The advances in the immunosuppressive drugs improved obviously the short term outcomes of kidney transplantation. However, the variable side effects and the long term organ toxicities, including the renal graft, represent great concerns.
Very good and interesting question! I think the key to the success and outcome of kidney transplantation and in general and other organs are just the development of new immunosuppressants and their selective inhibitory activity on T helper ancillary cells that extend IL-2 as a precursor to the immune reaction rejection!
I think I'm a moderate optimist to find some retard immunosuppressive forms that have a longer period of action, that they do not have any of the current or less undesirable reaction effects!
You are free to recommend your projects on this topic and to give you something now, and you can find the rest on my web site among my questions and project designers handle this topic or my correspondence with colleagues who have expressed interest in this very interesting area!
Regards Jasenko
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?
The development of transplantation medicine as a dynamic scientific disciplines, especially progresses past 30 years or so, thanks to finding more and more sophisticated immunosuppressive agents!
Do you also be expected to progress immunosuppressive therapy brought rapid development and application of xenotransplantation in human medicine!
Is xenotransplantation real future of organ transplants?Is xenotransplantation real future of organ transplants?
Due to lack of authority to limit the development of transplantation, a large number of scientists carried experiments within the species, which will hopefully help to the invention and the identification of the best animal donor organs to man!
Immunosuppression, immunoinhibition, immunodeficiency, is the suppression and weakening of the normal immune response of the organism as a consequence of the action of different substances found in the external environment or created in the body. Each transplanted body represents a foreign body that the body is trying to discard. In order to avoid this, it is necessary to take anti-rejection drugs (immunosuppressive medicines). There are numerous medications as well as their combinations, however, all have a common one - they must be taken as long as the function of the transplanted organ takes place. Because immunosuppression of the immune system's function is weakened, there is an increased susceptibility of the organism to infectious diseases and cancer, so not so often immunosuppression can cause undesirable side effects.
Anti-suppression drugs (immunosuppressive drugs) have been the success of organ transplantation, which we are witnessing today. Unfortunately, they do not only act to prevent rejection of transplanted organs, but have many unwanted effects on the body. Especially important is reduced resistance to infections caused by immunosuppressive drugs. Treatment protocols are not unique to all transplantation centers. Transplant Centers decide on certain immunosuppression protocols according to the results of published clinical trials and their own experiences.
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation [accessed May 11, 2017].
Immunosuppression, immunoinhibition, immunodeficiency, is the suppression and weakening of the normal immune response of the organism as a consequence of the action of different substances found in the external environment or created in the body. Each transplanted organ represents a foreign body that the body is trying to discard. In order to avoid this, it is necessary to take anti-rejection drugs (immunosuppressive medicines). There are numerous medications as well as their combinations, however, all have a common one - they must be taken as long as the function of the transplanted organ takes place. Because immunosuppression of the immune system's function is weakened, there is an increased susceptibility of the organism to infectious diseases and cancer, so not so often immunosuppression can cause undesirable side effect!
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation [accessed May 11, 2017].
Well done to all types of immunosuppressive improved but I think that the closest that calcineurin inhibitors something like cyclosporine or tacrolimus, because no specific organic transplants where they gave remarkable results in the inhibition of rejection, acting on the inhibition of T helper cells and other structures (inhibition IL-2), etc.! !
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/2 [accessed May 11, 2017].
Chapter XII FINANCIAL ASPECTS immunosuppressive
THERAPY
Financial Aspects of immunosuppressive therapy
O. Riđić, F.Gavrankapetanović, Riđić G., T. Jukic, O.Slipičević, J. Karamehic
12.1. Introduction
12.2. immunosuppressive protocols
12.3. Examples of funding immunosuppressive therapy
1. The costs of immunosuppressive drugs
The used second (immunosuppressive) drugs in the period 2006-2008.
12.3.3. Only the number of patients treated with immunosuppressive lijkekovima and total and
average consumption of drugs used (per patient) in FBiH
in the period 2006-2008
12.3.4. Only the number of patients treated with immunosuppressive agents including
generic name, number of treated patients, the number of units and the total amount to BAM, in
FBiH for the period 2009-2010.
4. Discussion
5. Conclusion
6. References
XII FINANCIAL ASPECTS immunosuppressive therapy
12.1. Introduction
Any time, when we have to transplant an organ or organs from one person to another, the recipient's body tends to reject foreign (implanted) body (eg. Body). In order to prevent the rejection of modern medicine uses potent immunosuppressive agents. Today, immunosuppressive therapy is designed to suppress all immune responses, including those on: bacteria, fungi, viruses, malignant tumors, etc.. The cost of immunosuppressive therapy are an essential part of the cost of whole organ transplantation. In this paper, the authors analyzed the cost of immunosuppressive therapy in the two countries: the United States and entities of the Federation of Bosnia and Herzegovina (ie. The FBiH).
Medical and pharmacological interventions that require changes in the patient's regime, among those patients whose treatment regimes "do not follow the prescribed procedures and rules vary from patient to patient, and from 50 US states. Prominent target companies for patients undergoing organ transplants, slowly but certainly, runs more towards almost complete (ie. universal) approach immunosuppressive drugs, given that this category of costs usually outpace the annual cost of hospital (ie. the hospital) and outpatient eg. ambulatory and home care).
Immunosuppressive regimens are expensive in the socio-economic environment of limited resources and constraints. Recipient body reacts and responds to new transplants trying to discard them. The most common type of rejection is called "acute rejection", which potentially can occur at any time, in inadequate immunosuppressive environment, but usually occurs within a few days after transplantation. In order to diagnose rejection must use expensive procedures (eg. Biopsy, radiological tests, etc.). Cancellation of acute transplant rejection requires more immuno-suppression, increased use of additional therapies, more frequent monitoring, clinical examinations and more intermittent hospitalization, in other words all translate into higher costs of use (1-6). Preliminary research literature shows that the number of patients in FBiH who required immunosuppressive drugs from 2009 to 2010 increased by 35, which is 27.3% more.
In accordance with the rules laid down and issued by the Federal Ministry of Health on treatment with immunosuppressive drugs for all patients who have undergone organ transplants, Commission for immunosuppressive treatment, as part of the Federal Bureau of insurance and reinsurance companies in Bosnia and Herzegovina, giving authorization for the use of immunosuppressive drugs , as a permanent therapy after organ transplantation. In 2009, the immunosuppressant drugs have been used by 128 patients. Immunosuppressive drugs should be used by all patients, during and after organ transplantation.
Treatment options must also be assessed taking into account the socio-economic barriers, which can carry serious consequences of non-acceptance and non-compliance to this treatment to improve life. Examples of these barriers to quality and long-term immunosuppressive treatment, for example: unemployment, chronic low income, insurance status and quality of coverage, insurance (broker or impose terms of the third party), etc. Researchers Himmelstein, Woolhandler and others at Harvard University in Boston, Massachusetts, USA, have found that the majority of all bankruptcies in the United States was a problem caused by medical expenses. In 2009, President Barack Obama is trying to alleviate this problem by signing a law entitled "Protection of the patient and the law on availability." This legislation aims to extend the previously insufficient 36-month period federally sponsored medical care coverage, Medicare. (7-12)
Apr 6
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/3 [accessed May 11, 2017].
The continuation of my answer to your question:
Assessment of future transplant recipients is another key element in the best socio-economic use of immunosuppressive therapy. When implemented and applied correctly, this assessment can bring long-term benefits of achieving further immunosuppressive therapy. In addition, psychological, cultural and multi-cultural issues need to be evaluated carefully and in a very delicate, balanced and fair way.
In the course of finding the ideal treatment regimen for reducing morbidity and mortality, while maximizing quality of life and optimizing costs a major challenge for the transplant community. Pharmaco-economic analysis can provide useful methods and tools for achieving serious goals. The objectives of this study are to give the readers with a basic understanding of pharmaco-economic principles and review of published pharmaco-economic analysis, relating to immunosuppression as an essential part of organ transplantation. Pharmaco-economic studies are broadly defined as "a description and analysis of the cost of treatment therapies for health systems and society". This is a process in which the costs of certain therapies assessed in relation to outcomes. (13-16)
Regards
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/3 [accessed May 11, 2017].
I give a basic overview of the previous imo-suppressants, from their book, issued in 2012g. Under the title "Immunosuppressive Therapy and Its Use in Organ Transplantation", their activity and significance, which could further overcome the immunoblotic barrier through xenotransplantation by further training under these same principles. This book is entirely in electronic form on my CV on the web page of RG !
Introduction
Even 40 years ago, the first successful kidney transplant was performed between identical twins. The first attempts were unsuccessful or with a small amount of success because there was no adequate immunosuppressive therapy. The recipient organization sought to reject a foreign body by defensive immune response. Because of this, the experts worked on designing medications to develop effective immunosuppressive therapy. The first results are noticed in the practice of the 60s when the first immunosuppressive agents are being applied. Among the first are azathioprine (Imunran) and steroids. After some time, other medications such as mycophenolate mofetil that are slowly suppressing are occurring. From the age of 80, apart from ciclosporin, monoclonal antibodies block the function of T lymphocytes, resulting in immunosuppression. Monoclonal antibodies, which are routinely used with the CD3 glucoprotein, have a molecular weight of 20 kDa. OKT3 or mouse immunoglobulin, which is commercially used, has the ability to block the function of all T lymphocytes possessing this receptor. In the last 15 years many immunosuppressants have appeared that have a wide clinical application. Dr. Joseph Murray received the Nobel Prize in 1990 for successful work on kidney transplantation. The main strategy of clinical application of immunosuppressive is the reduction of the aloimic response to the transplanted organ. There are 4 major strategies in clinical practice: induction, prophylaxis of acute rejection, maintenance of immunosuppression and acute rejection therapy. Of course, the main goal of transplantation is to achieve absolute tolerance to the transplant, which will take time. For now, preventing transplant rejection is achieved by using powerful immunosuppressive medications at strictly prescribed doses to avoid toxic effects. Acute rejection occurs if no adequate suicide response is achieved. In cases of overactive immunosuppression, complications such as viral infections (Cytomegalo virus) or malignancy such as cancer of the skin, B cell lymphoma, Kaposi's sarcoma etc. may occur. For example, clinicians in the area of transplantation have limited possibilities to achieve effective results.
Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/3 [accessed May 11, 2017].
Xenotransplantation
Jasenko Karamehić,
INTRODUCTION
Xenotransplantation is the transplantation of living cells, tissues or organs, from one species to another. Such cells, tissues or organs are called xenografts or xenoternal embryos. Humane xenotransplantation offers potential treatment for the terminal stage of organ failure, which today represents a major global problem. The dimensions of this problem as well as the advances in immunotherapy triggered a great interest in the potential use of animals instead of humans as organ donors. Researchers in this field focused their efforts on suppressing the immune barrier that prevents long-term survival of the xenograft. Xenotransplantation is also linked to many medical, legal and ethical issues. The use of xenotransplantation for clinical purposes would imply a multidisciplinary approach to provide a more complete response to various questions related to the use of xenografts for human purposes. In this regard, safety, ethics and regulatory aspects of xenotransplantation are now working to achieve the best conditions in which the ratio Between risk and benefit was as favorable as possible.
DEFINITION
Xenotransplantation implies any procedure involving transplantation, inplantation, infusion into a human recipient of either living cells or from inhuman animal sources, whether human body fluids, cells, tissues, organs that have exacerbated contravention of living inhuman cells to the tissues or organs.
(USA Food and Drug Administration / FDA, 1999; FDA, 2001) This is a reference to here the reference number
Xenotransplantation products must be alive. For example, human skin cells that grow outside the body, on the base of inhumane cells, and are used to reconstruct skin in humans, can also be considered a xenotransplantation product. This category of procedure is included in the definition of xenotransplant because, Scientists consider potentially transmitting infection with such procedures to have similarities with the transmission of infection in the transplantation of living animal cells, tissues or rabbits to a human donor.
Apr 21
Is xenotransplantation real future of organ transplants?. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants2 [accessed May 11, 2017].
Transplantation of the 20th century
In beginning of 20th century there are also some American doctors John Davis and John Hopkins who published their results mostly in xenotransplantation. In their experimental transplantation they wanted to learn more about experiments and which mechanisms are supporting or obstructing it.
Joseph Lister pioneered the field of aseptic surgery based on Louis Pasteur's advancement of bacteriology. It was helpful for prevention of sepsis and brought to decreasing level of infection of transplanted organs in operating rooms.(22) Big problems for surgeons during the transplantations were complications as thrombosis, aneurism bleeding etc. This was improved after Second World War introducing fine surgical monofilament fiber which prevents these complications and insured safer anastomozing of the blood vessels of transplanted organs. Discovery of heparin as very potent anticoagulant in 1960 reduced complications such as thrombosis and embolism.(23)
Introducing of direct artheriography as very important diagnostic method for blood vessels insured preventions of complications in posttransplantation period. Also usage of special grafts for angioplasty increased results of transplantation.
Figure 1.Alexis Carrel (1873-1944) Nobel Price for medicine in 1912
Figure 2.Theodor Kocher (1841-1917) Nobel Price for medicine in 1909
Famous names of that time in surgery were Morel, Murphy and Carrel (figure 1.) who is known as the founding father of experimental organ transplantation because of his pioneering work with vascular techniques (24) Theodor Kocher (figure 2.) was famous in extirpation and transplantation of thyroid gland. The American Charles Guthrie and Carrel transplanted dogs head on others dog shoulders in 1954. In that time Nobel price in field of transplantation was won by Leonardo Hill.(25) That price was subject of many discussions because that should be won by Carrel and Guthrie who, according to Medical Public of these days had better results of improvement of blood anasthomosis in transplantation. The techniques used to join the vessels together were those developed and described by Alexis Carrel, who had been a young surgeon in Jaboulay's unit, and in fact, the techniques of vascular anastomosis described by Carrel are exactly those still used in renal transplantation today. Carrel subsequently moved to the Rockefeller Institute in New York, but he continued his organ-transplantation work until the beginning of the First World War. Indeed, in a prescient lecture in 1914, he said that the technical problems of transplantation were essentially solved, but until some method was developed to prevent the reaction of the organism against the foreign tissue, there would be no clinical application of organ transplantation. Between the wars, experimental transplantations were occasionally performed, but there was no advance in knowledge. There was a serious clinical attempt by a Russian surgeon, Yu Yu Voronoy, who transplanted cadaveric kidneys into six human recipients, but without success.(27,28)
The modern era of clinical transplantation began in Paris and Boston after the Second World War, and one highlight of postwar efforts was the small series of transplantations of cadaveric kidneys performed by David Hume at Peter Bent Brigham Hospital in Boston. No immunosuppression was used, but some kidneys did function for days or weeks, and one for several months — no doubt because of the immunosuppression resulting from the profound uremia in the recipients.(29) Enormously encouraged by the successful transplantation between identical twins that had shown that renal failure could be reversed completely, those pursuing immunosuppression, in Boston and Europe, now directed all their efforts at total-body irradiation.
Although such irradiation did achieve immunosuppression, however, it also produced profound marrow aplasia, which led to patients' deaths from overwhelming infections. By the early 1960s, it was clear that total-body irradiation was not the solution.(30)
During the early stages of the Second World War Peter Medawar was asked by the Medical Research Council to investigate why it is that skin taken from one human being will not form a permanent graft on the skin of another person, and this work enabled him to establish theorems of transplantation immunity which formed the basis of his further work on this subject.(31) When he moved to Birmingham in 1947 he continued to work on it, in collaboration with R. Billingham, and together they studied there problems of pigmentation and skin grafting in cattle, and the use of skin grafting to distinguish between monozygotic and dizygotic twins in cattle.(32,33)
Figure 3. Double organs transplantation pancreas and kidney
Medawar (figure 4.) was Nobel Prize awarded in 1960 with Burnet for their work in tissue grafting which are the basis of organ transplants, and their discovery of acquired immunological tolerance. This work was used in dealing with skin grafts required after burns. Medawar's work resulted in a shift of emphasis in the science of immunology from one that attempts to deal with the fully developed immunity mechanism to one that attempts to alter the immunity mechanism itself, as in the attempt to suppress the body's rejection of organ transplants.(34,35,36)
Figure 4. Peter Medawar (1915-1987) The Nobel Prize in Physiology or Medicine 1960
Conclusion
Modern medicine has triumphed over many challenges and overcome many hurdles to achieve successful organ transplantation. The goal of organ transplantation is to provide the patient with an active and happy life, instead of the untimely death from fatal disease of a vital organ. Today the transplantation has become a massive field. The great advancement of medicine has enabled us, through the transplantation of organs, to minimize the death rate and minimize the enormous material expenditure in society.
Apr 30
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Jasenko Karamehic · 43.50 · Clinical Center University of Sarajevo
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Starzl E. T.: Expierence in Renal Tranplantation, Saunders Comp. Str. 363-370, 1964.
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Holman, E: Protein sensitization in isoskinggrafting. Is the latter of practical value? Surg. Gynecol Obstet 38: 100-106, 1924.
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Corresponding author:
Prof. Jasenko Karamehić MD, Clinical Center University of Sarajevo,
Is xenotransplantation real future of organ transplants?. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants [accessed May 11, 2017].
Of course, establishing a new species-animal origin as possible potential donors in xenotransplantation whose genetic system HLA and MHC much further and different from our human HLA complex will require a much wider, better and more advanced laboratory or immunological laboratory tests at each stage of the stages before the molecular characterization, the cross matching serum donor and recipient, DST (donor specific transfusion, elimination of cytotoxic antibodies and their constant measurement and removal, plasmapheresis and measurement srtalno cytokines and many more new things as bis is successfully started this process! Today's clinical immunology and its tests are an excellent basis for upgrade other sophisticated advanced and sensitive tests, because though it is not a allogeneic transplant within the same species but a lot more complex with other animal species and will be, and other potential problems such that most of these animals infected with something and, giving imunosuprewsije is a big problem reduce selective T cellular immunity and inhibition of T helper helper cells is has to work very selectively and carefully in order not similarly GVHD at the transplant bone marrow or here in parenchymal organs, which are not exempt from the potential risk of immunosuppression and the derogation of immunity, which tends to spread these microorganisms in
Is xenotransplantation real future of organ transplants?. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants/2 [accessed May 11, 2017].
14 KSENOTRANSPLANTACIJA knjiga pogl...Transplantacionoj imunologiji!.doc
This chapter you can found on my CV in electronic form on RG!
Belatacept, a fusion protein composed of the Fc fragment of human IgG1 linked to the extracellular domain of cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), selectively inhibits T-cell activation through costimulation blockade.
However, its administration is not a single dose and it does not convey a life long immunosuppresion. Belatacept is a step forward in IS while does not induce kidney damage as usually calciurin inhibitors do.
I understood that the question referrs to an single shot drug which would enable a life long IS. I am not aware of such a development, yet. A possible attempt would be to reach for tolerance development. This topic was exhaustively researched by Polly Matzinger.
Kind regards, Michaela