Bone rejection

Dog repeUents available commercially in the 1990s have been generally unsuccessful in laboratory tests. Por example, lithium chloride treatments were usually rejected immediately with no ingestion, and bone oil treatments that contained up to 0.1% of the active ingredient were stiH consumed (93). Oleoresin capsicum [8023-77-6], the essence of red pepper, did have an extended effect on coyotes, even though the deer repeUents mentioned above were attractive to coyotes (93). Although a capsicum-base aerosol repeUent has been described as potentially harmful (94), pepper spray is commercially available in the United States to repel humans, as is Mace. 

Figure 8. U concentration profiles measured using ICP-MS for bones from Boxgrove. These bones show characteristic leached profiles (compare with Fig. 5), and are rejected as unsuitable for dating. [Used by permission of Elsevier Science, from Pike et al. (2002), Geochim Cosmochim Acta, Vol. 66, Fig. 5f, p. 4280.]...

Hydroxyapatite constitutes -65% of human bone by weight. There is another 18% collagen fiber which makes the bone flexible and more durable. Then, there is -10% genetic tissue (mostly living bone cells). This tissue carries the genetic code of the person or animal and unless it is in a denatured form, which also kills the bone, it is likely to be rejected in the body as a bone graft. Therefore, it is impossible to successfully implant living bone even from closely related donors. The remainder of bone is composed of capillaries, nerves, and so on. 

Levy RB, Murphy WJ Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25 + regulatory T cells. Proc Natl Acad Sci USA 2006 103 5460-5465. 

Adult bone marrow MSCs, which are easy to manipulate genetically and weakly immunogenic, represent another potential source of allogeneic stem cells [61]. Allogeneic MSCs actually inhibit T cells in culture [62], and several in vivo studies have achieved good engraftment of allogeneic MSCs without rejection [61]. 

Mycophenolate mofetil is used together with cyclosporine and corticosteroids for the prophylaxis of acute organ rejection in patients undergoing allogeneic renal, or hepatic transplants. Compared with azathioprine it is more lymphocyte-specific and is associated with less bone marrow suppression, fewer opportunistic infections and lower incidence of acute rejection. More recently, the salt mycophenolate sodium has also been introduced. Mycophenolate mofetil is rapidly hydrolyzed to mycopheno-lic acid, its active metabolite. Mycophenolic acid is a reversible noncompetitive inhibitor of inosine monophosphate dehydrogenase, an important enzyme for the de novo synthesis of purines. As lymphocytes have little or no salvage pathway for purine... 

Muromonab-(CD3) Orthoclone OKT3) is a mouse monoclonal antibody that is a purified IgG. It is used for the prevention of acute allograft rejection in kidney and hepatic transplants and as prophylaxis in cardiac transplantation. It is also used to deplete T cells in marrow from donors before bone marrow transplantation. 

Unlabeled Uses Prevention of organ rejection in patients receiving allogeneic bone marrow, heart, pancreas, pancreatic island cell, or small-bowel transplant, treatment of autoimmune disease, severe recalcitrant psoriasis... 

The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases. They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation. 

It is a cyclic polypeptide with 11 amino acids. It selectively inhibits T-lymphocytes proliferation, IL-2 and other cytokine production. It is the most effective drug for prevention and treatment of graft rejection reaction. It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermato-myositis, bronchial asthma and certain other autoimmune diseases. 

G. Other applications Other possible uses of Orthoclone OKT3 are for prophylaxis and treatment of acute graft-versus-host disease (as an adjunct with allogeneic bone marrow transplantation) treatment of rejection after lung transplantation prophylaxis and treatment of rejection... 

Azathioprine is a cytotoxic inhibitor of purine synthesis effective for the control of tissue rejection in organ transplantation. It is also used in the treatment of autoimmune diseases. Its biologically active metabolite, mercaptopurine, is an inhibitor of DNA synthesis. Mercaptopurine undergoes further metabolism to the active antitumour and immunosuppressive thioinosinic acid. This inhibits the conversion of purines to the corresponding phosphoribosyl-5 phosphates and hypoxanthine to inosinic acid, leading to inhibition of cell division and this is the mechanism of the immunosuppression by azathioprine and mercaptopurine. Humans are more sensitive than other species to the toxic effects of the thiopurines, in particular those involving the haematopoietic system. The major limiting toxicity of the thiopurines is bone marrow suppression, with leucopenia and thrombocytopenia. Liver toxicity is another common toxic effect. 

In the management of transplants, ALG and monoclonal antibodies can be used in the induction of immunosuppression, in the treatment of initial rejection, and in the treatment of steroid-resistant rejection. There has been some success in the use of ALG and ATG plus cyclosporine to prepare recipients for bone marrow transplantation. In this procedure, the recipient is treated with ALG or ATG in large doses for 7-10 days prior to transplantation of bone marrow cells from the donor. Residual ALG appears to destroy the T cells in the donor marrow graft, and the probability of severe graft-versus-host syndrome is reduced. 

The role of minor histocompatibility antigens in GVHD and rejection A minireview Goulmy, E., Voogt, P., van Els, C., de Bueger, M., van Rood, J. (1991). Bone Marrow Transplant, 7 Suppl 1 49-51. 

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