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排序方式: 共有602条查询结果,搜索用时 46 毫秒
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Tomáš Šimůnek Martin Štěrba Olga Popelová Michaela Adamcová Radomír Hrdina Vladimír Geršl 《Pharmacological reports : PR》2009,61(1):154-171
The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection. 相似文献
3.
Sakashita N Ando Y Obayashi K Terazaki H Yamashita T Takei M Kinjo M Takahashi K 《Virchows Archiv : an international journal of pathology》2000,436(4):345-350
We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin
(ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary
incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made
on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of
septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition.
The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys
compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent,
particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49
years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR–amyloid
deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially
around microvessels. These characteristic patterns of systemic amyloid deposition and distinct clinical manifestations, especially
in the cardiovascular system, are considered to be a characteristic feature of ATTR Ser50Ile amyloidosis.
Received: 31 August 1999 / Accepted: 19 October 1999 相似文献
4.
Covalent modifications of histones integrate intracellular and extracellular cues to regulate the genome. H3 Lys 9 methylation (H3K9me) can direct heterochromatin formation and DNA methylation, while phosphorylation of H3 Ser 10 (H3S10p) drives gene activation and chromosome condensation. To examine the relationship between H3S10p, H3K9me, and DNA methylation in Neurospora crassa, we built and tested mutants of the putative H3S10 phosphatase, PP1. A PP1-impaired mutant showed increased H3S10p and selective reduction of methylation of H3K9 and DNA. Similarly, amino acid substitutions of H3S10 abolished methylation of H3K9 and DNA. Thus, H3S10 dephosphorylation by PP1 is required for DNA methylation of some loci. 相似文献
5.
目的 应用DNA条形码技术对翻白草及易混品委陵菜进行分子鉴定,保障药材质量和临床用药安全。方法 提取翻白草及委陵菜的基因组DNA,扩增内转录间隔区2(ITS2)序列并双向测序,所得序列用SeqMan软件校对、拼接;在线双序列比对翻白草对照药材(FR)及委陵菜对照药材(WR)的ITS2序列,并预测其二级结构;从GenBank下载部分相关序列,运用MEGA X软件进行多序列比对,分析序列变异位点,计算种内、种间遗传距离,采用邻接法(NJ)构建系统进化树。结果 所有样品均成功扩增出ITS2序列,翻白草和委陵菜的ITS2序列长度均为210 bp。双序列比对结果表明,FR与WR的ITS2序列相似性为92.9%,二级结构存在明显差异。多序列分析结果表明,翻白草ITS2序列平均鸟嘌呤(G)+胞嘧啶(C)占比为63.0%,存在2个变异位点,种内遗传距离为0~0.009 6;委陵菜ITS2序列平均G+C占比为64.4%,存在5个变异位点,种内遗传距离为0~0.019 3;种间遗传距离为0.054 8~0.075 8。NJ树结果显示,翻白草、委陵菜聚为不同分支,可明显区分。结论 利用ITS2序列可以准确鉴别翻白草与委陵菜,为保障其安全用药提供了新的技术手段。 相似文献
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2012年,张家港市在个体口腔诊所中推行医院感染管理标准操作规程(SOP)行政指导工作,作者就张家港市个体口腔诊所推行医院感染管理标准操作规程(SOP)工作的做法和成效进行了初步探讨,并对个体口腔诊所医院感染管理标准操作规程(SOP)制订与现行卫生标准、规范如何衔接、医院感染管理监督执法的发展方向、卫生监督执法人员如何有效履职作出思考。 相似文献
9.
Michael Dörks Katharina Allers Falk Hoffmann 《Journal of the American Medical Directors Association》2019,20(3):287-293.e7
Objectives
In addition to routinely administered long-term medication, complex drug regimens of nursing home residents often include as needed or pro re nata (PRN) medication. However, there has been no systematic evaluation of the frequency and concomitants of PRN medication in nursing homes. The main objective of this systematic review was to provide a current assessment of PRN drug use in nursing homes.Design
A systematic literature search was performed. Data were identified from 4 electronic bibliographic databases: MEDLINE, Embase, CINAHL, and Scopus. Studies were included if they reported quantitative data on PRN drug use in nursing home residents.Results
Our search strategy resulted in 484 hits, of which 27 articles satisfied the inclusion criteria. The mean number of PRN drugs ranged between 0.4 and 4.9 per resident with a median of 2.5. The proportion of residents prescribed at least 1 PRN drug was between 48.4% and 97.4% (median = 74.9). Administration of prescribed PRN medication was rather low as the proportion of residents with administered PRN drugs ranged from 28% to 55%. Frequently prescribed PRN drugs were analgesics, laxatives, and sedatives. Advanced age, dementia, a higher number of regularly scheduled medications, and length of stay in the nursing home were associated with higher use of PRN drugs.Conclusions/Implications
Although not regularly administered, PRN drug use in nursing home residents should be taken into account as part of complex drug regimens. In that sense, there seems to be an inadequate number of studies reporting on it. When screening tools like the Beers Criteria are adapted, PRN drugs should be included. 相似文献10.