CYCLOSPORINE A IMMUNOSUPPRESSION IN SHEEP WITH RESPONSE ENHANCEMENT BY CONCOMITANT KETOCONAZOLE

1. The pharmacokinetics of a single dose of Cyclosporine A (CsA) administered to sheep by intravenous (i.v.) route were examined. 2. Concomitant administration of ketoconazole was found to increase the area under the blood CsA concentration-time curve (AUC) and was effective when adminstered by the oral or intraperitoneal route. 3. The effects of CsA and ketoconazole on the immune system of sheep were also assessed. 4. A single dose of CsA 5mg/kg resulted in abrogation of in vitro lymphocyte function manifest at 24h after injection of CsA. Normal responsiveness recovered in 48-72h. Numbers of T lymphocytes in peripheral blood were elevated transiently at 48h although no other significant alteration in lymphocyte subsets was observed with this treatment. 5. Concomitant ketoconazole administration enhanced the CsA-induced suppression of in vitro lymphocyte responses. Blood levels of CsA (AUC values to 24h) were significantly elevated with concomitant ketoconazole administration and depression of lymphocyte responses to mitogens were also significantly enhanced. An increase in the proportion of T4 positive cells in the blood was observed at 48h and at 7 days after administration of CsA with ketoconazole. 6. These findings indicate that CsA effectively abrogates immunocompetence in the sheep and this immunosuppressive effect is enhanced by concomitant administration of ketoconazole.     

Therapy-induced drug resistance in a human leukemia line (LALW-2). A clinically relevant model

A human leukemic T-cell line, LALW-2, established by xenografting in nude mice, has been maintained through 14 serial passages. The cells display consistent morphologic features, immunophenotype, and karyotypic aberrations (including an 11;14 translocation) and exhibit rearrangement of the T-cell receptor beta-chain gene. The growth rate of LALW-2 xenografts was differentially affected by drugs administered to host mice, the cells being resistant to cytotoxic agents (particularly methotrexate and doxorubicin) used in treatment of the donor patient. In short-term in vitro culture, LALW-2 cells exhibited extreme resistance to methotrexate and were also resistant to vincristine, vinblastine, dactinomycin, and doxorubicin. The findings differ from those obtained with laboratory-derived methotrexate or multidrug-resistant cell lines. The response of LALW-2 cells, in both the nude mouse model and in vitro, is consistent with acquisition of drug-resistance as a result of clinical treatment.     

抗寄生虫药物硝硫氰胺类似物的合成

本文报道52个硝硫氰胺的衍化物,经对小鼠抗日本血吸虫筛选结果表明,其中8个化合物有抗日本血吸虫作用。化合物23对家兔血吸虫病的疗效较硝硫氰胺明显为高。对其中的6个化合物经棉鼠丝虫病实验治疗,发现化合物2和26有抗丝虫病作用,化合物26对微丝蚴和成虫的杀灭作用,不亚于海群生。药理研究正在进行中。     

Tumour Lysis Following Hydrocortisone Prior to a Blood Product Transfusion in T-Cell Acute Lymphoblastic Leukaemia

The acute tumour lysis syndrome is a well recognised complication of chemotherapy for lymphoid malignancies. There are few reports, however, of this complication after corticosteroid therapy alone. We report a case of T-cell acute lymphoblastic leukaemia who developed the biochemical picture of tumour lysis after two doses of hydrocortisone given prior to platelet transfusion. Prophylactic corticosteroids prior to blood product infusion should be reserved for patients who have experienced febrile or allergic reactions in the past and it is suggested that they should only be administered to patients with active lymphoid malignancies with due caution.