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Amanda J. Walne Tanya Bhagat Michael Kirwan Cyril Gitiaux Isabelle Desguerre Norma Leonard Elena Nogales Tom Vulliamy Inderjeet S. Dokal 《Haematologica》2013,98(3):334-338
Dyskeratosis congenita and its variants have overlapping phenotypes with many disorders including Coats plus, and their underlying pathology is thought to be one of defective telomere maintenance. Recently, biallelic CTC1 mutations have been described in patients with syndromes overlapping Coats plus. CTC1, STN1 and TEN1 are part of the telomere-capping complex involved in maintaining telomeric structural integrity. Based on phenotypic overlap we screened 73 genetically uncharacterized patients with dyskeratosis congenita and related bone marrow failure syndromes for mutations in this complex. Biallelic CTC1 mutations were identified in 6 patients but none in either STN1 or TEN1. We have expanded the phenotypic spectrum associated with CTC1 mutations and report that intracranial and retinal abnormalities are not a defining feature, as well as showing that the effect of these mutations on telomere length is variable. The study also demonstrates the lack of disease-causing mutations in other components of the telomere-capping complex. 相似文献
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Elena Menegola Francesca Di Renzo Francesca Metruccio Angelo Moretto Erminio Giavini 《Archives of toxicology》2013,87(11):1989-1997
The effect of mixtures of azole fungicides on development of postimplantation rat whole-embryos cultured in vitro has been tested. On the basis of bench mark dose (BMD) modeling of the in vitro effect in rat embryo, the potency of 7 azoles was determined and compared. Then, relative potency factors have been derived based on either the NOAEL or on the BMD curve. Alternatively, each compound was used as index compound (IC), and IC-equivalent concentrations have been calculated for each mixture. Expected effects of such IC-equivalent concentrations of the mixture were derived from the appropriate BMD curve. Test mixture includes the agrochemicals triadimefon and imazalil (MIX2) or triadimefon, imazalil, and the clinically used fluconazole (MIX3) at their previously determined no-effect concentration, corresponding to approximately a benchmark response of 5–10 %. Subsequently, we tested the effect of a mixture of the agrochemicals triadimefon, imazalil, triadimenol, cyproconazole, tebuconazole, and flusilazole (MIX6) at concentration levels derived from their established human acceptable daily intake. MIX6 was also added with fluconazole at concentration levels indicated as the minimum therapeutically effective plasmatic concentration (MIX7A) or ten times this level (MIX7B). Generally, the experimental response was higher than the estimated one, by a factor of 2–6. Our data suggest that it is in principle correct to assume that azoles act as teratogens via a common mode of action and therefore should be grouped together for risk assessment. The synergistic effect needs to be confirmed with more combinations of concentrations/compounds in vitro and with specific in vivo experiments. 相似文献
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Luca Filippi Chiara Poggi Elena Gozzini Rosanna Meleleo Lorenzo Mirabile Patrizio Fiorini 《Acta paediatrica (Oslo, Norway : 1992)》2009,98(5):906-909
Candidiasis is relatively frequent in neonatal and pediatric intensive care units (ICUs), particularly in preterm infants less than 28 weeks of gestational age. Neonatal candidiasis shows high mortality and is often associated to poor neurodevelopmental prognosis in survivor patients. Amphotericin B and fluconazole are the first choice drugs for the treatment of neonatal candidiasis. Caspofungin is an alternative antifungal agent, which is recommended for invasive candidiasis in adults, but has been poorly experienced in neonates and infants as far as now. We report the first two infants with Candida liver abscesses treated with caspofungin. In the first infant bloodstream and liver lesions were cleared by combination therapy with fluconazole, liposomal amphotericin and caspofungin, while in the second one by caspofungin alone.
Conclusion: Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule. 相似文献
Conclusion: Our observations confirm the efficacy and tolerability of caspofungin in the treatment of neonatal candidiasis refractory to conventional antifungal drugs. More extensive data are recommended in order to asses a specific neonatal schedule. 相似文献
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