Genotoxicity assessment of three reference chemicals in rat hepatocytes by alkaline comet assay / 上海预防医学

Objective:To establish a comet test method for detection of genotoxicity of three reference chemicals in rat liver cells. Methods:6-10 week old Sprague Dawley rats were randomly divided into 4 groups， with normal saline （0.9% NaCl solution） as negative control group. Animals in three test groups were treated， respectively， with ethyl methanesulfonate （EMS） 200 mg/kg， N-methyl-N-nitrosourea （MNU） 50 mg/kg， and D-mannitol 2 000 mg/kg. There were 10 animals in each group， 5 males and 5 females. The animals received two times （21 h interval） of test compounds through intragastric administration， and their clinical symptoms and body weight changes were recorded during the experiment. The rats were sacrificed 3 h after the last exposure. The liver was weighed， then used to prepare single-cell suspensions for the alkaline comet test which determines the average tail DNA content percentage （DNA%） of hepatocytes and other comet indicators. Results:（1） D-mannitol， EMS and MNU did not show significant toxicity in the whole animal. （2） The mean values of tail DNA content percentage （DNA%） of rat hepatocytes in EMS ［（60.07±24.69）%］ and MNU ［（41.66±22.35）%］ groups were higher than that in the negative control group ［（2.32±1.39）%］ and the difference was statistically significant （P<0.05）. The difference between D-mannitol group ［（3.06±3.30）%］ and the negative control group was not significant （P>0.05）. Conclusion:This laboratory has established a comet test method using hepatocytes from treated rats. Among three testing chemicals， EMS and MNU have displayed genotoxicity by this assay， but no genotoxicity was observed in D-mannitol treated animals.

Hormetic Effects of Yttrium on Male Sprague-Dawley Rats / 生物医学与环境科学（英文）

To evaluate hormesis induced by Yttrium (Y) nitrate in male rats, Y was offered to F0 mother rats and F1 offspring at concentrations of 0, 20, 80, and 320 ppm daily from gestational day (GD) 0 through postnatal day 70 (PND 70). The F1 offspring were evaluated with respect to motor function, learning and memory, and histopathology. Administration of Y improved motor function in a dose dependent manner. In the 20 ppm group, body weight and spatial learning and memory were increased, while the latter was decreased in the 320 ppm group. Additionally, in the 20 ppm and 80 ppm, but not the 320 ppm groups, Y reduced the anogenital distance, which indicated an anti-androgen effect. These results suggest that Y follows a hormetic concentration-related trend with an inverted U-shape.

Requirements analysis on defibrillation protection testing and marking of multi-parameter monitor / 医疗卫生装备

Objective To study the requirements for defibrillation protection testing and marking of the multi-parameter monitor to facilitate the manufacturer to understand related standards and design products rationally.Methods The background and principle were described for defibrillation protection testing of the monitor.The requirements of related standards were analyzed for defibrillation protection testing and marking,and the defibrillation protection flow was explored during the clinical application of the monitor.Results The multi-parameter monitor might be damaged in case of the monitor's deficiencies in the the defibrillation protection,even patient's failure in the defibrillation protection or death might occur,and the electrical shock could be caused also to medical staffs.Conclusion The defibrillation protection is of great significance for the multi-parameter monitor,and considerations have to be posed on standards requirements and the monitor's clinical application so as to decrease its use risks.

Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the health effects of parental dietary exposure to GM rice TT51 on the male reproductive system of rat off spring.</p><p><b>METHODS</b>Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents' for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular (HPT) axis.</p><p><b>RESULTS</b>No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis.</p><p><b>CONCLUSION</b>The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.</p>

Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl phthalate (DBP) in male Sprague Dawley (SD) rats.</p><p><b>METHODS</b>Forty 4-week-old male rats weighing 115-125 g were randomly divided into BPA-treated, DBP-treated group, BPA+DBP-treated and control groups and fed with a soy- and alfalfa-free diet containing 285.4 ppm BPA, 285.4 ppm DBP, 285.4 ppm BPA plus 285.4 ppm DBP, and a control diet, respectively, for 90 consecutive days. At the end of the study, the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed. Organs, including liver, kidneys, spleen, thymus, heart, brain, and testis underwent pathological examination. The androgen receptor (AR), gonadotropin-releasing hormone receptor (GNRHR), and progesterone hormone receptor (PR) genes from the hypothalamus were detected by real-time PCR. The biomedical parameters were analyzed.</p><p><b>RESULTS</b>No significant difference was found in food intake, body weight, tissue weight, organ/brain weight ratio, and biomedical parameters among the four groups (P>0.05). However, BPA and DBP up-regulated AR, PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA+DBP group.</p><p><b>CONCLUSION</b>The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.</p>

Estrogen receptor α and β expressions in hypothalamus-pituitary-ovary axis in rats exposed lactationally to soy isoflavones and bisphenol A / 生物医学与环境科学（英文）

<p><b>OBJECTIVES</b>This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones (SIF) and bisphenol A (BPA) and to examine estrogen receptor α (ERα) and estrogen receptor β (ERβ) expressions in hypothalamus-pituitary-ovary axis and uterus.</p><p><b>METHODS</b>Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil (control), 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 (PND5-11) by gavage. On PND12 and PND70, 10 female litters were killed and hypothalamus, pituitary, ovary and uterus were collected. ERα and ERβ expressions in these organs were detected with Western blotting assay. And vaginal opening time and estrus cycle were examined in animals fed for PND70.</p><p><b>RESULTS</b>On PND12, the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats (P<0.05). But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA. On PND 70, however, the relative uterine weight in each treatment group was not statistically different from that in the control group (P>0.05). Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group (P>0.05). Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus, pituitary, ovary and uterus on PND12 and PND70. These regulation patterns for ERα and ERβ were different in different organs at different time points.</p><p><b>CONCLUSION</b>Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats, which disappeared in later life. But these data fail to suggest a possibility for synergic actions between SIF and BPA. It was also demonstrated that the uterotrophic effects of SIF and BPA exposure might, at least, involve modification of ERα or ERβ expressions in the hypothalamus-pituitary-ovary axis.</p>

Analysis of 51 cases of medical disputes in death after percutaneous coronary intervention / 法医学杂志

OBJECTIVE@#To investigate the causes and features of medical disputes in percutaneous coronary intervention (PCI) in the cardiology and to provide references for forensic expert testimony and medical disputes prevention.@*METHODS@#Fifty one disputed fatal cases in PCI were analyzed in terms of the cause of death, informed consent and medical operations retrospectively.@*RESULTS@#Thirty five cases were due to medical negligence, 28 due to defect technical operation, 2 due to mistake medical management and 5 due to both defect technical operation and mistake medical management.@*CONCLUSION@#The causes of PCI medical negligence are defect medical operation, violate medical disciplines and insufficiency of informed consent.

Subchronic toxicity study on soy isoflavones in rats / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the subchronic toxicity of soy isoflavones (SIF) in male rats.</p><p><b>METHOD</b>Fifty Sprague-Dawley rats were randomly divided into 5 groups, 10 rats per group. SIF were given to rats in different groups by gavage at dose of 0, 0.2, 0.5, 1.5, and 4.5 g/kg bw, respectively for 13 weeks. Clinical manifestations, body weight, and food consumption were observed weekly. At the end of the study, urinalysis, hematology, clinical chemistry, total testosterone, and follicle-stimulating hormone were tested, and histopathological examinations were performed.</p><p><b>RESULTS</b>No mortality, ophthalmic abnormalities or treatment-related clinical signs were identified during the study. As compared with the control group, significantly lower body weights and food consumption were observed in 1.5 and 4.5 g/kg bw groups. In clinical chemistry tests, triglyceride was significantly decreased and high-density lipoprotein cholesterol was significantly increased in all SIF-treated groups. Total testosterone levels were significantly lower in 0.50, 1.50, and 4.5 g/kg bw dose groups than in the control group. Microscopic examination showed that the mammary glands exhibited hyperplasia and excreted latex in rats of the 4.5 g/kg bw group. No changes attributable to treatment of SIF in other parameters were found.</p><p><b>CONCLUSION</b>SIF at high dosages caused significant endocrine disruption in male rats. The no observed adverse effect level (NOAEL) of SIF to male rats in this study is considered to be 0.20 g/kg bw.</p>

Remote postconditioning by brief renal ischemia and reperfusion reduces acute myocardial ischemia and reperfusion induced myocardial apoptosis in rabbits / 中华心血管病杂志

<p><b>OBJECTIVES</b>To observe the effects of renal ischemic postconditioning (RI-Post) on myocardial apoptosis in rabbits with acute myocardial ischemia and reperfusion.</p><p><b>METHODS</b>All rabbits were subjected to 60 minutes ischemia by left anterior descending coronary artery occlusion (LADO) and 6 hours reperfusion. The rabbits are randomly divided into 3 groups (n = 8 in each group): (1) Ischemia-reperfusion (IR): LADO and reperfusion without additional intervention; (2) RI-Post: after 60 minutes of LADO, the left renal artery was occluded for 30 seconds and reperfused for 30 seconds and repeated 3 times, then the coronary artery was reperfused for 6 hours; (3) Medication intervention (MI): 10 minutes before coronary reperfusion, rabbits were treated with PKC antagonist GF109203X (0.05 mg/kg, IV), followed by RI-Post treatment and 6 hours coronary reperfusion. Myocardial apoptosis was measured by TUNEL and the myocardial Bcl-2 and Bax protein expressions were assessed by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the IR group and the MI group, myocardial apoptosis was significantly reduced (P < 0.05) and the Bcl-2 protein expression increased (P < 0.01) while the Bax protein expression decreased (P < 0.05) in the RI-Post group.</p><p><b>CONCLUSIONS</b>Remote renal postconditioning applied right before the onset of coronary artery reperfusion can reduce the myocardial apoptosis induced by myocardial ischemia and reperfusion and up-regulate Bcl-2 while down-regulate Bax expression possibly by activation of protein kinase C.</p>

Genetic damage in peripheral blood lymphocyte of coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).</p><p><b>METHODS</b>One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire.</p><p><b>RESULTS</b>Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P < 0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P < 0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work.</p><p><b>CONCLUSION</b>Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.</p>

A study on the inherited susceptibility of chromosomal damage in peripheral blood lymphocytes among coke oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.</p><p><b>METHODS</b>One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction.</p><p><b>RESULTS</b>In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk.</p><p><b>CONCLUSION</b>Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.</p>

Relationship of polycyclic aromatic hydrocarbon exposure with peripheral blood lymphocyte DNA damage in coke oven workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers.</p><p><b>METHODS</b>Two hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire.</p><p><b>RESULTS</b>The lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P < 0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P < 0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage.</p><p><b>CONCLUSION</b>There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.</p>

A study on the relationship between urinary 1-hydroxypyrene level and early genetic effect among coke oven workers / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the urinary 1-hydroxypyrene level and cytokinesis-block micronucleus and the olive moment of comet assay in peripheral blood lymphocyte in coke oven workers.</p><p><b>METHODS</b>One hundred and thirty-three workers from a coke plant and 28 referents without occupational PAH exposure were recruited in this study. Urinary level of 1-hydroxypyrene was measured by alkaline hydrolysis combined with high performance liquid chromatography as an internal exposure dose, and the DNA and chromosomal damage of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis-block micronucleus method. Personal information including occupational history, age, sex, smoking and alcohol drinking, was collected by questionnaire.</p><p><b>RESULTS</b>There existed a good correlationship between the urinary level of 1-hydroxypyrene and frequency of micronuclei per 1 000 binucleated cells or the olive moment of comet assay in the study subjects, after adjusting for sex, age, smoking and alcohol drinking (r > 0.25, P < 0.01). One hundred and sixty-one subjects were divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30 - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol drinking by multiple nonparametric analysis of covariance, the median of olive moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67, significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively, significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00 per thousand ).</p><p><b>CONCLUSIONS</b>The comet assay of peripheral blood lymphocyte was more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis-block micronucleus.</p>