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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.

A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : The 5-lipoxygenase products, especially sulfidopeptide leukotrienes take an important role in the pathogenesis of asthma. The effects of two selective 5-lipoxygenase inhibitors, acetohydroxamic acid derivative BWA 4C and a naphtokinon derivative CGS 8515, were investigated for their effect on antigen-induced contraction in ovalbumin sensitized guinea-pig isolated tracheal tissues. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : The study included 15 male guinea pigs. They were actively sensitized by the Modified Andersson Method, including two standard 0.5 mL injections of a solution containing 20 µg ovalbumin and 50 mg aluminium hydroxide in saline on day 0 and day 14. Twenty-one to 27 days after the injection of ovalbumin, the tracheal rings from sensitized guinea pigs were exposed to antigen, and the possible inhibitor effects of 5-lipoxygenase inhibitors on the antigen-induced contraction were examined in water-jacketed tissue baths containing Krebs buffer. R Re es su ul lt ts s: : Both BWA 4C and CGS 8515 significantly reduced antigen-induced tracheal contraction compared to control groups. C Co on nc cl lu us si io on n: : As both CGS 8515 and BWA 4C inhibit antigen induced tracheal smooth muscle contractions, they may take an important role in the treatment of asthma and related inflammatory events.

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.

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