high as in human after the human has actually been running and all Samaritan just imagine that I already mentioned some risks of oxidative stress but add-on should actually be that well will our intensive production of animals they may actually be at a higher risk of oxidative stress than at least you know the rule once it's very interesting what you say because I often say to when I talk to and friends you know to say we are feeding managing in fact athletes you know it's very high producing there is very high producing sounds high producing broilers and so on so we are really dealing with very very special animals in fact it's actually not we're all ones and so on so I think it's very interesting what you said about succeed at least rise even in the basal condition and so on when we talk about the antioxidant we talk about selenium but as we said the beginning it's part of the antioxidant strategy to illustrate a bit more on sodium and vitamin E for instance and the winning conditions actually for five many years ago a lot of research was developed in order to study deficiency symptoms and it came up that often vitamin E and selenium they making make ISM mechanisms and I would say here in this illustration it is really to show that so the vitamin E is incorporated in in between the fatty acids in the cellular membranes and the loosest iron hacks today is the selenium dependent one is really supporting this ants accident system by vitamin E so the two of them together create a very strong protection of the cellular membranes and again and it is easy to manipulate will the cellular membranes and the fatty acid composition so every time you start to introduce and saturated fatty acids into the feet for the pics of chickens you also start to manipulate and will the fatty acids and more unsaturated fatty acids may actually also create increased or enhanced risk of oxidative stress okay and the piglet and the particle phase in phase four in zones yeah I'm eating a lot of omega-3 and Sons they're just normal it could be that they are eating some Omega free because we also know that omega-3 fatty acids are very bioactive and have a lot of biological effects on the immune system in general but I think what is important is to consider when do we actually start will our antioxidant manipulation and in my eyes it's it's probably too late if we start on the day of weaning maybe we need a strategy where we start much earlier on why the piglet for instance is suckling the sound because if we want the selenium to be incorporated into the ciliary proteins and the the piglet and to be there where the infection is starting namely after weaning we need to introduce it earlier on so it should be ready for primetime and and I think very often when we consider these dietary strategies by which we can actually enhance robustness of piglets and maybe disease resilience we we need to consider when to be stopped as early as possible and maybe starting with ourselves with a breeder first yeah and yeah to continue that we know that regarding selenium research a lot of very nice results were done by Don Mahan and we know that when we increase selenium in the diet we can also easily increase this venom in the colostrum and milk of the south and in that way we can actually transfer the suckling pig --let's and however we also know that not only selenium but actually also micronutrient deficiency we know that from human beings that children suffering from micronutrient deficiency they are also more prone to infectious diseases and I think that we have to consider that as well for the piglet post weaning that do we actually are we actually focusing enough on making support of the immune system when we need an activator peri-peri began before information on mammals I would say on pigs on humans and rodents and so on but I know that burnt is always challenged by by the knowledge on avian immune system of young reaction so what is a challenge for the avian mineralogists that you represented a belt discussing all these aspects and realized how little we know actually about for example redox potentials in immune cells or uptake of selenium transport mechanisms and the like from our perspective what we can do I think is to provide the tools the methods the reagents for nutritionists for researchers on redox potentials to do such studies and in the immune cells and so with a avian genome available now for extended period of time we have made progress we have identified a lot of these inflammatory cytokines which we mentioned before but we I think have to go on we have to identify some of these genes which we do not know whether they are there in the chicken yet but which yeah which play an important role in in mouse models or maybe even in the pic where we have much more knowledge than we have in the avian system we also have to to identify the cells which produce these components and understand how they work what I find personally very challenging and interesting is to see how a microbial products in the gut and how nutrient factors and absorbed from the gut impact on those cells and also help to regulate those cells and regulate upregulated or downregulated inflammatory responses in the East issues and for that we also need to understand how these mechanisms work and what other receptors and what are the responses of these cells so identification of factors the cells and their response that is really what we want to do and we are making a bit of progress okay that's good sounds good it sounds like in a couple of years we should be better able to deal with inflammation immune system okay thank you very much review so I think now we can open the question session and I'm sure that we have received quite a lot of questions from the web participants maybe the first question what is the importance of oxidative stress in the regulation of the immune response you already addressed a little bit that but I think now it's quite good time to really share on your feeling on that so maybe Peter oxidative stress is related to actually oxidation of lipids proteins DNA and for many here's the lipid peroxidation was something which was a topic of research and there is hundreds and hundreds papers described in mechanism and so on and so forth but protein oxidation came recently on the stage and protein oxidation and many cases could actually affect immune cell viability in a Cell action however if we look at the traditional antioxidants like vitamin E vitamin E cannot protect against protein oxidation but today topic is selenium selenium is a part of humourous antioxidant enzyme including methionine sulfur oxide reductase B which is specifically involved in prevention or protein oxidation that's a topic of the future research to look how cilium can affect those enzymes and houses and vimes can prevent protein oxidation and what consequences are but that will help us to explain how oxidative stress detrimental effect of immune system so in the case of stimulating or having more oxidative stress will affect the immune response well yes Yonkers will affect the performance of the cells and it pretty much depends on on the magnitude think of the state of stress situation membranes are fluid yeah and this fluidity is very important for example for the communication between cells based on that it will also impact on the communication effect on oxidative stress on the immune system ah si yes thank you I think that has been shown nicely so it has been shown in knockout mouse models that if you if you delete some of these Salerno proteins specifically in T lymphocytes for example then it's not only that the T lymphocytes not function anymore but they cannot have the B cells to produce antibodies okay so so there this communication is also inhibited and it seems as if there is a very important role to the importance of integration and we have to make integrative mere knowledge integrative biology and so on maybe we asked for the second question about what is the immune response under oxidative stress situation well at least in the chicken I think there's comparatively little knowledge what it is precisely and one of the issues is to have good models to look into it yeah I don't know what kind of models have been developed and in swine or other domestic animal species speaking if we look at the system response and heat stress for example mycotoxin contamination of the feed again even system will be compromised at least in those common stresses which are known for poultry and pig industry it's very clearly showing that the no system can be compromised under stress and the source resistance because today we are talking about oxidative stress as a molecular mechanism or major stresses in poultry and pig production which means it could be environmental stresses it could be nutritional stresses it could be biological stressors but it's a molecular level we will be talking about oxidative stress which is imposed in the insect issues and this balance in redox potential and those consequences related to immune system which we already discussed today mm-hmm you want to compliment a shallot yeah just like to emphasize that we need some know we need to know more about what is actually the nutritional requirement once the immune system is activated because it might be very high demand for some specific nutrients including here selenium vitamin E and so on once we have activated all these immune cells while when it's not activated it might be much less so I think we need to set up some good models in order to combine these various mechanisms and also look for of course clinical signs of an infection and so on to link the data together and in that way you learn much more about integration of oxidative stress and family reactions and then what is rain what is the demand for new tree so difficulty when you talk about that is adjusting the dietary supply and stress condition it's we see it's already happening and so on so you need to prepare the animal or two to be in the situation that you provide before potentially the stress is arriving so how do you think about that what we should do on the different nutrients and so on what should be you know incorporate more prepares the animal to have some reserves and so on in my lab we use a lot of infection models will poultry and swine and I think we do need to somehow challenge the animals it could be of course heat stress but infection challenge may not create the same direction so mechanisms as a heat stress model and I we need to learn much more about the communication between immune cells and signals here and and be more what we can say consider much more what kind of disease what kind of stress are we now researching yeah yeah and how we can utilize this module in fact to prepare the solution the teleport okay this question a practical question do we know if increasing the dietary supplementation of antioxidants I suppose selenium vitamin E and so on announce the contents of this antioxidant into the immune cells may be burnt or yeah I must admit I don't know so we have some question so we don't directly the incorporation of until she's not in the Indians yeah yeah you you may be able to rest that question more precisely yeah it's it's possible to and also increase for instance the level of vitamin E in immune cells by dietary supplementation now the problem is sometimes if you need to analyze that the actual content of a micronewton immune cell you need also to harvest enough immune cells in order to actually being able to measure it and this can sometimes be extremely difficult for instance in the gut just harvesting immune cells and be able to say well now we have this macrophage from the god how much vitamin E or selenium selenium proteins does it contain because we often the gut immune system is a largest immune system of the body but it's difficult to analyze by itself you know but there are good reasons for it yeah I would say because as I mentioned before it's very complex and it is interesting because I talk to you to Mouse immunologists who work a lot on the gut tissue and they extract cells from the gut issue all the time and look at these cells what they do now ask them what do you think how which percentage of cells which are sitting in the guts do you actually extract for your cell culture work and so on they said well we calculate roughly 1/3 mm-hmm so we always should keep in mind that these studies only give us a some idea but it might not reflect precisely the number inside the environment which is also an issue we may lose a lot of cells and lose a lot of information which we actually would need yeah that is a problem with in particular with the gut it's much easier if you use lymph nodes or yeah other tissues so still some somewhere to do even though they are also very complex yeah I mean maybe another question as the actual selenium on Crimmins adapted to support the actual swine and poultry commercial I breed in case of challenges first of all we need to mention that all requirements which we know for requirement for example selenium for pigs and poultry that we devised or developed in more or less physiological conditions but in commercial conditions importer at forty farms or pig farms we don't have ideal conditions so there will be all these challenges and in this case the requirement might be high we have some kind of restrictions on selenium because in the u.s. maximum supplementation is poor in 3 ppm the same more or less in Europe and recently organic selenium was put a restriction on point to supplementation we cannot give to them more than point to legally but in many cases my feeling is and my research is actually on an to access system showing that yes in challenge conditions the requirement might be higher but we need to resolve this question how we legally can supplement more one point is to use form of saline which are more available to deliver more selenium with the same dose of selenium this was the whole concept of organic selenium coming here which means by using organic selenium we can deliver most lenient with the same dosage if the point 2 ppm can give a good response we should have to say maybe we need to need to simply mount a bit more and there's another thing I would like to say is also that often the nutritional or at least official nutritional guidelines they are based on studies which were actually performed on in the older days where we did not have these highly prolific cells or high performing animals so again I think we should keep in mind that again having this more intensive production might actually put a pressure on our animals so not only during challenges but also on a general basis the demand for some nutrients might be different from what we had in the older days ok interesting next question our selenium can be involved in the transfer immunity from breeders to progeny what is a main selling no cotton involved so not only the selenium transfer versus selenium acelino proteins transfer first of all during embryonic development there is a transfer of first selenium from the egg yolk and egg white into the developing embryo we know that first two weeks of development Selenia will come from the egg white in last week or the embryonic development selenium is coming exclusively from egg yolk now the question is what about Savina protein expression at the same time this work is still at the beginning because we did a lot of work with selenium itself but the next step to look the expression of individual celina proteins during embryonic development and then to see how this can affect immune system development because we know that G when chicken is hard [ __ ] the immune system is not developed completely and therefore this period of transfer would be the major period to have a look and to make sure that we delivered enough selenium to the newly hatched chick to be involved in the synthesis of those cell or in expression and since absolves sending the proteins which eventually will help to mature immune system more efficiently we looked at the response of the immune system when you simply mount the breeder points like if I remember in the past you had some tries on the vaccination response expose the result I would not put them in the mainstream says and this is already done yes there are some indications it is a optimal selenium supplementation can help but we need more work in this area to see how we can affect actually and look in on all these new the new developments like a maternal effect on the progeny we know that you know the 3d no breeders can affect she can call it after harsh but this is a just as a very beginning we need to have a look more specifically on selling a protein expression how they experienced during at least first week post hajj with because we know that during first week post hajj the antioxidant system is compromised because the level of vitamin e for example accumulated up to the maximum during embryonic development at hatch in time so there's a maximum for the first two weeks post harsh concentration of vitamin a decrease most twenty times therefore the encode system will be compromised however there is a compensatory effect as an ox and like glutathione peroxidase activity goes up so it's all about balance the ball balance of decreasing vitamin E and increasing expression of antioxidant enzyme let's say area very exciting one and I hope in the nearest future commentar well I think interesting we even in mouse models there's very limited information on the effect of selenium proteins hematopoiesis so the production of of cells from the bone marrow or from the thymus there are some effects but it's all at this point not really consistent and not giving a consistent picture so even in these very well-established animal models we have comparatively limited knowledge about that I would challenge you as just a question thinking about things we talked about growing anymore performing animals and so on but what about the aged animals I would say yeah and part of it ladies find some today we are going beyond hundred weeks and so on what's that challenge immune system and the oxidative stress immune system balance there's a particular period which is really interesting that you start of lay yeah so that is really a challenge to the hand and the Gator dunno yeah it is well I mean the general consensus is that there is a immune or moist situation so there's some immunosuppression around that period when the hormonal system is changing layers start to lay eggs but it's not very well investigated so we have some indications we know there is some immuno suppression but how it works and whether any of these components play a significant role in that process that is not known at this point and even more importantly in old layers there are little knowledge and that is I think due to the immunologists actually who have looked into birds usually embryo was interesting the young yeah bird the first three weeks or so after hatch and what we quite often do is we look into juvenile birds such as four to eight to twelve weeks yeah very rarely into very old layers that's a new challenge for the last question wait a minute question is riving knowing that the organic source of senem leads to I kiss you selling the petitions of foremost Selena miss I mean how these de pots can be used by the animal in case of challenge in which tissue would be the best source to deliver the story dudu is specifically store with a selenium and do we specifically mobilize this tissue this question is very much related to the whole concept of organic selenium which I've been involved for last 20 years in developing this concept the whole concept is that there are two major forms of selenium it's a organic cell you mainly sell in a methionine which is coming from any feed ingredient so if you look at the selenium composition in wheat Valley it's mainly Salina methionine however the supplementation which started in 1970s it's sodium selenite and these two forms are completely different sodium selenite actually not the optimal form of selenium in the diet the only advantage of this form is just because it's cheap but cheap does not mean effective therefore the whole idea is that organic selenium means a form of silina methionine can be non specifically incorporated in proteins instead of methionine so the ratio could be let's say for one molecule of silina methane and we have a few thousand molecules of methane in however this incorporation potentially can build selenium reserves especially in muscles so during stress conditions we have protein catabolism including protein catabolism in muscles and during this protein catabolism zzz cell in methane can be released and can be used for synthesis of newly synthesized setting up proteins and there is a actually only one publication as far as I know showing that protostomes which are involved in protein catabolism actually activated in protein in selenium deficiency which means it could be adaptive response which means the selenium deficiency stress catabolism protein increase release of celini methane in additional synthesis of silina protein in establishing balance again I'm talking about balance so this is establishing balance so they're using all those selenium resources in the body the Samson which can help to explain how organic selenium is working however we need more neurons at one mm at least from the molecular mechanism how specifically it's happening okay one more question what would be reliable and practical biomarker to understand that which extent selenium is affecting the immune response in challenge animals I repeat what would be reliable and practical biomarker and we talked about biomarker before to understand as which extent selenium is affecting the human response under challenging conditions very good question very complex I mean the the real issue here is that we as we discussed before have different cells of the immune system in forming different functions so for each and every of these cell types we have to look at their precise function and how they function on a challenge condition so if we think about an early infection we would look at innate immunity cells and then we would want to see whether I would say in collaboration with those who have the knowledge to look into red ox systems to understand our V Salerno proteins regulated that would be I think a good marker because it can be done quite easily and the functional outcome of this would be actually at the end of the day the interesting Clarkson don't you want to see I just want to say that I think it depends on what is your challenge and what is your hypothesis because again if you are going to measure biomarkers and see selenium is really working you you need to again and kind of be very focused on what what do you ask for here so if it's oxidative stress and oxidative stress challenge you may focus on markers of that and link that to the immune cell mechanisms yeah good point so I already asked you the question or you're on and sound about see we talked about oxidative stress we talked about immune system and we talked about the effect or not I'm taking a means easy is the effect but I would say why in fact the immune cells specifically producing reactive oxygen species so it's not a question of nan lian highly producing animal it's also a normal way to kill or to help these animal to develop the immune response so as mentioned before I mean that is one of the I would say tricks or mechanisms of phagocytes to kill microorganisms we all know that h2o2 is pretty good in this infecting needling bacteria we use it at home and in other places also ozone is pretty effective in disinfecting water so these are very potent components and the immune system has evolved in such a way that these components are generated in in large amounts which led to the term because they need oxygen to do so it led to the term oxidative burst and so that produce huge amounts much more than is produced and on all the other conditions so we have to have strong counter regulatory mechanisms in order to avoid collateral tissue - yeah and I just I think a very important aspect of the whole system there are mechanisms yeah we are always talking about this balance but at the end we want balance and homeostasis and an animal dealing with everything and not consuming too much not challenging to achievement system and so yeah this actually free radicals it's a chemical weapon it's all they use chemical weapon to kill pathogens but chemical weapon is not specific the Amika weapon can kill phagocyte itself therefore the antitoxin system which actually developed to maintain under control first of all this production of radicals is very well controlled it's like a difference between nuclear power station and a nuclear bomb so this is a nuclear power station which means is control very well the production is needed however the protection is a key therefore the expression of those sarena proteins which I mentioned already which can actually be involved in redox balance maintenance in maintenance of protein oxygen prevented protein oxidation this will be the key to maintain the dangerous weapon under the control so free radicals can be positive and negative so at least an engineer today we didn't discuss that much only to see little barrier function yeah but of course I think that that we really need to control this oxidative stress do not control this we will loose the barrier function and then we really have a severe damage and that God will not anymore be able to absorb any nutrients and that can really a major problem and will accelerate the whole thing if you get a leaky gut yeah the Curia will get on the wrong side into the body and counter the immune system activate the immune system leading to inflammation leading to more oxygen radicals so it's a kind of a enhancing system here and that I think also important to consider thank you so I would like to stop the discussion now so for the question which have not been answered you will get a response on the feed channels I would like to warmly thank out three speakers Charlotte Benton Peter for the excellent discussion and so on I'm sure you will have more question I have more questions I wrote already some question and so on I think it was very interesting you will be able to listen again the program on fictional platform you will see your questions and you can also interfere with a fictional outfit channel dot online you can ask questions make comments and we will distribute to the speaker and feel free to really put your comments on on this webinar I should add that you can even get more presentation we run in Dubrovnik prior to the IPC in September 2018 session on strengthening the intestine frontier and Peter and burnt presenting in more details in fact the immune systems the oxidative balance and so on so I think it is interesting and by the way we give you a new appointment for the next live webinar in on AIDS of January on liquid additives the objective is liquid additive in the feedmill an opportunity of value so and before closing this live webinar last one of the year 2019 I would wish you a Merry Christmas and Happy New Year and I will tell you that 2020 will be a very more dynamic year for fictional because we will change the platform will have more communication we will organize more webinars will also launch short educational videos to illustrate in a couple of minutes the key mechanism Franzen's as we talked about immunity today and we will organize a water week during the world poetry conference starting with an opening conference on water from a nutrient to sustainability so thanks to the participants for the questions to our speakers today and really have a nice time for the end of the year and see you on a sub general thank you [Music]