Bone therapy

Very active researches concern this family of drug targets in the fields of cancer, angiogenesis and bone therapy. Dibotermin alfa (rhBMP2), a recombinant form of BMP is accepted for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary nail fixation in patients in whom there is a substantial risk of non-union. Three platforms of TGF-(3... 

Poiyoief ins. Polyethylene can be phosphorylated with phosphorus trichloride and oxygen by a free-radical chain reaction (118,149-151). Side reactions include separate oxidation of the phosphorus trichloride and of the polymer. Hydrolysis gives phosphonic acid structures, which can impart flame retardancy and improved adhesion to surfaces. These materials have been explored for dental and bone therapy applications but no commercial use is known. 

Figure 13.9. Commonly used bone grafts in clinical bone therapy.

Pneumogstis carini pneumonia (PCP), the most common of the opportunistic infections, occurs in more than 80% of AIDS patients (13). Toxoplasmosis, a proto2oan infection of the central nervous system, is activated in AIDS patients when the 004 count drops and severe impairment of ceU-mediated immunity occurs. Typically, patients have a mass lesion(s) in the brain. These mass lesions usually respond well to therapy and can disappear completely. Fungal infections, such as CTyptococcalmeningitis, are extremely common in AIDS patients, and Histop/asma capsulatum appears when ceU-mediated immunity has been destroyed by the HIV vims, leading to widespread infection of the lungs, Hver, spleen, lymph nodes, and bone marrow. AIDS patients are particularly susceptible to bacteremia caused by nontyphoidal strains of Salmonella. Bacteremia may be cleared by using antibiotic therapy. 

Adverse side effects of gold treatments include stomatitis, rash, and proteinuria. Complete blood counts and urinalysis should be performed before each or every other injection of gold compounds. Pmritic skin rash and stomatitis are more common adverse effects that may resolve, if therapy is withheld for a few weeks and then restarted cautiously at a lower dose. Oral gold causes less mucocutaneous, bone marrow, and renal toxicity than injectable gold, but more diarrhea and other gastrointestinal reactions appear. 

Various estimations indicate that nearly twenty million women in America suffer osteoporotic problems. The physiological changes that take place are certainly forms of aging. In one five-year study where ERT compliance was carefully monitored, the bone mineral density increased regardless of the length of treatment or the patient s age when therapy commenced (69). 

Dactinomycin, an antineoplastic dmg, was discovered in 1943 and is made in rather pure form by StreptomjcesparvuUus. Dactinomycin has some bacteriostatic antibacterial and antifungal activity, but high toxicity limits its use to antineoplastic therapy. It may be used alone or with other antineoplastics, with or without surgery and synergistic x-ray therapy. Dose limiting bone marrow toxicity may result in low white cell and platelet count. Intestinal mucosal damage also occurs. Reviews of more detailed chemotherapeutic information are available (217—222). 

Trifluridine, C2qH22F2N20, (5-trifluoromethyl-2 -deoxyuridine [70-00-8] F TdU, 14) was first prepared (30) in 1962. It is used for topical therapy of herpes vims-infected eyes. It is especially usefiil for treating infections that are resistant to IdU therapy. Like IdU, trifluridine is incorporated into DNA in place of thymidine in both infected and uninfected cells. But it is 10 times more potent than IdU against herpes keratitis in rabbits and 10 times more soluble in water. Trifluridine is also usefiil in treating human cytomegalovims (HCMV), but its toxicity to bone marrow may limit its clinical use. 

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

Due to the rapid appearance of resistance, 5FC is only used as a combination partner for the intensive therapy of established severe fungal infections caused by Candida spp., Cryptococcus neoformans and Aspergillus sp. Anorexia, nausea, vomiting, diarrhoea and or abdominal pain occur in 6% of the patients. Of greater concern is the potential for bone marrow depression (seen in 5% of the patients, all with elevated 5FC levels). 

Cellular therapies in transplantation and cancer are based on specific cells separated or sorted from human blood, bone marrow, or cord blood by means of their specific cell surface markers or cell differentiation antigens, e.g., CD3, CD4, CD8, CD 14, CD 19, and CD34. For example, the CD34+ stem cells, especially those derived from human embryos, have the capacity to differentiate in culture to generate different somatic cells, e.g., liver cells, heart cells, neurons, etc. This exploding field of research is now termed regenerative medicine. 

Systemic treatment of 13-cis retinoic acid frequently leads to cheilitis and eye irritations (e.g., unspecific cornea inflammation). Also other symptoms such as headache, pruritus, alopecia, pains of joints and bone, and exostosis formation have been reported. Notably, an increase of very low density lipoproteins and triglycerides accompanied by a decrease of the high density lipoproteins has been reported in 10-20% of treated patients. Transiently, liver function markers can increase during oral retinoid therapy. Etretinate causes the side effects of 13-cis retinoid acid at lower doses. In addition to this, generalized edema and centrilobulary toxic liver cell necrosis have been observed. 

This illness is mainly characterized by an age-related bone loss. The detection of osteocalcin in bone was the starting point for a series of studies on the role of vitamin K-dependent proteins in bone development and maintenance and on possible supplemantation therapies. Epidemiologic studies found differences in the risk of hip fractures depending on the dietary vitamin K... 

An additive nephrotoxicity develops when pentamidine isethionate is administered with other nephrotoxic drugs (eg, aminoglycosides, vancomycin, or amphotericin B). An additive bone marrow depression occurs when the drug is administered with antineoplastic drugs or when the patient lias received radiation therapy recently. 

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