Organ transplant rejection

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Corticosteroids also exert inhibitory effects on the overall immune process. These drugs impair the function of the leukocytes responsible for antibody production and destruction of foreign cells. As a result, corticosteroids are also used therapeutically in the prevention of organ transplant rejection. 

Aging (skin and other tissues), myocardial infarct or stroke, inflammation, rheumatoid arthritis, atherosclerosis, pulmonary disorders (asthma and chronic obstructive pulmonary diseases), radiation injury, organ transplant rejection, psoriasis, hypertension, AIDS, multiple types of cancer, neuro-degenerative diseases (Parkinson s), diabetes, muscular dystrophy... 

Unlabeled Uses Adrenocortical, bladder, cervical, endometrial, prostatic, testicular carcinomas Ewing s sarcoma multiple sclerosis non-small cell, small cell lung cancer organ transplant rejection osteosarcoma ovarian germ cell, primary brain, trophoblastic tumors rheumatoid arthritis soft tissue sarcomas systemic dermato-myositis systemic lupus erythematosus Wilms tumor... 

Prevention of organ transplant rejection PO Loading dose 6 mg. Maintenance 2 mg/day. 

Mechanism of Action An immunologic agent that inhibits T-lymphocyte activation by binding to intracellular proteins, forming a complex, and inhibiting phosphatase activity. Therapeutic Effect Suppresses the immunologically mediated inflammatory response prevents organ transplant rejection. 

Based on the results from these three trials, BioCryst has initiated a multicenter Phase III trial for the treatment of CTCL, as well as a large, multicenter Phase II trial for psoriasis. In addition to the two clinical trials using the topical formulation, a Phase I clinical trial in CTCL and T-cell lymphoma/leukemia has begun using an oral formulation of BCX-34. In the future, a number of other T-cell mediated diseases or processes are possible targets for BCX-34, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and organ transplant rejection. 

In measuring cyclosporin A (a treatment for skin and organ transplant rejection) by HPLC, according to a method derived from that of internal standard, the following procedure is employed. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Understanding the molecular basis of immune responses has allowed the definition of mechanisms by which cellular function is altered by local hormones or autacoids in infections, cancer, autoimmune diseases, and organ transplant rejection. These processes present targets for therapeutic intervention. 

Immunosuppression or enhancement can be associated with two distinct groups (1) Drugs intended to modulate immune function for therapeutic purposes (e.g. to prevent organ transplant rejection) where adverse immunosuppression can be considered exaggerated pharmacodynamics. (2) Drugs not intended to affect immune function but cause immunotoxicity due, for instance, to necrosis or apoptosis of immune cells or interaction with cellular receptors shared by... 

Sirohmus is used for the prophylaxis of organ transplant rejection in combination with a calcineurin inhibitor and glucocorticoid. In patients at high risk for nephrotoxicity it has been combined with glucocorticoids and mycophenolate to avoid permanent renal damage (Kahan and Camardo, 2001). 

Wilde Ml, Goa KL (1996) Muromonab CD3 a reappraisal of its pharmacology and use as prophylaxis of solid organ transplant rejection. Drugs 51 865-894. 

Cyclosporin A/Neoral / Novartis / immunosuppressant prophylaxis for organ transplant rejection... 

The inflammatory response is initiated by stimuli released from sites of tissue injury that results in the expression of selectins on the endothelial layer. These selectins (E(endothelial)-selectin and P(platelet)-selectin) function through recognition of oligosaccharides on the opposing leukocyte cell surface [194]. This interaction eventually weakly tethers the leukocyte to the endothelial layer, at which point integrin binding events lead to firm adhesion and extravasation of the leukocyte into the tissue. In certain disease processes, excessive leukoc)4e infiltration becomes deleterious to the body, and inhibitors of this process are desirable. Rheumatoid arthritis, asthma, organ transplant rejection, and reperfusion injury are just a few of the cases in which these events occur [27]. 

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