Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above the therapeutic dose in humans). Lymphoplasmacytic thyroiditis was present in 20% of females given 25 mg/kg and in 20 and 47% of males and females given 50 mg/kg, respectively. Thyroiditis was still present 4 wk following drug withdrawal. Thyroiditis was characterized by glandular enlargement, follicular epithelial hyperplasia and degeneration, colloid depletion, and interstitial infiltrates of lymphocytes and plasma cells. Drug-related changes in other tissues included lymphoid depletion of T-cell regions of thymus, spleen, and lymph nodes; bronchiolization of alveolar ducts with accumulation of mucus and foamy macrophages; testicular atrophy with sperm granulomas; dermoepidermal lymphocytic infiltrates with ulceration and alopecia; and hepatocytomegaly.
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PMID:Subchronic toxicity of pentostatin in Wistar rats. 789 80

We have previously reported that weekly administration of the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), reduces the incidence of insulin-dependent diabetes mellitus (IDDM) in the BB Wistar rat, and this effect is likely due to immunosuppression by dCF. In the present study, we examined the effect of altering the dose and scheduling of dCF on prevention of IDDM in the BB rat. When rats were treated from day 25 of age with 2.5, 4, or 10 mg of dCF/kg/week, the percentage of diabetes-free animals at 120 days of age was 40, 60, and 80% respectively, compared with 10% for control animals, demonstrating increased protection against IDDM with increased dCF dose. Histological assessment of the pancreata from animals that became diabetic revealed a marked mononuclear infiltrate and a loss of positive staining for beta cell granules. In contrast, pancreata from animals that remained diabetes-free appeared normal. Protection against IDDM by dCF was time dependent and only occurred if treatments were initiated by day 30 of age. In addition, the protective effect persisted after drug withdrawal. Further studies are required to determine the optimum duration of therapy with dCF to prevent IDDM and to examine the immunological mechanism responsible for this effect.
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PMID:Immunotherapy for insulin-dependent diabetes mellitus in the "BB" rat. 921 88