消旋酶法DL-丙氨酸的遗传毒性研究

目的 评价消旋酶法DL-丙氨酸的遗传毒性。方法 小鼠骨髓细胞微核实验设阴性对照组（纯水）、阳性对照组（环磷酰胺40 mg/kg）和消旋酶法DL-丙氨酸3个剂量组（10 000、5 000和2 500 mg/kg）,观察各组小鼠胸骨骨髓细胞微核发生率;小鼠精原细胞染色体畸变实验设阴性对照组（纯水）、阳性对照组（环磷酰胺40 mg/kg）和消旋酶法DL-丙氨酸3个剂量组（10 000、5 000和2 500 mg/kg）,观察各组小鼠睾丸精原细胞染色体畸变类型并计算畸变率。细菌回复突变实验（Ames实验）设空白对照组、溶剂对照组、阳性对照组和消旋酶法DL-丙氨酸5个剂量组（50、158、500、1 580、5 000 μg/皿和8、40、200、1 000、5 000 μg/皿）,计数各组回复突变菌落数。结果 小鼠骨髓细胞微核实验结果显示,各剂量组消旋酶法DL-丙氨酸微核细胞率与对照组的差异无统计学意义（P>0.05）;小鼠精原细胞染色体畸变实验结果显示,各剂量组消旋酶法DL-丙氨酸动物睾丸精原细胞染色体畸变率与对照组的差异无统计学意义（P>0.05）;细菌回复突变实验结果显示,在加或不加S9的情况下,各剂量组消旋酶法DL-丙氨酸对TA97a、TA98、TA100、TA102、TA1535菌株均无致突变作用,差异无统计学意义（P>0.05）。结论 消旋酶法DL-丙氨酸未见明显遗传毒性。     

哺乳动物细胞染色体畸变试验的标准化与背景数据采集

染色体畸变试验作为保健食品、化妆品、药品、医疗器械上市前常规开展的毒理学试验项目,是检测化学物质对染色体数量和结构影响的基本方法。确立标准化试验方法并积累一定的背景数据,是试验系统和数据真实可靠性的有力保障,可为科研人员和审评专家的数据分析提供有力依据。首先就影响染色体畸变试验结果的因素进行简要综述,继而通过回顾国内外2012-2017年期间发表的47篇有关哺乳动物细胞染色体畸变试验的研究来讨论如何规范化试验条件,并以国家药物安全评价监测中心2002-2017年汇总的背景数据为例阐释建立历史背景数据的要点。总之,严格参考OECD指导原则开展规范化的染色体畸变试验并通过长期积累建立一套对照受试物的背景数据是临床前遗传毒性研究的关键环节,有利于更好地对药物等受试物的潜在致染色体损伤作用进行合理而有效的判断。     

Pupillodynamics and corneal spherical aberrations in a set of Indian cataract patients and its implications for aberrometric customisation of intraocular lenses

Purpose:Assessment of pupil diameter in various light conditions and the corresponding corneal spherical aberrations in a cohort of Indian eyes with bilateral senile cataracts and the possible use of this data in aberrometric customization of intraocular lenses (IOLs).Methods:In this prospective observational study done at a tertiary eye care centre in India, the selected patients were subjected to measurement of their pupil diameters in scotopic, mesopic, and photopic conditions as well as the corresponding corneal spherical aberrations, using the Sirius Topographer (Costruzione Strumenti Oftalmici, Florence, Italy). Shapiro–Wilk test, Independent t-test, ANOVA with Bonferroni correction on post-hoc testing were used for statistical analysis.Results:104 eyes of 52 patients were enrolled for the study. The mean age was 53 ± 11.88 years. The mean scotopic, mesopic, and photopic pupil sizes were 4.37 mm (4.11–4.63 mm), 3.92 mm (3.71 mm–4.15 mm), and 3.37 mm (3.18–3.67 mm), respectively. There was a statistically significant difference (P = <0.001) in the mean corneal spherical aberration measured at the 6 mm zone (0.23 ± 0.02 microns) and at the 4 mm zone (0.06 ± 0.01 microns).Conclusion:The mean corneal spherical aberration corresponding to the average mesopic pupil size of our patient population was substantially lower than that of the scotopic pupil size and also less than the amount corrected by most of the negative aspheric IOLs. This perhaps indicates the need for customising IOLs based on the spherical aberrations of cornea at the zone corresponding to the mesopic pupil diameter for optimal residual total postoperative spherical aberrations.     

超声在诊断胎儿颜面畸形中的应用价值及颜面部畸形与染色体异常的关系研究

目的:探究超声在诊断胎儿颜面畸形中的临床价值,进一步分析颜面部畸形与染色体异常的关系。方法:回顾性分析2018年12月-2019年7月在笔者医院超声科行产前筛查的1533例孕妇的资料,以超声筛查胎儿颜面部异常者(超声异常组,n=30)和超声筛查胎儿颜面部正常但具有高危因素者(超声正常高危组,n=66)作为研究对象。记录超声及染色体检查结果,分析颜面部畸形与染色体异常的关系。结果:30例超声筛查颜面部异常胎儿中,8例单纯颜面部异常,22例颜面部异常合并其他异常。超声异常合并其他异常组NT厚度显著高于超声单纯异常组和超声正常高危组,差异有统计学意义(P<0.05)。超声异常组胎儿染色体异变率为20.00%,显著高于超声正常高危组的4.55%,差异有统计学意义(P<0.05)。结论:产前筛查中应用超声诊断可以明显提高染色体异常胎儿的检出率,值得临床推广应用。     

Optical mechanisms regulating emmetropisation and refractive errors: evidence from animal models

Our current understanding of emmetropisation and myopia development has evolved from decades of work in various animal models, including chicks, non-human primates, tree shrews, guinea pigs, and mice. Extensive research on optical, biochemical, and environmental mechanisms contributing to refractive error development in animal models has provided insights into eye growth in humans. Importantly, animal models have taught us that eye growth is locally controlled within the eye, and can be influenced by the visual environment. This review will focus on information gained from animal studies regarding the role of optical mechanisms in guiding eye growth, and how these investigations have inspired studies in humans. We will first discuss how researchers came to understand that emmetropisation is guided by visual feedback, and how this can be manipulated by form-deprivation and lens-induced defocus to induce refractive errors in animal models. We will then discuss various aspects of accommodation that have been implicated in refractive error development, including accommodative microfluctuations and accommodative lag. Next, the impact of higher order aberrations and peripheral defocus will be discussed. Lastly, recent evidence suggesting that the spectral and temporal properties of light influence eye growth, and how this might be leveraged to treat myopia in children, will be presented. Taken together, these findings from animal models have significantly advanced our knowledge about the optical mechanisms contributing to eye growth in humans, and will continue to contribute to the development of novel and effective treatment options for slowing myopia progression in children.     

In vitro investigation of the genotoxic and cytotoxic effects of thiacloprid in cultured human peripheral blood lymphocytes

Thiacloprid, a neonicotinoid insecticide, is widely used for controlling various species of pests on many crops. The potential genotoxic effects of thiacloprid on human peripheral blood lymphocytes (PBLs) were investigated in vitro by the chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and cytokinesis‐block micronucleus (MN) assays. The human PBLs were treated with 75, 150, and 300 μg/mL thiacloprid in the absence and presence of an exogenous metabolic activator (S9 mix). Thiacloprid increased the CAs and SCEs significantly at all concentrations (75, 150, and 300 μg/mL) both in the absence and presence of the S9 mix and induced a significant increase in MN and nucleoplasmic bridge formations at all concentrations for 24 h and at 75 and 150 μg/mL for 48‐h treatment periods in the absence of the S9 mix; and at all concentrations in the presence of the S9 mix when compared with the control and solvent control. Thiacloprid was also found to significantly induce nuclear bud (NBUD) formation at 300 μg/mL for 24 h and at 150 μg/mL for 48‐h treatment times in the absence of the S9 mix and at the two highest concentrations (150 and 300 μg/mL) in the presence of the S9 mix. Thiacloprid significantly decreased the mitotic index, proliferation index, and nuclear division index for all concentrations both in the absence and presence of the S9 mix. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 631–641, 2014.     

Pre-clinical in vitro and in vivo safety evaluation of bovine whey derived osteopontin,Lacprodan® OPN-10

Lacprodan® OPN-10 is a proprietary whey-based protein product that contains bovine-derived osteopontin (OPN), found in human milk and other bodily tissues. In vitro genotoxicity tests conducted according to accepted guidelines at up to 5000 μg/plate OPN failed to induce genetic mutations in Salmonella typhimurium strains and Escherichia coli strain and did not induce chromosomal aberrations or cytotoxicity in human lymphocytes. Administration of an acute dose of Lacprodan® OPN-10 (2300 mg/kg body weight) to male and female mice did not induce chromosomal damage or mitotic apparatus damage to erythroblasts from bone marrow. Lacprodan® OPN-10 was evaluated in a 13-week oral toxicity study in which rats were fed diets containing 0.5%, 1.0% and 2.0% Lacprodan® OPN-10. No test-article-related clinical observations or toxicological effects on body or organ weights, food consumption, ophthalmic effects, locomotor activity, hematology, clinical chemistry, urinalysis, or pathology were identified. In a teratogenicity study, administration of Lacprodan® OPN-10 up to 2500 mg/kg bw/day via gavage to pregnant rats had no effect on dams or pups. The No Observed Adverse Effect Level (NOAEL) for Lacprodan® OPN-10 in the 13-week toxicity study was 2.0% of the diet (equivalent to 1208 mg/kg bw/day in male rats and 1272 mg/kg bw/day in female rats).     

Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay,cytokinesis-block micronucleus test and chromosome aberrations test

Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells.Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay.Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ⩾1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated.Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans.     

智力低下儿的细胞微核检查分析

目的探讨染色体异常和细胞微核发生与智力低下的关系。方法选择40例行遗传咨询患儿作为智力低下组,20例正常儿童作为正常对照组,应用常规法分别制备智力低下儿和正常儿童的淋巴细胞及其染色体G显带的标本,检测2组核型和细胞微核率。结果 40例智力低下儿中,共检出15例染色体异常核型,检出率为37.5%,其中21-三体综合征10例（25.0%）;其微核发生率为12.5%,正常对照组染色体异常1例（5.0%）,微核率为3.26%。2组染色体异常发生率和微核率比较,差异有统计学意义（P〈0.01）。结论染色体畸变与微核的形成是引起智力低下发生的重要遗传学原因。     

Localization of cloned human DNA sequences and analysis of chromosomal alteration by in situ hybridization

Abstract: The in situ hybridization technique was used for the localization on human chromosomes of single-copy and repeated sequences and, in addition, for the characterization of altered human chromosomes. Two anonymous clones, single or low-copy, obtained from a human X chromosome library were localized on the distal part of the long arm and in the paracentromeric region of X chromosome, respectively. A genomic fragment of the single-copy thyroglobulin (TG) gene was used to confirm the localization on the distal part of the long arm of chromosome 8. The localization and distribution on human chromosomes of the glyceraldehyde-3-phosphate dehydrogenase (GAPD) multigene family obtained by in situ hybridization and by somatic cell hybrids were compared. A phosphoglycerate kinase (PGK) c-DNA clone, which detects genic and pseudogenic sequences on the X chromosome, was used for the characterization of three small ring markers present in unrelated female patients.