teratogenicity

致畸性
  • 文章类型: Journal Article
    大量氧化锌(ZnO-BPs)及其纳米颗粒(ZnO-NPs)经常用于各种人类产品中。Helisomaduryi胚胎可以作为研究NPs毒性的有效模型生物。这项研究旨在比较ZnO-BPs和ZnONPs在H.duryi胚胎阶段的致畸效力,以评估这种蜗牛作为ZnO-NPs在水生环境中的生物指示剂的实用性。通过测定LC50,研究两种ZnO形式的亚致死浓度对胚胎的影响,评估了致畸机制。研究它们的酶活性,氧化应激,和生化分析。进行SDS-PAGE电泳以评估ZnO-BP和ZnONP对蛋白质合成的影响。结果表明,H.duryi的veliger阶段是块状和纳米ZnO的特定阶段。ZnO-NP对蜗牛胚胎的毒性比ZnO-BPs更大。暴露于ZnO会影响开发中特定类型的缺陷,在BP的情况下,远远没有由NP引起的剧烈程度。因此,ZnO-NP在胚胎发育中的毒性是由于其独特的理化性质。观察到的畸形主要包括积水畸形,外植体,单眼症,贝壳畸形,和细胞裂解。几乎所有测试的氧化生物标志物都发生了显著变化,表明ZnONPs比ZnO-BPs表现出更多的氧化应激。此外,低浓度的ZnO会对veliger幼虫的有机物质产生许多干扰,例如总蛋白质和总脂质水平的降低和糖原水平的增加。结果表明,ZnO-BPs增加了蛋白质条带的数量。相反,ZnO-NPs从处理的卵团中隐藏了一条带,在对照组中发现。蜗牛胚胎是控制淡水蜗牛的合适模型。这项研究表明H.duryi胚胎可以作为研究ZnO-NP毒性的有效模型生物。
    Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails\' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.
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  • 文章类型: Journal Article
    以前检查抗抑郁药和先天性畸形的研究主要在西方国家进行,许多人受到重要的方法论限制。这项基于人群的研究确定了465,069名年龄在15-50岁之间的女性(包括1,705名在妊娠早期赎回≥1种抗抑郁药的处方),他们在2003年至2018年期间在香港以中国为主的人群中分娩了第一个和单胎孩子。使用全港公共医疗服务的医疗记录数据库,并采用倾向评分精细分层加权逻辑回归分析来评估妊娠早期暴露于抗抑郁药后任何重大和器官/系统特异性先天性畸形的风险。总体上严重畸形与任何抗抑郁药无关(加权比值比wOR,0.88[95CI,0.44-1.76]),特定的药物类别,或个体抗抑郁药。暴露于任何抗抑郁药均与心脏病风险增加相关(wOR,1.82[95CI,1.07-3.12])和呼吸异常(wOR,4.11[95CI,1.61-10.45])。暴露于选择性5-羟色胺再摄取抑制剂(SSRI)和多种AD类别与呼吸和心脏异常有关,分别。然而,这些确定的关联在敏感性分析中没有得到一致的确认,排除坚定的结论。观察到特定心脏缺陷与5-羟色胺-去甲肾上腺素再摄取抑制剂(SNRI)的关联,注意到三环抗抑郁药(TCA)和多个AD类别具有广泛的置信区间,暗示不精确的估计。总的来说,我们的研究结果表明,孕早期抗抑郁药物暴露与先天性畸形的风险增加并无明显相关性.需要进一步的研究来阐明个体抗抑郁药对特定畸形的相对安全性。
    Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44-1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07-3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61-10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.
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  • 文章类型: Journal Article
    大约1-2%的孕妇在怀孕期间在麻醉下接受非产科手术。这篇综述专门针对在资源有限的环境中接受非产科手术的孕妇的麻醉管理。
    在划分主要问题之后,范围,和纳入标准,跨电子来源实施了利用先进技术的全面搜索策略,数据库,和网站来识别相关文章。在文献评估过程中采用了严格的筛选过程。2020年系统审查和荟萃分析(PRISMA)的首选报告项目声明指导了本次审查的进行,确保遵守标准化的报告实践。
    最初从数据库和网站确定了总共240篇文章。筛选标题和摘要后,85篇论文被排除在外,另有43人因重复被删除。随后,对68个项目进行资格筛选。最后,回顾了30篇专门针对非产科手术孕妇的麻醉考虑因素的论文。
    全面的术前评估对所有患者都至关重要,特别注意修改麻醉管理以适应怀孕期间的生理变化。紧急和紧急手术应在怀孕期间迅速进行,以优化母亲和胎儿的结局。维持子宫胎盘灌注通常涉及避免母体低氧血症,低血压,高碳酸血症和低碳酸血症,极端温度,和压力。当被认为安全时,区域麻醉可能对母亲和胎儿都有良好的结局.
    UNASSIGNED: Approximately 1-2% of pregnant women undergo non-obstetric surgery under anaesthesia during their pregnancy. This review specifically targets anaesthesia management for pregnant women undergoing non-obstetric surgery in resource-limited settings.
    UNASSIGNED: Following the delineation of primary questions, scope, and inclusion criteria, a comprehensive search strategy utilizing advanced techniques was implemented across electronic sources, databases, and websites to identify relevant articles. A rigorous screening process was applied during the literature evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guided the conduct of this review, ensuring adherence to standardized reporting practices.
    UNASSIGNED: A total of 240 articles were initially identified from databases and websites. After screening titles and abstracts, 85 papers were excluded, and an additional 43 were removed due to duplication. Subsequently, 68 items were subjected to eligibility screening. Finally, 30 papers that specifically addressed anaesthetic considerations for pregnant women undergoing non-obstetric operations were reviewed.
    UNASSIGNED: Thorough preoperative evaluation is essential for all patients, with particular attention to modifications in anaesthetic management to accommodate physiological changes during pregnancy. Urgent and emergent surgeries should proceed promptly during pregnancy to optimize outcomes for both the mother and foetus. Maintaining uteroplacental perfusion generally involves avoiding maternal hypoxaemia, hypotension, hyper- and hypocapnia, temperature extremes, and stress. When deemed safe, regional anaesthesia may offer favourable outcomes for both the mother and foetus.
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  • 文章类型: Journal Article
    根据欧盟委员会的两项要求,EFSA营养小组,要求新型食品和食品过敏原(NDA)就预制维生素A和β-胡萝卜素的可耐受上限摄入量(UL)的修订发表科学意见。对文献进行了系统评价,以确定摄入过量维生素A对健康的优先不利影响。即致畸性,与骨骼健康相关的肝毒性和终点。现有数据无法解决β-胡萝卜素是否可以增强预先形成的维生素A毒性。选择致畸作用作为预制维生素A的UL的基础的关键影响。小组建议对成年人保留3000μgRE/天的预制维生素A的UL。本UL适用于男性和女性,包括育龄妇女,孕妇和哺乳期妇女以及绝经后妇女。使用异速测量(体重0.75)将该值缩小到其他人群,导致UL介于600μgRE/天(4-11个月的婴儿)和2600μgRE/天(15-17岁的青少年)之间。根据现有的摄入量数据,如果食用肝脏,欧洲人群不太可能超过预制维生素A的UL,内脏及其产品限于每月一次或更少。建议计划怀孕或怀孕的妇女不要食用肝脏产品。选择肺癌风险作为过量补充β-胡萝卜素的关键影响。现有数据不足以描述剂量反应关系和确定参考点;因此,没有UL可以建立。没有迹象表明从背景饮食中摄取β-胡萝卜素与不利的健康影响相关。吸烟者应避免食用含有β-胡萝卜素的食品补充剂。一般人群补充β-胡萝卜素的使用应限于满足维生素A需求的目的。
    Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 μg RE/day (infants 4-11 months) and 2600 μg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β-carotene. The use of supplemental β-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.
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  • 文章类型: Journal Article
    植物生长调节剂(PGRs)越来越多地用于促进可持续农业,但是它们不受管制的使用引起了人们对潜在环境风险的担忧。吲哚-3-乙酸(IAA),一种常用的PGR,其在体内斑马鱼模型中的发育毒性一直是研究的主题。IAA暴露于斑马鱼胚胎引起的氧化应激,脂质过氧化,和细胞凋亡。该研究还揭示了关键的抗氧化基因,包括sod,猫,和bcl2下调,而bax和p53等促凋亡基因上调。IAA暴露还通过下调myl7,amhc,和vmhc基因,并可能影响斑马鱼的神经行为。通过IAA暴露的斑马鱼组织的HPLC分析证实了IAA的积累。这些发现强调了需要进一步研究IAA使用的潜在生态后果以及可持续农业实践的必要性。
    Plant growth regulators (PGRs) are increasingly used to promote sustainable agriculture, but their unregulated use raises concerns about potential environmental risks. Indole-3-acetic acid (IAA), a commonly used PGR, has been the subject of research on its developmental toxicity in the in-vivo zebrafish model. IAA exposure to zebrafish embryos caused oxidative stress, lipid peroxidation, and cellular apoptosis. The study also revealed that critical antioxidant genes including sod, cat, and bcl2 were downregulated, while pro-apoptotic genes such as bax and p53 were upregulated. IAA exposure also hampered normal cardiogenesis by downregulating myl7, amhc, and vmhc genes and potentially influencing zebrafish neurobehavior. The accumulation of IAA was confirmed by HPLC analysis of IAA-exposed zebrafish tissues. These findings underscore the need for further study on the potential ecological consequences of IAA use and the need for sustainable agricultural practices.
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  • 文章类型: Journal Article
    近年来,药物在水生环境中的存在得到了极大的关注。卡马西平,一种常用的抗癫痫药,在水生环境中一直发现浓度从纳克到微克不等,引起人们对其对水生生物的潜在负面影响的担忧。该研究检查了环境相关浓度和亚致死浓度的卡马西平在蚊子中的急性和慢性神经毒性作用。经过96小时的暴露期,卡马西平对G.affinis的中位致死浓度(LC50)为24mgL-1。对于目前的研究,亚致死浓度,即选择LC50值的十分之一(2.4mgL-1)和五分之一(4.8mgL-1)用于评估神经毒性作用以及环境相关浓度(13ngL-1).研究结果表明,卡马西平对鱼类的典型生长和行为具有破坏性影响。在急性暴露阶段,在鱼中观察到身体畸形,导致新生儿和新生儿后死亡。此外,卡马西平的神经毒性作用通过各种神经参数的改变得到了清楚的证明,包括乙酰胆碱酯酶,多巴胺,γ-氨基丁酸,血清素,单胺氧化酶,5-羟基吲哚乙酸,肾上腺素,和肾上腺素。这些发现引起了人们对鱼类种群在自然环境中生存的担忧。
    In recent years, the presence of pharmaceuticals in the aquatic environment has gained a significant attention. Carbamazepine, a commonly prescribed antiepileptic drug, has been consistently found in aquatic environments at concentrations ranging from nanograms to micrograms, raising concerns about its potential negative impacts on aquatic organisms. The study examined the acute and chronic neurotoxic effects of environmentally relevant and sublethal concentrations of carbamazepine in the mosquitofish Gambusia affinis. After a 96-hour exposure period, the median lethal concentration (LC50) of carbamazepine for G. affinis was determined as 24 mg L - 1. For the current study, sublethal concentrations i.e., one-tenth (2.4 mg L - 1) and one-fifth (4.8 mg L - 1) of the LC50 value were chosen for assessing the neurotoxic effects along with the environmentally relevant concentration (13 ng L - 1). The research findings indicated that carbamazepine had a disruptive impact on the typical growth and behavior of the fish. During the acute exposure phase, physical deformities were observed in the fish, resulting in neonatal and postneonatal fatalities. Furthermore, the neurotoxic effects of carbamazepine were clearly demonstrated through alterations in various neurological parameters, including acetylcholinesterase, dopamine, gamma-aminobutyric acid, serotonin, monoamine oxidase, 5-hydroxyindole acetic acid, adrenaline, and nor-adrenaline. These findings raise concerns about the survival of fish populations in their natural environment.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    对于怀孕时需要继续服用抗精神病药物的患者,存在很多争论,因为必须权衡与抗精神病药物本身相关的潜在致畸和畸形作用。为了解决这个问题,我们对PubMed进行了系统的审查,使用以下策略的PsycINFO和CINHAL数据库和ClinicalTrials.gov注册:(毒性或致畸性或畸形*或“出生缺陷*”或“先天性异常”或“先天性异常”或“大脑异常”或“行为异常”或“行为异常”)和抗精神病药物*(妊娠或妊娠或哺乳期或产前或产后)2023年9月27日。我们发现38项研究符合资格。最古老的文章发表于1976年,而大多数文章都是最近发表的。大多数研究得出结论,抗精神病药,尤其是第二代抗精神病药,缺乏致畸潜力,虽然很少有研究没有定论并推荐复制。大多数权威文章来自波士顿地区,在那里实施了大型数据库来研究精神药物的畸形潜力。其他可靠的数据库来自北欧登记册。总体结论是,抗精神病药物与畸形的关系并不比疾病本身更多;大多数研究认为,没有理由在怀孕期间停用抗精神病药物。
    There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR \"birth defect*\" OR \"congenital abnormality\" OR \"congenital abnormalities\" OR \"brain changes\" OR \"behavioral abnormalities\" OR \"behavioral abnormalities\") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.
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  • 文章类型: Journal Article
    阿斯巴甜,一种广泛使用的人造甜味剂,存在于全球许多食品和饮料中。它与潜在的神经毒性和发育缺陷有关。然而,其对胚胎发育的致畸作用及其潜在机制有待阐明。我们研究了阿斯巴甜对斑马鱼发育和致畸性的浓度和时间依赖性影响。我们专注于沉默调节蛋白1(SIRT1)和叉头盒转录因子(FOXO)的作用,在神经发育中起关键作用的两种蛋白质。发现阿斯巴甜暴露减少斑马鱼幼虫的形成和软骨的发育。它还通过改变斑马鱼的头部长度和运动行为来延迟受精后的发育。基于RNA测序的DEG分析显示SIRT1和FOXO3a参与神经发育。计算机模拟和体外分析表明,阿斯巴甜可以靶向并减少神经元细胞中SIRT1和FOXO3a蛋白的表达。此外,阿斯巴甜通过抑制SIRT1在神经元细胞中的核转位来触发自噬通量的减少。研究结果表明,阿斯巴甜可导致斑马鱼胚胎发育缺陷和致畸性,并通过损害神经元细胞的SIRT1/FOXO3a轴减少自噬。
    Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells.
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  • 文章类型: Case Reports
    TreacherCollins综合征(TCS)是一种罕见的先天性颅面发育障碍,其特征是许多发育异常仅限于头颈部。大多数TCS病例以常染色体显性遗传方式遗传。TCS的诊断依赖于临床和影像学检查结果。参与TCS的四个基因是TCOF1、POLR1D、POLR1C,POLR1B
    在本报告中,我们介绍了一个7岁的摩洛哥男孩,他表现出独特的畸形特征,包括结肠瘤和颧骨发育不全。通过基因分析,在TCOF1基因中发现了一个突变,最终证实了叛逆者柯林斯综合症的存在.值得的是,由于最初的误解,即观察到的畸形综合征是药物致畸的结果,因此正确的病因诊断被大大延迟。
    此案例强调了如果用药后出现任何不良事件,寻求药物警戒建议的重要性。此外,要求进行遗传咨询以确定任何畸形综合征的病因诊断可以显着减少患者及其家人可能承受的长期社会和心理痛苦。
    UNASSIGNED: Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development characterized by numerous developmental anomalies that are restricted to the head and neck. Most TCS cases are inherited in an autosomal dominant manner. The diagnosis of TCS relies on clinical and radiographic findings. The four genes involved in TCS are TCOF1, POLR1D, POLR1C, and POLR1B.
    UNASSIGNED: In this report, we present the case of a 7-year-old Moroccan boy who exhibited distinctive dysmorphic features, including coloboma and zygomatic bone hypoplasia. Upon genetic analysis, a mutation in the TCOF1 gene was identified, conclusively confirming the presence of Treacher Collins Syndrome. It is worthy that the correct etiological diagnosis was significantly delayed due to the initial misperception that the observed malformation syndrome was a result of drug teratogenicity.
    UNASSIGNED: This case highlights the importance of seeking pharmacovigilance advice if any adverse event occurs following medication use. Furthermore, requesting a genetic consultation to establish a confirmed etiological diagnosis for any malformation syndrome can significantly reduce the protracted social and psychological suffering that patients and their families may endure.
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