The translational activation of dormant tissue-type plasminogen activator mRNA during meiotic maturation of mouse oocytes is accompanied by elongation of its 3'-poly(A) tract. Injected RNA fragments that correspond to part of the 3'-untranslated region (3'UTR) of this mRNA are also subject to regulated polyadenylation. Chimeric mRNAs containing part of this 3'UTR are polyadenylated and translated following resumption of meiosis. Polyadenylation and translation of chimeric mRNAs require both specific sequences in the 3'UTR and the canonical 3'-processing signal AAUAAA. Injection of 3'-blocked mRNAs and in vitro polyadenylated mRNAs shows that the presence of a long poly(A) tract is necessary and sufficient for translation. These results establish a role for regulated polyadenylation in the post-transcriptional control of gene expression.

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The aim of this study was to investigate whether apoptosis contributes to nephrotoxicity caused by amphotericin B (AmB). By detecting apoptosis-specific DNA fragmentation, it is demonstrated that proximal tubular cells (LLC-PK 1 ) and medullary interstitial cells (RMIC) respond with programmed cell death when treated with therapeutic doses of AmB. Concomitant application of AmB and recombinant human insulin-like growth factor-1 (rhIGF-1), a known antiapoptotic agent, abrogated apoptosis in vitro. To validate that the observed apoptotic effects on renal tissue culture cells are applicable to an in vivo setting, an animal model was used for verification. Therefore, Sprague-Dawley rats were treated with AmB. The drug caused hypokalemia, decreased weight gain, loss of renal concentrating ability, and dehydration in a dose-dependent fashion. Microscopic examination of renal tissue sections revealed apoptotic alterations predominantly in proximal and distal tubular epithelial cells. To verify that the observed clinical side effects were linked to apoptosis, rhIGF-1 was applied concomitantly with AmB. In all animals, rhIGF-1 prevented the above-mentioned clinical side effects. Moreover, significantly reduced apoptosis was observed in renal tissue sections of these animals, indicating the relevance of apoptosis in nephrotoxicity. This is the first report to demonstrate that AmB induces apoptosis in the rat kidney in a dose-dependent fashion. The incidence of apoptosis correlates with renal toxicity and can be abrogated by concomitant treatment with rhIGF-1.

Objective: As effects of glucocorticoids differ with respect to preparation, dose and duration, we hypothesized that a postnatal regimen of a low-dose, short-course betamethasone treatment had comparable efficacy and a better safety profile compared to the conventional high-dose, dexamethasone.Study Design: To test our hypothesis, we selected premature neonates with a birth weightp1000 g and a gestational age p29 weeks who were ventilated >10 postnatal days with an FiO 2 >0.4 and no ability to wean mechanical support for X3 consecutive days. These neonates either received twice daily dexamethasone 0.25 mg kg À1 per dose intravenously for 3 days tapered to 0.125 mg kg À1 per dose for 4 days (June 1999 to December 2000) or betamethasone 0.125 mg kg À1 per day intramuscularly once per day for 3 days (January 2001 to December 2002). Result:We found a significant reduction in FiO 2 after 3 days in both glucocorticoid treatment groups. There were no significant differences between the two treatment groups in the clinical parameters including decrease in FiO 2 , oxygenation index, mean airway pressure and percent extubation. Duration of ventilation, number of oxygen days and length of hospital stay were comparable in the two groups. Of particular interest, the betamethasone group showed fewer adverse effects, such as poor weight gain and high blood glucose, than the dexamethasone group.Conclusion: A short course of low-dose betamethasone has comparable efficacy and seemingly a better short-term safety profile compared to conventional dexamethasone treatment.