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!
We shouldn't forget that xenotranslantation carries a lot of problems, among which the diseases transmitted from animals to man. I don't think that xeno is the real future for transplantation
Thank you dr., Maurizio Salvadori, that it may be just one of the problems but I think that the science in its development in xenotransplantation have to deal with this and try to find the best solution!
How can we overcome the immunological barrier between different species?
Improving the existing immunosuppression and immunodiagnostics especially in typing data into before transplant stage, because this is a much more demanding immunological treatment and diagnosis and possible donors but also a potential recipient, because they belong to different biological species, and is therefore a discrepancy tissue much higher than in human allogeneic transplant !
What type of species do you think are the closest to be source of organ donation in human medicine in future?
So far, tests have shown that the closest as possible organ donors are primarily pig and monkey!
Do you will have to expand the existing range of clinical immunoessays in xenotransplantation is monitored and applied so far or can remain existing?
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 immunocompromised !!
Sir,
What is the Cost-benefit analysis (CBA), Cost-Effectiveness Analysis (CEA) and Cost-Utility Analysis (CUA) for the above approach ?
That if it came to life xenotransplantation of organs we will see the cost benefit, it will be seen and financial effect but I think that if patients successfully obtain transplants that would be cheaper for example kidney or pancreas of hemodialysis or from complications of diabetes ... .. but it will check only when the project invocations, now it is difficult in advance to talk about it, one can only assume ...!
And my last question professor, will further progress in area of xenotransplantion decrease requirements for alogenic transplantation?
Best to have more sources of organ donation and I think if you ever start to not be able to replace allogeneic transplant, which will always be needed and quantitatively and qualitatively, because they are less biologically-immunological barrier, because of the same species-as opposed to xenotransplantation, where sone much bigger!
Do not be the last question, given that you are a specialist clinical immunologist and that you are very young and at the start of their careers showing great interest in the field of transplantation immunology I'm at your disposal to cooperate in this for me is very attractive and unusual the important and complex field of medicine!
I suppose that it will be maybe future according worlwide shortage of organs is not enough and 25%-30% of patients who need organ die in waiting list .
I agree you respected professor Halima Resic, these are exactly in that order problems to be solved and much more else, but I'm optimistic in some distant future that this will be one of the most important resources for a transplant!
I think that you as head of the clinic for dialysis with a large number of patients best recognize how good would come another source for organ donation!
Dear dr.Dmitry,
As for the organ transplant she has found a place where there has been a terminal organ failure and death where the body is also the death of the patient, excluding kidney dialysis as a treatment!
As for the second of your questions fully agree with you that we should do everything in the field of prophylaxis to prevent end organ phase stage that is irreversible and transplantation where the only way of substitution of diseased organs to patients in general survived!
As for the transplantation of the brain I was with this problem have not worked a lot!
My opinion is that the smaller problems may have medical or are so great ethical, because it is still brain that gives us a complete personality, specificity and rightly open questions to be answered, I think that it should be dealt with multidisciplinary, medical doctors, sociologists, psychologists ... . and many other experts ...!
The patient must take all the time immunosuppressive drugs in order to keep the transplant, because he would be without it, our immune systems rejected!
Bosnian -Serb-Croatic languages is the same !
Što se tice transplantacije organa ona je nasla svoje mjesto tamo gdje je doslo do terminalne insuficijencije organa i gdje je smrt organa ujedno i smrt pacijenta , iskljucujuci bubreg jer ima tretman dijalizom!
Što se tice drugog Vaseg pitanja potpuno se slažem sa Vama da treba uciniti sve na podrucju profilakse da ne dodje do end organ stage faza koja je ireverzibilna i gdje transplantacija jedini nacin supstitucije bolesnog organa, da bi pacijent uopste prezivio!
Što se tiće transplantacije mozga ja se tom problematikom nisam puno bavio!
Misljenja sam da su manji problemi mozda medicinski ali su zato veliki etički , jer je ipak mozak taj koji nam daje potpuni subjektivitet , specificnost i spravom se otvaraju pitanja na koje treba odgovoriti mislim da to trebaju rjesavati multidisciplinarno, medicinari, sociolozi, psiholozi .... i mnogi drugi strucnjaci...!
Da pacijent mora uzimati svo vrijeme imunosupresivne lijekove kako bih odrzao presadjeni organ , JER BI GA BEZ TOGA NAS IMUNI SISTEM odbacio !
Dear Dr. Dmitry,
On one part of the question can you as a transplant immunologist answer! Yes, and when a patient is taking immunosuppressive therapy orgnizam rejects organvi mention kidney! Yes it is true and you are absolutely right!
Or immunosuppression works by inhibiting celularniimunitet, especially helper T helper cells to secrete IL-2 on a subpopulation cytokine cascade after the CD-3, CD-4, etc.! In other words immunosuppression very good work and this process can take years, that authority works well as graft! From my practice I have two cases that the kidney was functioning for over 25 years done here with us in Sarajevo, which is understandable rarity bowl rule because otherwise length Ages kidneys and other organs is much shorter!
On the other part of the question, unfortunately I'm not the best understood, and in it you can give your opinion, only that we explain a little better!
Greetings
Jasenko
Dear Dr. Dmitry ,
Na jedan dio pitanja mogu vam kao transplantacioni imunolog odgovoriti! Da i kad pacijent uzima imunosupresivnu terapiju orgnizam odbacuje organvi spominjete bubreg ! Da to je tacno i vi ste u potpuno u pravu!
Ali imunosupresija djeluje tako da inhibira celularniimunitet , posebno T helper pomocne stanice da luce IL-2 a on poslije kaskadu subpopulacije citokina CD-3,CD-4 itd! Drugim rijecima imunosupresija jako dobro djeluje i ovaj proces moze trajati godinama , da organ dobro funkcionise kao presad!Iz moje prakse imam dva slucaja da je bubreg bio funkcionalan preko 25 godina uradjen ovdje kod nas u Sarajevu, sto je razumljivo raritet inije pravilo jer inace duzina vijeka bubrega i ostalih organa je mnogo kraca!
Na drugi dio pitanja nazalost nisam najbolje razumio , te na njega ne mogu dati svoje misljenje, jedino da mi malo bolje pojasnite!
Pozdrav
Jasenko
Dear dr. Dmitry,
To be honest with me your comments very interesting, because the logical well documented and quite critical toward the official medicine, probably you have such an experience with the medicine or is it your assumption, I do not know but I do know that I like to have a dialogue with one towering intellectual like you, what great pleasure!
Please tell me a little explain this village very interesting comment about the brain and his transplant, I did not quite understand!
Regards from Sarajevo
Jasenko
"Dear Dr. Karamehic, What I meant is that there is a part of the brain that contains the blueprint of the organism. In the brain there is an algorithm to run the specific individual organism. So this part has to be transplanted as well, in order to allow the organ to be accepted by the receiving organism. I did not say transplant the whole brain, just a small part. It is a difficult question, if we only transplant one organ, for example kidney, then there have to be two parts, the original brain and the transplanted brain, and they have to be married together somehow before the kidney is transplanted."
Bosnian language:
Da budem iskren meni su Vasi komentari vrlo interesantni, jer su logicni dobro dokumentovani i dosta kriticki prema oficijelnoj medicini, vjerovatno imate takvo iskustvo sa medicinom ili je to Vasa pretpostavka, to ne znam ali znam da volim da imam dijalog sa jednim vrhunskim intelektualcem kao sto ste Vi, što mi pričinjava veliko zadovoljstvo!
Molim Vas da mi malo pojasnite ovaj Vas vrlo interesantan komentar o mozgu i njegovoj transplantaciji, nisam ga baš najbolje shvatio!
Regards from Sarajevo
Jasenko
Is xenotransplantation real future of organ transplants? - Page 3. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants [accessed Apr 6, 2017].
I can see, prof Karamehić, that your question has a great interest in academic circles. I would like to contribute with one more question. Since your question regarded future aspects of transplantation, could you please explain your opinion what percentage do you concider real for involvement of xenotransplantation in the future?
Distinguished Professor Resic gave a very relevant fact that 25-30 percent of people die on waiting lists and that they did not get never able to gain authority because there are not enough!
This is a very tragic fact and should do everything possible to seek alternative ways to increase the resources of organs for transplantation, for example, stem cells and their use in organ transplantation, develop better prophylaxis and diagnostics, so that at times prevent a possible terminal insufficiency authority on what is really well spoken distinguished dr.Dmitry and of course new discoveries in immunology, immunosuppression, in general medicine, so one day It could possibly start work and xenotransplantation!
Dr. Dmitry think I'd let this be of interest!
The analyzes in the various countries of the world agree
in that transplantation medicine
provides significant economic savings, but ....
A large number of so far performed transplantations of solid organs (about 1.5 mil.) Has brought significant medical experience, he developed the organization obtaining organ transplants and emerged as a rational and effective way to treat and to preserve the health and lives of a large number of patients. Transplantation medicine is widely accepted, and its results are greatly improved over time. Advances in immunosuppression have brought additional important qualitative developments.
Kidney transplant from a living donor has a longer survival by 20% compared to cadaveric kidney. But transplant from a living donor involves many more, and many unnecessary costs in the selection of donors. Quality of life significantly increases the transplanted people, and cost-effectiveness of transplantation has increased.
The important question is: who is today the rate of knowledge about the viability of transplanting human substance?
Except the area of the kidney, liver and in part, in the literature there are few relevant publications to account cost-effectiveness and cost savings in other solid organ transplantation.
Bosnian language!
Dr. Dmitry mISLIM DA BIH VAS OVO MOGLO ZANIMATI!
Analize u raznim državama svijeta slažu se
u tome da transplantacijska medicina
omogućuje značajne ekonomske uštede, no ….
Veliki broj do sada učinjenih transplantacija solidnih organa (oko 1.5 mil.) donio je značajna medicinska iskustva, razvio organizaciju dobivanja organa i transplantaciju afirmiralo kao racionalan i učinkoviti način liječenja i u očuvanju zdravlja i života velikog broja bolesnika. Transplantacijska medicina je općeprihvaćena, a njeni rezultati su vremenom uvelike poboljšani. Napredci u imunosupresiji donijeli su dodatne bitne kvalitativne pomake.
Presađeni bubreg od živog donora ima preživljavanje duže za oko 20% u odnosu na kadaverični bubreg. No, presadak od živog davatelja podrazumijeva mnoge dodatne, a i mnoge nepotrebne troškove pri selekciji darivatelja. Kvaliteta života bitno raste transplantiranim osobama, a isplativost presađivanja je povećana.
Važno je pitanje: koja je danas stopa znanja o isplativosti presađivanja ljudskih supstanca?
Izuzev područja bubrega, a dijelom i jetre, u literaturi postoji mali broj relevantnih radova koji bi objasnili isplativost i uštede kod presađivanja drugih solidnih organa.
Dear. Dr. Dmitry,
As for her transplant in various ways almost his whole life in particular transplantation immunology and immunosuppression!
Organ transplantation and its beginning and later development is the most meritorious clinical immunology and immunosuppression how to prepare patients for transplantation of organs, Tissue Typing HLA donor and recipient, all complex tests that are done to find hundreds more consistent HLA (MHC) gene locus and podsubpopulacije gene, then when the work dijagnostika- measurement of cytotoxic antibodies that can be limit factor in assessing possible further tests, natural relations individually to a patient, as with other sera continues to cross-coupling and search serum with cytotoxic antibodies least, or better similarities and coincidences tissue!
While doing so-called donor specific random transfusion in a recipient of the graft to be more consumed ii weakened naturally his immune system and give rise to plasmapheresis (removal from the blood of the recipient) special membrane circulating immune complexes are removed from the blood and thus improves mogučnog selective derogation immunity by inhibiting recipient T cells and helper subsidiary, through its inhibition of IL-2 relations its subpopulation of CD-3, CD-4, etc., as drivers immun system (trigger immune reactions)!
These are all physiological-immune reactions by type of natural automatism, in which causing a reaction of our antibody immunoglobulin-natural, with the mediation of complement!
Here our consciousness absolute, or do not affect the brain and the whole of which is autonomous, without the influence of noise, well-established and well-known principles of the immune response of antigen-antibody-complex with circulating immune mediation of human complement!
This is my explanation of the process after nearly 40 years of dealing with these prices and this job!
in the second part of your question, I will gladly give you their opinion but we it requires much more time because it is a nemediscinskim disciplines which I did not much acquainted!
Regards from Sarajevo
Jasenko
This is the original version in Bosnian language!
Što se tiće transplantacije njom se na razne nacine skoro svoj cijeli zivot posebno transplantacionom imunologijom i imunosupresijom!
Transplantacija organa i njen pocetak i poslije razvoj je najzaslužnija je klinička imunologija i imunosupresija kako u pripremi pacijenta za Transplantacija organa, tipizaciju tkiva HLA sistema davaoca i primaoca, svih slozenih testova koja se rade kako bi se nasli sto podudarniji HLA (MHC) lokusi gena i podsubpopulacije gena , zatim kada se rade dijagnostika- mjerenje citotoksicnih antitijela koji mogu biti limitijaruci faktor u procjeni eventualnog daljeg ispitivanja, naravno odnoisi se individualno na jednog pacijenta , jer se sa drugim serumima i dalje nastavlja unakrsno sparivanje i traženje seruma sa najmanje citotoksicnih antitijela , odnosno bolje slicnosti i podudarnosti tkiva!
Pa se rade tzv donatorske specificne nasumicne transfuzije kod primalaca grafta kako bi se što više konzumirao i i oslabio prirodnim putem njegov imunitet , pa se radi plazmafereza ( odstranjivanje iz krvi primaoca) specijalnim mebranama cirkulirajuci imuni kompleksi uklanjaju iz krvi i na taj način poboljšava mogučnog selektivnog derogiranja Imuniteta primaoca preko inhibicije T helper pomocnih stanica a, preko njih inhibicije sekrecije IL-2 odnossno njegovih subpopulacija CD-3,CD-4, itd , kao glavnih pokretaca imunogog sistema ( okidaca imune reakcije) ! To su sve fiziološke-imunološke reakcije po tipu prirodnog automatizma , na koje svijest odnosno mozak u konacnici nas CNS nemaju nikakvog uticaja i odvijaju se po principu (antigen-presad) izaziva reakciju nasih imunoglobulina-prirodnih antitijela, uz medijaciju komplementa!
Tu nasa svijest absolutno , odnosno mozak nemaju uticaja i sve se odvija autonomno , bez njenog uticaja po dobro uhodanim i poznatim principima imune reakcije antigen-antitijelo-cirkulirajuci imuni kompleks uz medijaciju humanog komplementa!
Ovo je moje objasnjenje ovog procesa nakon skoro 40 godina bavljenja ovim pricesima i ovim poslom!
na drugi dio vaseg pitanja , vrlo rado cu vam dati svoje misljenje ali mi ono zahtijeva mnogo vise vremena jer se radi o nemediscinskim disciplinama kojima nisam puno vičan !
Pozdrav iz Sarajeva
Jasenkio
You may find this artical paper-transplant be interesting!
See all ›
41 Reads
See all ›
6 Citations
Add supplementary resources
Download
Share
Transplantation of organs: one of the greatest achievements in history of medicine.
Article in Medical Archives 62(5-6):307-10 · February 2008
Source: PubMed
1st Jasenko Karamehic
37 · Clinical Center University of Sarajevo
2nd Izet Masic
37.88 · University of Sarajevo
+ 2
3rd Armin Skrbo
Last Djemo Subasic
Show more authors
Abstract
The history of transplantation is a scientific journey describing the medical community's effort to understand how the human body works. Humans have long realized the possibilities which transplantation of organs and tissue provides. Throughout history people have always been intrigued by the possibilities of the transplantation of organs and tissues. In the 6th Century BC Indian surgeons described how to reconstruct facial…
No recommendations yet
Jasenko Karamehic
Share this article
Article Transplantation of organs: one of the greatest achievements ...
On the other part of your thinking and your atahmente I have carefully read and recommended by each individual, can not say I have a great contemplative intellectual weight in relation to some other science of thinking, I have good, think twice, do you give your opinion ...! Honestly I am not acquainted with the philosophy nor with me is her deal but I will try! In any case, it is an honor to cooperate with you!
Regards
What is your expert opinion as to which segment of medical science can play the most influential part in the beginning of xenotransplantaion?
Good question!
Transplantation is a multidisciplinary field in which he participates almost more or less 15 to 20 medical disciplines and it is difficult to single out one or two areas and say that if their development run by xenotransplantation ...!
Yet the focus if I answer I'd put on two areas that have the most to this doprijeniti their development, this is the transplant immunology, imunospresija, in no way neglecting the development of transplantation surgery, diagnostics laboratory, virology, hematology, cardiology, endocrinology, gastroenterology, transfusion, infectious etc ... etc ...!
Dear Dr. Dmitry,
Thanks again for your reply!
I must say that your way of writing, opinion and a score has a very high intellectual and philosophical level ... ..!
This I say without false courtesy to have excellent Philosophical, sociological and psychological topics in the field of medical science! This is especially true of the brain and CNS complete!
To be honest I find this rare opportunity to speak to such an unique intellectual and philosopher! Why?
I do science, and with that is all fact, black is black, white is white, or better to say one plus one is two and can not be otherwise!
The job I'm doing more than forty years and I am used to thinking so earlier as a student, the day as a full university professor!
I confess that I did a lot of vican to it if it would be such and such, then it might be or not to be ... .what is the quality philosophy of which is based on kondcionalu and on possible assumptions ....!
This way of thinking is extremely high Philosophical and sociological level ... .. who have not had a chance earlier to meet!
Once again I am pleased and I feel very honored to have met such a high intellectual and a philosophy, with him and exchanged opinions and a lot learned from you because you are not from the ranks of the medics, with which mainly communicate!
I hope that we can customize the exchange of opinions in the future, which is my big wish!
I am sending you a couple of my references related to my position wiev opinion about organ transplants with different aspects of giving them individually one by one, because I think you deserve that ....!
regards
Jasenko
Postovani dr. Dmitry ,
Hvala jos jednom na Vasem odgovoru!
Moram reci da Vas nacin pisanja, misljenja I ocjena ima vrlo visok intelektualni I filozofski nivo…..!
Ovo kazem bez lazne kurtoazije da imate odlicne filozoske, socioloske I psiholoske komentare u oblasti medicinske nauke !To se posebno odnosi na mozak I kompletan CNS!
Da budem iskren meni je ovo rijetka prilika da razgovaram sa tako jednim unikatnim intelektualcem I filozofom! Zasto?
Ja se bavim prirodnom naukom I kod koje je sve fakt, crno je crno, bijelo je bijelo ili bolje reci jedan plus jedan je dva I ne moze drugacije!
Taj posao radim vise od cetrdeset godina I navikao sam da tako razmisljam ranije kao student a, dana kao redovni univerzitetski professor!
I priznam da nisam mnogo vican na ono ako bi to bilo takvo ili ovakvo , onda bi moglo biti ili ne mora biti….sto je odlika folozofije koja je zasnovana na kondcionalu I na mogucim pretpostavkama….!
To je nacin razmisljanja izuzetno visokog filozovskog I socioloskog nivoa….. koji nisam imao prilike ranije sresti!
Jos jednom drago mi je I velika mi je cast da sam sreo tako visokog intelektualce I folozofa , snjim razmijenio misljenja I puno naucio od vas jer niste iz reda medicinara, sa kojima ulavnom komuniciram!
Nadam se da cemo nataviti razmjenu misljenja I ubuduce, sto je moja velika zelja!
Saljem Vam par mojih reference vezano za moj stav opinion wiev o transplantaciji organa sa razlicitih aspekata dajem ih individualno jednu po jednu jer mislim da to zasluzuju….!
Lijep pozdrav
Jasenko
×
Financial Aspects and the Future of the Pharmaceutical Industry in the United States of America
Jasenko Karamehic, Ognjen Ridic, Goran Ridic, [...], Izet Masic
Article Financial Aspects and the Future of the Pharmaceutical Indus...
Financial Aspects of Immunosuppressive Therapy - Financijski Aspekti Imunosupresivne Terapije
Chapter
May 2012The Immunosuppressive Therapy and its Application in every day's clinical practivce
Oggi RidicOggi RidicFaris GavrankapetanovićFaris GavrankapetanovićGoran RidicGoran Ridic[...]Jasenko KaramehicJasenko Karamehic
ADVERSE REACTIONS OF CYCLOSPORINE IN PATIENTS AFTER KIDNEY TRANSPLANTATION
Article
Jasenko KaramehicJasenko KaramehicMensura AscericMensura AscericSanela RakicSanela Rakic
Transplantation of Kidney and Pancreas / Transplantacija bubrega i pankreasa
Book
May 2012Svjetlost
Jasenko KaramehicJasenko KaramehicContributing authorsContributing authors
ADVERSE REACTIONS OF CYCLOSPORINE IN PATIENTS AFTER KIDNEY TRANSPLANTATION
Article
Jasenko KaramehicJasenko KaramehicMensura AscericMensura AscericSanela RakicSanela Rakic
Add to project
Add resources
ECONOMICS ANALYSIS OF COSTS IN TRANSPLANTATION OF ORGANS IN FEDERATION ENTITY OF BOSNIA AND HERZEGOVINA/ EKONOMSKA ANALIZA TROŠKOVA TRANSPLANTACIJE OR...
Chapter
May 2012Transplantation of kidney and pancreas
Osman SlipicevicOsman SlipicevicFaris GavrankapetanovićFaris GavrankapetanovićOggi RidicOggi Ridic[...]Jasenko KaramehicJasenko Karamehic
Psychosocial aspects of malignant disease / PSIHOSOCIJALNI ASPEKTI MALIGNE BOLESTI
Chapter
May 2016TUMOR IMMUNOLOGY / TUMORSKA IMUNOLOGIJA
Timur CericTimur CericNarcisa PojskićNarcisa PojskićJasenko KaramehicJasenko KaramehicMarina Delić-ŠaracMarina Delić-Šarac
Imunosupresivna terapija i njena primjena u transplantaciji organa
Chapter
Jan 2012
· Imunosupresivna terapija i njena primjena u transplantaciji organa
Jasenko Karamehic
· Mithat Tabaković
· Sahib Muminagic
· [...]
· R. Efendić
dear dr. Dmitry,
It is good that you have found a connection with such an important teachings such as math! It is logical, exact and when it is known to use it the perfect base for scientific work in each area! And I know well although I medic I have always had excellent grades in mathematics and physics to me very expensive science!
I remain open to cooperation with you and my great desire to continue to collaborate!
Regards
Jasenko
Of course before that need more work on the training of new immunosuppressant, to enhance the possibility to overcome the immuno-biological barriers, improve clinical immunological laboratory tests for the purposes of xeno transplantation, microbiological to lie because most of these animals is infected, probably the new anti-infective drugs ..... etc etc!
Dear Dmitry,Thank you for your response! Of course you can call me just Jasenko, and I l can you simply you, Dmitry, which simplifies our communication!
Of course, and now I repeat that we are very pleased and honored to have communication with you and this name I expect to hear from you, when you come back the way!
Dear Dmitri, this is a very complex and interesting area, with which I was not much involved either-not have a lot of experience, so leave me time to think and I'll call you .....!
greeting
Jasenko
Dear Dmitry ,
this is a very complex and interesting area, with which I was not much involved either-not have a lot of experience, so leave me time to think and I'll call you .....!
greeting
Jasenko
Is xenotransplantation real future of organ transplants?. Available from: https://www.researchgate.net/post/Is_xenotransplantation_real_future_of_organ_transplants#view=58f4d33bed99e1141b372810 [accessed Apr 17, 2017].
My opinion is that they must seek and explore alternative sources of organs such as the xeno-transplantation, because the existing is not enough because the higher number of claimants organs from a donor! A large number of patients die on waiting lists, because they can not get the organ they say around 20-25%!
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 potentially using animals instead of people 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!
CLINICAL EXPERIENCE IN CANCER SUPPLY
Jasenko Karamehic
Founders of organ transplants are considered Alexis Carell and Charles Guthrie. The development of vascular anastomosis in the early 1900s allowed investigators to develop organ transplantation techniques. Carell and Gutrie, performed a replantation of the leg at the dog, and developed a known patch of graft technique to expand narrowed blood vessels. They also worked on heteroropic experimental transplantation. It is important to emphasize that the initial xeno and allotransplant functions only in a short period of time. In these pioneering beginnings, the most common causes of rejection were related to technical problems or substantial incompatibility. In view of this, the application of vascular anastomosis to organ replacement had to wait for the development of effective immunosuppressive therapy that occurred at least 50 years later.
When immunosuppressive agents became available in the early 1960s, human organs were still seldom available, leading the researcher to re-turn to the possibilities of xenotransplantation. In the early 60's, the Reemsthemian scientist succeeded in transplanting a 12-kid kidney series from the monkey chimpanzee to human recipients. The clinical development of these transplants was characterized by episodes of reduced renal function, which is analogous to acute cellular rejection. The transplant was associated with infection with 2 recipients and acute cell refs in 6 recipients. Some of the transplants functioned for months, most of which lasted 9 months. During this period, knowledge of transplantation immunology and immunosuppressive therapy was minimal. By using modern immune-suppressive therapies and antibiotics, these transplants could enjoy a long period of survival.
In the near past, baboon monkeys were transplanted to 2 human subjects with failure, that is by refusing them. Although liver donates from the baboon monkey finally died, it seemed that transplanted organs showed histological signs of rejection.
While the above results may be considered promising, there are serious limitations in the use of non-human mammals of the highest order as organ donors, even if ethical problems can be solved. Many top-level moms are too small, and large moms have not enough to meet the current need for the necessary organs. An important detail for xenotransplantation was observed in the 1990s when a pork retrovirus was detected. The problem associated with the risk of transmitting infection among species has resulted in many clinical studies in the field of xenotransplantation.
The current technology that could allow genetic engineering of certain animal species can not be applied to humans, and finally, even if the appropriate techniques were developed and solved social issues, the long period between the birth and maturity of the mammal of the highest order reject scientists from this approach!
Predložite izmjenu
Jasenko Karamehic
Bearing in mind the urgent need for organ donors and the problems associated with the use of non-human mammals of the highest order, many researchers focus on strategies that will overcome large immune hurdles when using the highest order mammalian as the organ donor. The animal that proved to be the most suitable for the purpose described above is the pig. Pigs have the appropriate size, and as far as they are known, they are physiologically compatible with humans. Pigs themselves possess relatively few types of microbiological agents that could be transmitted to humans. It is equally important to emphasize that pigs are bred in comparable comparable breeding periods. Finally, we have the technology available to genetically manipulate these animals, allowing us to make appropriate animal-donors be "planned" as providers with the greatest chance of successful transplanting to humans.
Unfortunately, science is faced with huge immune obstacles in transplanting animal organs to humans. Kidneys and heart transplants with non-high-risk mammals on genetically unmanaged people only functioned for a short period of time, if they were functioning at all, and transplant loss was probably caused by hyperacid refusal. Animal livers connected ex vivo to the circulation of patients with liver failure have managed to sustain the lives of several people. The "wear" of anti-contraceptive antibodies prevented hyperacid rejection of xenotransplantation in several reported cases.
Jasenko Karamehic
IMMUNOLOGICAL BARRIERS IN CANCER SUPPLY
To date, they do not give adequate answers to the questions of xenotransplantation, due to the many obstacles that arise from the response to the recipient's immune system. This response, which is largely higher than that of allotransplantation, ultimately results in the rejection of xenograft. There are several types of rejection of xenograft, which implies:
• Hyperactivity rejection
• Acute vascular rejection
• Celiac rejection
• Chronic rejection
CURRENT STATUS AND GUIDELINES IN CANCER SUPPLY
It is known that xenotransolants and xenotransplantation products are under regulatory authority of the FDA, the FDA has formulated the BRAMAC / Biological Response Modifiers Advisory Commitite as a current mechanism for open discussion on scientific, medical, ethical and social health issues related to xenotransplantation.
The FDA has developed a xenotransplantable action plan to create one approach to xenotransplantation regulation. This assumption implies regulating issues of public health and safety when it comes to xenotransplantation. In addition, this approach gives guidance to sponsors and researchers on the safety of clinical research and monitoring.
Occasionally, the FDA issues brochures that help researchers and sponsors
Interested in Xenotransplantation Research. These documents contain guidelines on the safety of xenotransplantation products and the course of clinical research, with particular reference to animal feed procurement and screening qualification recommendations, animal product testing as well as post-transplant monitoring and survival of animal transplant recipients. The FDA notifies and invites the public to comment and discussion on these documents, also organize mitigating and workgroups focused on xenon transplantation issues. Such gatherings help to exchange information and involve the public in xenon transplantation issues!
Jasenko Karamehic
FUTURE OF CANCER SUPPLY
It might be unusual for a manual that considers practical issues related to the practice of medical disciplines of transplantation and immunology should take into account such a hypothetical topic such as xenotransplantation. In all likelihood, the lack of human organ donors is such a serious problem that interest in xenotransplantation has significantly increased. With the advancement in developing methods that focus on processes:
1.) "Consumption" of human antibodies and on
2.) 2. Inhibition of the complement system, the problem of hyperacid rejection does not seem to be an insurmountable obstacle.
Rather, it could be said that acute vascular rejection, the cause of which is currently unclear, may now appear to be the main humoral barrier of xenotransplantation. If acute vascular rejection can be prevented by approaches that are useful in treating hyperacid rejection, then clinical xenotransplantation may become possible. If there was an accumulation, which would provide resistance to acute vascular rejection, then clinical transplantation could be further developed.
In the future, clinical xenotransplantation can achieve the desired goal of achieving prolonged graft survival, also using lessons from allotransplantation.
REFERENCES
1. Hickman R, Saunders SJ, Goodwin N, Terblance J. Perfusion of the isolated pig liver with human blood. J Surg Res, 1971; 11: 519-527.
2. Cooley DA, Gallman GL, Bloodwell RD, Nora JJ, Leachman RD, Human heart transplantation: experience with 12 cases. Am J Cardiol, 1968; 22: 804-810.
3. Abouna GM, Serrou B, Boehmig HG, Amemiya H, Martineau G. Long-term hepatic support by intermittent multi-species liver perfusions. Lancet, 1970; 2: 391-396.
4. Nalesnik MA, Fung JJ, Strazl TE, Demetris AJ. Pathology studies in two baboon to human liver xenograft cases. Transplant. Proc, 1994; (In press).
5. Auchincloss H Jr. Xenogeneic transplantation. Transplantation, 1988; 46: 1-20.
6. Reemtsma K. Xenotransplantation: a personal history. In: Xenograft 25, Hardy MA, (ed.) New York: Elsevier Science Publishers, 1989; 7-16.
7. Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, et al. The immunopathology of porcine livers perfused with the blood of humans with fulminant hepatic failure. Transplantation, 1994; 58: 1162-1171.
8. Welsh KI, Taube DH, Thick M, Palmer A, Stevens N, Binns RM. Human antibodies to pig determinants and their association with hyperacute rejection of xenografts. In: Xenotransplantation. The transplantation of organs and tissues between species, Cooper DKC, Kemp E, Reemtsma K, White DJG, (eds.). New York: Springer-Verlag, 1991; 501-510.
9. Czaplicki J, Blonska B, Relgia Z. The lack of hyperglycogenic xenogeneic heart transplant rejection in a human. J Heart Lung Transplant, 1992; 11: 393-398.
10. Jooste SV, Clovin RB, Winn HJ. The vascular bed as the primary target in the destruction of skin by antiserum. J Exp Med, 1981; 154: 1332-1341).
11. Starzl TE, Fung J, Tzakis A, et al. Baboon-to-human liver transplantation. Lancet. Jan 9 1993; 341 (8837): 65-71.
12. Rood PP, Cooper DK. Islet xenotransplantation: Are we really ready for clinical trials? Am J Transplant. Jun 2006; 6 (6): 1269-74.
13. Chatterjee DS. A controlled comparative study of the use of porcine xenograft in the treatment of partial skin thickness loss in an occupational health center. Curr Med Res Opin. 1978; 5 (9): 726-33.
14. Fink JS, Schumacher JM, Ellias SL, et al. Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transplant. Mar-Apr 2000; 9 (2): 273-8.
Predložite izmjenu
Transplantation of organs one of gratest achievement in history of medicine
Jasenko Karamehić1, Izet Mašić2, Zahida Drače1, Marina Delić-Šarac1, Djemo Subašić1
1Institute of Clinical Immunology KCUS
2Medical Faculty University of Sarajevo
Summary
The history of transplantation is a scientific journey describing the medical community's effort to understand how the human body works. Humans have long realized the possibilities which transplantation of organs and tissue provides. Throughout history people have always been intrigued by the possibilities of the transplantation of organs and tissues. In the 6th Century BC Indian surgeons described how to reconstruct facial wounds by transplanting skin from one place on the body to the other. During the middle age there were many references in historical medical literature of attempted blood transfusions as well as the transplantation of teeth. A skin transplant and a corneal transplant were reported in medical journals dating as far back as 1880. These early attempts were usually unsuccessful. Early in the twentieth century transplantation started to offer the promise of restored health and life. One of the exceptional medical advances of the twentieth century, organ transplantation has become a routine treatment for patients with organ failure which was a goal.
Key words: history of transplantation, organs, surgery, medical advances
Introduction
The meaning of the history of transplantation is important because the transplantation represents the beginning into advanced clinical medicine. In the 20th century we experienced an explosion in the discovery of human organisam and patology and transplantation is a new chapter in the reasurch and clinical application of discoveries for the benefit of the human being. (1)
The history of transplantation is a story about science whose application could not be fereseen at the start of the century. She is a result of years of cooperation between scientist and clinical personnel, both of which contributed to the salving of the puzzle, each in their respective fields. This is a fascinating story about modern surgery, which changed and will continue to change the final outcome of numerous conditions.(2)
The beggining of transplantation of organs
The idea of transplantation was always a big interest of medical researchers, but it is very hard to establish date when that idea was born. Many written documents from ancient Greek medicine expressed suspicious about the idea that transplantation of organs could become reality. Professional distinction between surgeons and doctors in ancient Greek was the main reason for that attitude (3).
Sushruta (6th century BC) was a renowned surgeon of ancient India, and the author of the book Sushruta Samhita. In his book, he described over 120 surgical instruments, 300 surgical procedures and classified human surgery into 8 categories.(4)That is the one of the oldest documents in Buddhist religion that deals with transplantation of organs. This material was about evaluation of level of knowledge and experience of surgeons who were capable to start transplantation. In these documents for the first time were mentioned medical sciences that should be involved in transplantation like, anatomy, physiology and pathology. Ancient Greek translated Samhita Sushruta and his work was analyzed by Hipokrat who often quoted him in his works.(5,6) Besides Sushruta ancient Greeks and Hipokrat were analyzing another great Hindu writer Kashmiri whose handwritings were about rhino plastic and surgery. Hipokrat himself was very involved in ethical and technical issues of transplantation. In his handwritings he comprehensively described surgical complications in operations of nose, ear, mouth etc.(7)
Egyptians overtook this method and well known Alexandria school was established. The greatest writers of that time were Hazes 924a.c. and Albucasis of Cordova 1013a.c. These famous Arabian writers highlights this era of progressive Arabian medicine.(8)
Transplantation through the centuries
One of the greatest school of European medicine in 15th century was Saleritan school. They mostly practiced reconstructive and war surgery. Under the influence of Saleritan School Emperor Frederick II (1215-1250) dynasty of Hohenstauff supported education of surgeons.(9) Crusade wars provided better communication between European, especially Italian cities, with those on Middle East and that was the reason why this school moved to Middle East so these doctors had lot of experience in reconstructive surgery and skin transplantation. One of the famous names in Saleritan School was Hugo Borgoggnoni who was a surgeon in Crusades. He was using skills of Arabian medicine for managing of war wounds and skin transplantation.(10)
Main development of reconstructive surgery took place in 15th and 16th century. One of the historian of that time Fazio Bartolomeo in his handwritings described great success of the school of the family Branca de Branca. After the death of the father and the son Branca, Baldassare Pavone took their place and improve methods in transplantation of skin grafts. He was very famous in Germany where he operated some German noble. He was awarded with Tevtonian cross for his accomplishment in field of war surgery.(11) In this period very important place had Hugo from Bologna 1547-1599 who worked on improvement of surgical techniques. He described all in his book "De Curtorum Chirurgia per inciosem" where he explains that transplantation of xenograft from one species to another is not possible also that transplantation from human to human is not possible too because of the different immunology constitution and specially is not possible from animal to human and vice versa.(12) That gave one epochal conclusion about possibility to transplant skin from one part of body to another on same person because there are no immunological differences.
In 16th and 17th century there were some great differences between French and English doctors and that led to total abandon of skin transplantation and decrease of interest in this kind of surgical treatment.(13,14)
Hunter and Thompson were famous surgeons in 18th century who spent ten year in India where they realized achievements of Indian doctors in fields of rhino plastic. That was big come back of skin transplantation in Europe. After affirmative results in 18th century Johann Dieffenbach published his experimental work on transplantation, regeneration of tissue and rhino plastic. He affirmed usage of free grafts which earlier methods disproved. Further more, Wolf and Thiersch achieved great results in infection prevention at skin transplantation. They realized that skin grafts don't need to contain subcutaneous tissue and that was their great achievement. In his experimental models Thiersch succeeded to prove that transplantation of skin from other species to human is not possible and transplant usually get rejected. Thirsch also gave an explanation for that graft rejection: reasons for graft rejection are in incompatibility between tissues.(15,16)
Development of blood transplantation from human to human also gave new hopes in field of organ transplantation. First doctor who made a machine for blood transplantation was English doctor James Blundell gynecologist and had a few cases of successful transfusion while delivering patients with excessive hemorrhaging. These cases bring lot of optimism between doctors of that time but at the same time post transfusion reactions gave certain insecurity (17) These negative reactions with temperature and fever resulted in abandon transfusion from animals to human and improve human to human transfusion techniques. In 1900 Erlich discovered that erythrocytes in blood transfusion, can act provocative in creating isohaemolisin or hemolytic antibodies. Landsteiner provided more detail explanation about who discovered mechanisms of that reaction and described these antibodies as anti E and anti B proving their bounding on erythrocytes of graft recipient.(18) For this discover Landsteiner was awarded with Nobel price for Medicine on the field of blood transfusion. That was a base for starting new era of transplantation. This improved understanding of basic immunological mechanisms and interactions of antibodies and need for further exploring of immunology was awakened. The result of that was discovery of role of lymphocytes cytotoxic antibodies and understanding of cross match reactions as base of histocompatibility of organs for transplantation.(19)
John Hunter 1728-1793 was a pioneer in the field of transplantation. He discovered that transplanted organ must have same conditions as in his natural environment as soon as possible. He described his experience in experiment with teeth, he transplanted teeth and discovered that transplanted organ needs supply of fresh blood in short period of time and that is condition for organ to survive. These principles are caped until today. Brown Sequard fallowed his steps and explored recovery of function of nervous system of transplanted organs. He improved discoveries of John Hunter and was rewarded by French Academy of Science. His experiments of isolation of organs form corps that he isolated and defibrinated in blood on 19 C degrees, 13 hours after dead. This kind of muscle preservation ensured that muscles have same answer on stimulation even after transplantation. In 20th century some of the postulates of Hunter theory were reborn.(20,21)
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.
Najrian J. S. Simmons L. R.: Tranplantation, Urban and Schwarzenberg, str. 3-22, 1972.
Starzl E. T.: Expierence in Renal Tranplantation, Saunders Comp. Str. 363-370, 1964.
Bošković S. Transplantacija organa i društvo, serija napisa o socio-medicinskim problemima transplantacije u društvu , "Oslobođenje" 15-30, januar 1981. godine.
Bošković S.: "Transplantacija bubrega", Poglavlje Istorija transplantacije , str. 15-27, 1987.
Karamehić J. i saradnici, "Transplantacija organa" Poglavlje Istorija transplantacije , str. 13-27, 2002.
Peer, LA: Transplantation of Tissues. Baltimore, Williams and Wilkins Company, pp. 25-29, 1955.
Carrel A: Results of the transplantation of blood vessels, organs and limbs. JAMA 51 : 1662-1667, 1908.
Carrel A: The transplantation of organs. New York Medical Journal, 25 April 1914, 839
Carrel A: La technique operatiore des anastomoses vascularies et la transplantation des visceres. Lyons Med 98: 589-864, 1902.
Holman, E: Protein sensitization in isoskinggrafting. Is the latter of practical value? Surg. Gynecol Obstet 38: 100-106, 1924.
Hume D, Merrill JP, Miller BF: Homologous transplantation of human kidneys. J Clin Invest31: 640, 1952.
Kolff WJ, Berk HThj: The artificial kidney: a dialyser with a great area. Acta Med Scan 117: 121-134, 1944.
Merril JP, Thorn GW, Walter CW et al.: The use of the artificial kidney. I TechniqueJ Clin Invest 29: 412, 1950.
Merril JP, Murray JE, Harrison JH et al.: Successful homotransplantation of the human kidney between identical twins. JAMA 160:277-282, 1956
Medawar PB: A second study of the behaviour and fate of skin homografts in rabbitsJ Anat 79:157-176, 1945.
Schwartz R, Stack J, Dameshek W: Effect of 6-mercaptopurine on primary and secondary immune responses. J Clin Invest 38: 1394-1403, 1959.
Murray JE, Merrill JP, Harrison JH et al.: Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 268: 1315-1323, 1963.
Rapaport FT, Dausset J: Ranks of donor-recipient histocompatibility for human transplantation. Science 167: 1260-1262, 1970.
Opelz G: Effect of HLA matching, blood transfusions and presensitization in cyclosporin-treated kidney transplant recipients. Transplant Proc 17: 2179, 1985.
Breimer ME, Brynger H, Rydberg L et al.: Transplantation of blood group A2 kidneys to O recipients. Biochemical and immunological studies of blood group A antigens in human kidneys. Transplant Proc 17: 2640, 1985.
Welch CS: A note of transplantation of the whole liver in dogs. Transplantation Bull 2:54, 1955.
Moore FD, Smith LL, Buranap TK et al.: One-stage homotransplantation of the liver following total hepatectomy in dogs. Transplantation Bull 6:103-107, 1959.
Starzl TE. Marchioro TI, Huntley RT et al.: Experimental and clinical homotransplantation of the liver. Ann NY Acad Sci 120: 739-765, 1964
Borel JF, Feurer C, Magnee C et al.: Effects of the new antilymphocytic peotide Cyclosporin A in animals. Immunology 32:1017, 1977.
Handschumacher RE, Harding MW, Rice J et al.. Cyclosporin: a specific cytosolic binding protein for cyclosporin A. Science 226:544, 1984.
Shaw BW, Gordon RD, Iwatsuki S, Starzl TE: Defining major risk factors in hepatic transplantation. Abstracts. American Society of Transplant Surgeons, p 33. May 1985.
Barnard CN: Human cardiac transplantation: an evaluation of the first two operations performed at the Groote Schuur Hospital, Cape Town. Am J Cardiol 22:584-596, 1982.
De Veies WC, Anderson JL: The clinical use of total artificial heart. N Engl J Med 310:273-278, 1984.
Szentpetery S, Morris JS, Hanrahan J et al.: Cardiac transplantation in the sixth decade of life. Transplantation Proc Vol XIX, Feb 1987, Proc XI International Congress of the Transplantation Society.
Hardy JD, Webb WR, Dalton ML et al.: Lung homotransplantation in man: report of the initial case. JAMA 186:1065-1074, 1963.
Starzl TE, Todo S, Fung J, Demetris AJ, Venkataraman R, Jain A: FK 506 for liver, kidney and pancreas transplantation. Lancet ii 1989; 1000-1004.
Delaney V, Nasir M, Brooklyn NJ. Liver transplantation: A challenge to nephrologists. Nephron, 1990; 55:353-360.
Storm TB. Therapeutic approach to organ transplantation. Nephrol Dial Transplant 1996; 11:1176-1181.
Cecka JM, Cho YW, Terasaki PI, Analysis of the UNOS scientific renal transplant registry at three years-early events affecting transplant success. Transplantation 1992;53:59-64.
Eleonor LR, Filney NL, Ravenscraft MD. Clinical aspects of renal transplantation in: Brenner and Rector WB Saunders 1 991:2361-2407.
Karamehić J, Dizdarević Z. et all. Klinička imunologija, Svjetlost, 2007.: 613-618.
Corresponding author:
Prof. Jasenko Karamehić MD, Clinical Center University of Sarajevo, Bosnia and Herzegovina, Institute of Immunology, Bolnička 25, tel: 00 387 33 297 304, [email protected]
I think that the concerns are great, but the scientific advances in basic medicine may direct the wave of research towards other innovations like implantable artificial kidneys and redesigning of the failed organs and structures through the regenerative medicine trials !!
I agree with you completely, you should direct all the strength to these examinations, if I had those bodies of redesigned religious, then the immune barrier would be minimal, which would be great!
But I also believe in discovering new immunosuppressants that will significantly improve transplant results and ease biological barriers!
As time progresses, and resources of the former are smaller, the asylum authority all the more, of course that is one of the options on which needs a lot of work is xenotransplantation!
The other option would be redesigned artificial organs, as this would avoid the immune biological barriers that are present in xenotransplantation!
And third natural resource as possible come home cells whose development also science must support!
Dear professor , in your opinion who are the greatest inventors in field of xenotransplantation?
Which animals were most challenging to take into account as transplant?
Yes you are right, not all the same antigenic activity!
The liver has a lower antigenic structure than other transplant!
3-5 years after liver transplantation occurs after statisckim the World Health Organization from 60 to 70 percent, as a relapse!
So far as candidates for donor organs closest human type per timber and similarities with human HLA types are the pig and monkey!
Answer dr.Dzananovic:
Yes replenished earlier reply, all previously depends what will be a strong antigenic response, whether the donor of a close relative or is this classic deceased donor transplantation, of course, where the antigenic response stronger proportional greater HLA diversity!
Xenotransplantation
Xeno-transplantation of living cells, tissue or organs from one species to another. Such cells or tissue are called xenografts and xenografts. Humana xenotransplantation offers a potential treatment for end-stage organ failure, which today is a major global problem. The dimensions of this problem as well as advances in immunotherapy, launched a great interest in the potential use of animals instead of people as organ suppliers. Researchers in this field have focused their efforts towards suppressing immune barrier that prevents the long-term survival of xenograft.
Ksenotransplantacion products must be alive. For example, human skin cells that grow out of the body, on the surface of a non-human cells and used for the reconstruction of the skin in humans can also be regarded as ksenotransplantacion product. This category was included in the definition of xenografts, as scientists consider the possible transmission of infection such procedures is similar to the transfer of infection in transplant live animal cells tissues or organs in the human donor.
In view of the urgent need for donor of organs and problems regarding the use of non-human primate, many researchers focus on strategies that will overcome major immunologic barriers using a primate as organ suppliers. An animal that has proved to be most suitable for the above-described A procedure is a pig. Pigs have the necessary size and how familiar are compatible with people. Pigs in themselves have relatively little biological agents that could be transmitted to humans.
Unfortunately, science is confronted with a large immunological obstacles in transplanting animal organs in humans. The kidneys and heart transplanted from a mammal other than the highest order are genetically non-manipulated people functioned only in a short period of time if they ever functioned, and the loss caused by the transplant probably hyperacute rejection. Animal liver connected "ex vivo" on cirukulaciju patients with liver failure have been able to sustain the lives of several people. "Lossy" anti davaočevih antibodies prevent the hiperaktuno rejection xenograft with few recorded cases.
There are several types of rejection ksengorafta which means
First hyperacute rejection
Second acute vascular rejection
Third cellular rejection and chronic rejection
The future of xenotransplantation
It might seem unusual to the manual that discusses the practical topics that relate to the practice of medical disciplines transplantation and immunology should consider such a hypothetical topic such as xenotransplantation. Apparently, the lack of human donor organs is such a serious problem that the interest in xenotransplantation drastically increased. With the advancement of methods that focus on processes:
1. "lossy" human antibody
Inhibition of the second komplementonog system
the problem of hyperacute rejection does not seem like an insurmountable obstacle. Rather it can be said that the acute vascular rejection whose cause is currently unclear now might seem like a major humoral barriers xenotransplantation. If acute vascular rejection can be prevented approaches that are useful in the treatment of hyperacute rejection then the clinical xenotransplantation could become possible. If it is found akomodacija, that would provide resistance to acute vascular rejection then the clinical xenotransplantation could be further developed.
In future clinical xenotransplantation can achieve the desired goal of achieving prolonged graft survival using and learning from the lessons of allotransplantation.
The disease in terminal condition being treated transplantation does not know the difference between age, race, gender, nationality or financial situation, there is good reason to refuse organ donation except myths and misunderstandings.
The role of the family is very important and there are substantial following features:
1. The family of the deceased asked to decide on organ donation of its direct members of the deceased at the time of the most serious crisis situations.
2nd A sense of disbelief, sadness, helplessness and guilt blurs their emitting state. Perhaps never as in this time of family need support environmental and health personnel.
3. At first glance it seems that maybe too optereiti family the question of organ donation. However, repeatedly has proven that family finds comfort when given the opportunity by donating organs allow life to other people.
It is important to believe that the donor wanted to help others and the belief that it will donate bring something noble and worthy. In contrast, the most common reason why the family does not want to consent to donation is distrust of healthcare workers regarding the distribution of authority, fear of large nagrđenja deceased delay the funeral and do not know the religious and cultural side of transplantation treatment. Talk about transplantation should be taken with caution bearing in mind the situation in which the family is, and respect that family feel accepting the death of their loved ones. The person who offers the option of organ donation should be familiar with the whole process.
The family must also have an opportunity to talk about donating and with other family members, possibly with a religious official. Before being offered the possibility of organ donation, it is necessary to ensure enough time for family understands and accepts that the death occurred. News of the death and seeking permission necessary is another "split". The family needs to get confidence that the body of the deceased to be treated with due care, dignity and respect, it is possible to see the body and there will be no additional costs.
The basis of generous giving without compensation embedded in Western civilization. Ethnicity transplantation, and voluntary anonymous donation, are the basis of organ donation.
"Donating does not require an award, it is its own reward"
It is believed to avoid injury and limiting are basic requirements for any use of human tissue which is ethically acceptable. These postulates are the center of some undefined but widely accepted demands for the respect of the human body and dignity. Although we have identified as avoiding or limiting injury basis for acceptance of the use of human tissue, there are other important considerations. For example, the consent of the one from which tissue is taken (patient, donor) or relative (after death) is significant. Consent is not the primary consideration. He especially can not justify injury: an example of how the killing or serious injury can not justify the wish of the victim.
Transplantation medicine is now conventional therapy for severe, terminal patients. Annually transplanted organs tens of thousands, of which the greatest need of the kidney but cadaveric transplants two thirds (70%) refers to a kidney transplant.
Successful organ transplants for years has been improving and is dependent on the development of many professions and scientific disciplines as well as the overall development of surgery, resuscitation, neurology, urology, immunology, transplantation immunology, biochemistry, nephrology, hemodialysis, pharmacology and others.
With a number of unresolved issues transplantacijke immunology remains the problem of organ donation to the ethical, religious and a functioning organizational sense. This difference can be reduced in various ways, but it is without doubt the most important detection, then the selection and evaluation of potential donors.
In relation to the cause of death and the circumstances under which it occurred, there are three types of cadaveric donor:
The first providers with brain death (donors with a beating heart, heart-beating donors.
2. Providers who died of cardiopulmonary jam (CPA donors)
Third providers without knocking the heart (non-beating heart donor donors HNB)
Detection of the donor is actually the first step in the explant-transplant process but it is still impossible to identify all potential donors. It is therefore necessary to further improve the profession and increase network coordinator. Of particular importance is to cultivate a genuine culture of giving within which each expressed the need to give their consent, the act of profound human solidarity and high social value.
The transplantation process begins and ends always in public - the citizens are the driving force and main benefactor. Donor cards are not used to register potential donors but serves as a means of creating public opinion, as a provocation to talk to family and outside it, in religious, school, academic and other communities and at all the information and create a positive atmosphere in public. This represents an indicative ethics - one that points to something not quite imperative ethic - something that commands and requires some duties.
6.2. A method after intake of organs and tissues
Once established death, a possible procedure of obtaining organs is carried out under sterile conditions in the operating room and in the hands of a qualified team of doctors. The body in this case will not be ugly now and will be treated with due respect.
Transplantation medicine in one country is successful if you planted a sufficient number of organs. The whole world is a big discrepancy between the growing need for organs and the number of organs at their disposal. Transplantation medicine is in some way become a victim of its own success. On the one hand a very rapid development of transplant medical science and practice on the other hand do not have sufficient authority to meet the growing needs.
The best results in the collection body in the world have been achieved in Spain in the last decade. Deceased organ donation has increased in the country of 14.2 donors per million inhabitants in 1989 to 31.5 in 1998. This is the result of well-planned and systematic organization poduzimanih measures "Spanish model", many invested their own efforts and motivation of health workers, health authorities, security services , transport, civil protection, judicial, forensic scientists, the media and above all the Spanish public and society. This is the only country in the world, in which the alloy waiting constantly decreasing. Especially in the country and highlights the great economic benefits of a transplantation medicine.
In 2000, noted the worrying situation. On average 14 people die every day due to lack of organs awaiting transplant until every 10 minutes to add a new name to the waiting list. Only about 30% of patients on waiting lists in Europe will have the chance to get a transplant, which means that many patients die waiting for an organ that is not will they save your life or significantly improve health.
Legislation Dealings
There are a number of legal options for the donation of organs in different countries, and there are even differences within countries. Differences between of individual states in the rate of organ donation even 10: 1. Only the legal and legal considerations, as they are crucial factors in the collection of bodies found in the professional engagement of health services, and not nepodjeljenoj support society. Seek permission from the family is the current trend, which follows most countries, regardless of their legal model that is in use.
• Today it is generally true that the model laid consent with the possibility of active exclusion model that the public accepts the best and this is the way the maximum respect for individual legal to own decision.
• Countries with such legal model (Belgium, Austria) have achieved higher rates of donation from other countries that do not have this model (Denmark, Netherlands, United Kingdom). Otherwise experience shows that every unnecessary talk about the legal model reduces the number of transplants.
• By the way, no country with a totalitarian regime anywhere in the world has never been an efficient system with a high degree of donating organs.
However, the first step is not the law but the creation of a healthy public opinion. The transplantation process always begins and ends in the public ends citizens are the main benefactors and the driving force. The health system must help in connecting donors and recipients, and healthcare workers have only served the role of professional and must never become protagonists.
Basic messages to the public that the transplant effective method of treatment and that brings good results to survive otherwise incurable patients and that this is the only way to save the lives of many terminal patients. It is worth postmortal donate their organs, because tomorrow they might need you or your relatives. The public must feel pride that in this part. Disclosure desire to donate allows the individual to express his sense of social responsibility and solidarity.
The dilemma of whether to undergo transplant or not, the recipient is mainly to keep the evaluation value in question ie. pondediranjem scale value. The risk is being offset by a mature assessment, so that the consent of the intervention can not possibly qualify as fatalistic or egotistical.
Is xenotransplantation is realistic as resource of organs for transplantation in the future. What should be done for improve for start in organ transplantation in close future.
Is there a real use of artificial organs in transplantation because they avoid immune barriers?
What is your opinion about the use of maternal cells in organ transplants in the near future?
Xenotransplantation comes in the future as one of the options, as a source of organs! However, the immunological barrier is high because it is a variety of specia and as such it must be a overcome-solve, amongst others with new immunosuppressants!
Also, the big problem is that a large number of animals are infected and this will stimulate immunosuppressive therapy, because it additionally weakens the immunity of the recipient ..... etc, etc., it is still a lot to work on this problem, which of course is not easy!
A very good question by Dr. Zecevic, I think that one of the options is a good idea to work on the creation of artificial organs, because in this way they can avoid easier immuno-biological barriers!
A very good question, also Dr. Zecevic, I think that one of the options is a good idea to work on the production of stem cells, as an allogenic translapation within the same species, because in this way, it is possible to avoid easier immuno-biological barriers that are present in xenotransplantation In the case of heterotranspantation in different species!
Stem cells
All questions are yours dr. Lamia, correctly set up and hit the essence of the problem, the lack of donors! According to the world health organization, only about 25% of donors are missing from hemodialysis, and many patients die and never expect to get a new kidney from a suitable donor!
- Badges
- Science topic