Tumour necrosis factor-alpha (TNF-alpha) is related to some other factors in addition to being the essential cytokine of the sepsis which results from Candida infections. In our study, we investigated serum TNF-alpha levels, measured by enzyme-linked immunosorbent assay (ELISA), and platelet-activating factor (PAF)-like activity, measured by high-pressure liquid chromatography (HPLC) of the mice infected with Candida species. The PAF antagonist, ginkgolide BN 52021 was used to evaluate the possible interaction between TNF-alpha and PAF. The average TNF-alpha levels were found to be 396, 489, 699 and 803 pg ml(-1) on the 4th, 5th, 6th and 19th days of Candida albicans infection, respectively (P<0.05). There was no statistically significant difference between the serum TNF-alpha levels of the groups infected with other Candida species, such as C. kefyr, C. krusei and C. tropicalis (P>0.05). Serum TNF-alpha levels were found to be more significantly different in mice with C. albicans infection that were injected with PAF antagonists on the 6th day (23 pg ml(-1)). It was therefore thought that PAF antagonists have an inhibitory effect on TNF-alpha production. No significant difference was found between PAF levels in the three groups: healthy control mice, C. albicans-infected mice and C. albicans-infected mice given PAF antagonists (466 milli-absorbance unit (mAU), 475 mAU and 329 mAU, respectively). It was noticed that the positive interaction between PAF and TNF-alpha was not important after the first 4 days of the infection had passed.

Methotrexate (MTX) is the chemotherapeutic for which the serum levels can be detected. If the MTX level is detected in time, high toxicity risk can be decreased. In this study, intermediate doses of MTX (1 g/m2) infusions are administered to B-cell non-Hodgkin lymphoma patients between 3 and 13 years old. The toxicity of MTX in accordance with serum levels and the toxicity of other combined drugs are investigated. Blood samples were collected consecutively, and MTX levels were detected by high-performance liquid chromatography. When hematological, gastrointestinal, and renal toxicity scores were compared with the 24-h serum levels of MTX, they showed a significant positive correlation. Hematological toxicity scores increased by Ifosfamide, Etoposide, and Cytarabine combined with MTX without altering the serum levels. Antibiotic combination with MTX has no effect on the toxicity scores. In conclusion, if MTX is combined with other myelosuppressive, hepatotoxic, and nephrotoxic drugs, the measurement of MTX serum levels alone is not a sufficient parameter to show the toxicity.

Renal ischaemia-reperfusion (I/R) is a pathological condition occurring frequently after transplantation and acute renal failure. A mediator thought to play a role in the disturbed haemodynamics of I/R is platelet activating factor (PAF). We studied endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) vasorelaxant responses and the effect of BN 52021, a PAF antagonist, in the isolated perfused rabbit kidney after in vivo and in vitro I/R. Anaesthetized rabbits underwent right nephrectomy and 1 h left renal artery clamping followed by 30min reperfusion with blood. In another group, kidneys were isolated and, after transferral to the perfusion system, the perfusion pump was turned off for 1 h, followed by 30min reperfusion with Krebs' solution. BN 52021 or its vehicle dimethylsulphoxide (DMSO) was administered 20min before left renal artery occlusion or turning off the pump. Although in vitro I/R did not influence ACh-induced responses, in vivo I/R caused a decrease which was prevented by BN 52021. SNP-induced responses did not change in in vitro I/R and decreased only at lower concentrations in in vivo I/R, whereby pretreatment with BN 52021 did not offer any protection. It is concluded that in vivo I/R diminishes ACh-induced endothelium-dependent vasodilation, possibly via PAF and blood components, whereas SNP-induced endothelium-independent vasodilation was not altered by in vivo and in vitro ischaemia in the isolated rabbit kidney.

Poster Session II: Therapeutic Drug Monitoring/Immunosuppressive Drugs Wednesday, September 6, 1995: PDF Only