Analysis of individual and combined estrogenic effects of bisphenol, nonylphenol and diethylstilbestrol in immature rats with mathematical models

BACKGROUND@#Traditional toxicological studies focus on individual compounds. However, this single-compound approach neglects the fact that the mixture exposed to human may act additively or synergistically to induce greater toxicity than the single compounds exposure due to their similarities in the mode of action and targets. Mixture effects can occur even when all mixture components are present at levels that individually do not produce observable effects. So the individual chemical effect thresholds do not necessarily protect against combination effects, an understanding of the rules governing the interactive effects in mixtures is needed. The aim of the study was to test and analyze the individual and combined estrogenic effects of a mixture of three endocrine disrupting chemicals (EDCs), bisphenol A (BPA), nonylphenol (NP) and diethylstilbestrol (DES) in immature rats with mathematical models.@*METHOD@#In the present study, the data of individual estrogenic effects of BPA, NP and DES were obtained in uterotrophic bioassay respectively, the reference points for BPA, NP and DES were derived from the dose-response ralationship by using the traditional no observed adverse effect (NOAEL) or lowest observed adverse effect level (LOAEL) methods, and the benchmark dose (BMD) method. Then LOAEL values and the benchmark dose lower confidence limit (BMDL) of single EDCs as the dose design basis for the study of the combined action pattern. Mixed prediction models, the 3 × 2 factorial design model and the concentration addition (CA) model, were employed to analyze the combined estrogenic effect of the three EDCs.@*RESULTS@#From the dose-response relationship of estrogenic effects of BPA, NP and DES in the model of the prepuberty rats, the BMDL(NOAEL) of the estrogenic effects of BPA, NP and DES were 90(120) mg/kg body weight, 6 mg/kg body weight and 0.10(0.25) μg/kg body weight, and the LOAEL of the the estrogenic effects of three EDCs were 240 mg/kg body weight, 15 mg/kg body weight and 0.50 μg/kg body weight, respectively. At BMDL doses based on the CA concept and the factorial analysis, the mode of combined effects of the three EDCs were dose addition. Mixtures in LOAEL doses, NP and DES combined effects on rat uterine/body weight ratio indicates antagonistic based on the CA concept but additive based on the factorial analysis. Combined effects of other mixtures are all additive by using the two models.@*CONCLUSION@#Our results showed that CA model provide more accurate results than the factorial analysis, the mode of combined effects of the three EDCs were dose addition, except mixtures in LOAEL doses, NP and DES combined effects indicates antagonistic effects based on the CA model but additive based on the factorial analysis. In particular, BPA and NP produced combination effects that are larger than the effect of each mixture component applied separately at BMDL doses, which show that additivity is important in the assessment of chemicals with estrogenic effects. The use of BMDL as point of departure in risk assessment may lead to underestimation of risk, and a more balanced approach should be considered in risk assessment.

Estimated assessment of cumulative dietary exposure to organophosphorus residues from tea infusion in China

BACKGROUND@#China has the world's largest tea plantation area in the world. To sustain high yields of the tea, multiple pesticides are used on tea crops to control pests. Organophosphorus (OP) pesticides are among the most widely used types of agricultural pesticides in China. As tea is a significant potential source of exposure to pesticide residues, the public concern has increased in relation to pesticide residues found in tea in China. The aim of the study was to estimate cumulative dietary exposure to OP residues from tea infusion for Chinese tea consumers to determine whether exposure to OP residues from tea infusion is a cause of health concern for tea consumers in China.@*METHODS@#OP residue data were obtained from the China National Monitoring Program on Food Safety (2013-2014), encompassing 1687 tea samples from 12 provinces. Tea consumption data were obtained from the China National Nutrient and Health Survey (2002), comprising 506 tea consumers aged 15-82 years. The transfer rates of residues from tea leaves into tea infusions were obtained from the literature. The relative potency factor (RPF) approach was used to estimate acute cumulative exposure to 20 OP residues from tea infusion using methamidophos as the index compound. Dietary exposure was calculated in a probabilistic way.@*RESULTS@#For tea consumers, the mean and the 99.9th percentile (P99.9) of cumulative dietary exposure to OP residues from tea infusion equalled 0.08 and 1.08 μg/kg bw/d. When compared with the acute reference dose (ARfD), 10 μg/kg bw/d for methamidophos, this accounts for 0.8 and 10.8% of the ARfD.@*CONCLUSIONS@#Even when considering OP residues from vegetables, fruits and other foods, there are no health concerns based on acute dietary exposure to OP residues from tea infusion. However, it is necessary to strengthen the management of the OP pesticides used on tea in China to reduce the risk of chronic dietary exposure to OPs from tea infusion.

Liquid milk exposure and risk assessment of thiocyanate in Chinese populations / 中华预防医学杂志

Objective@#To analyze liquid milk exposure of thiocyanate among Chinese population and preliminarily assess its health risk.@*Methods@#A total of 2 059 raw milk samples were collected during 2013 and 2014 from 12 Chinese provinces, New Zealand and Netherlands. Farms were chosed according to the main sources of dairy companies, the distribution of farms and the yield of milk. Content of thiocyanate were detected by ion chromatography. Liquid milk consumption data were taken from Chinese beverage and alcoholic beverage consumption survey in 18 cities or counties in 9 provinces, including 16 775 subjects older than 3. A simple distribution model was used to estimate the exposure of thiocyanate from liquid milk. The tolerable daily intake (TDI) of thiocyanate was made 0.08 mg·kg-1·d-1. Then the exposures of different age groups were compared with TDI.@*Results@#Finally, 1 331 samples out of 2 059 were detected to contain thiocyanate. The detection rate was 65%. The average concentration of thiocyanate was 2.11 mg/kg, with a range of 0.10-16.20 mg/kg. The general population's consumption of thiocyanate by drinking liquid milk was 0.001 mg · kg-1 · d-1, which was lower than TDI. The P95 of general population and consumers were 0.009 mg · kg-1 · d-1 and 0.020 mg·kg -1·d-1 respectively, which were also lower than TDI. Mean exposures of population aged 3-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 0.007, 0.003, 0.002, 0.001 and 0.001 mg · kg-1·d-1 respectively, which were all lower than TDI.@*Conclusion@#The results suggested that the health risk of thiocyanate exposure by drinking liquid milk among Chinese population was at a low level. However, milk products for children deserve more concern.

Construction and prospection of percutaneous coronary intervention quality control system / 天津医药

In 21th century, percutaneous coronary intervention (PCI) technique enters in rapid development stage in China. From 2009, quality control system of PCI runs in national scale. Since then, the national quality control center estab?lished cooperative relationship with the provincial quality control centers. Official website and quality control tools were im?proved. PCI data were collected and analyzed annually, and then reported to the regulatory body and published to the public. Audit was run irregularly. Quality control centers were also involved in some other related affairs such as training course and admission. The quality control system lead PCI in China to an improved daily practice and control PCI application all overthe country in terms of data. In the future, the quality control techniques and teamwork will be further improved. And quality evaluation system and management team will be perfected gradually. Quality control will be extended from PCI to coronary heart disease and combined with audit of coronary heart disease. According to the quality control data, the quality and its rank of medical centers will be published in certain range. So that we can provide better care to the coronary heart disease pa?tients.

Dietary intake and risk assessment of diethylhexyl phthalate in Chinese populations / 中华预防医学杂志

<p><b>OBJECTIVE</b>To assess dietary exposure of diethylhexyl phthalate(DEHP) among Chinese population, including general population, children aged 2-6 years, adolescent aged 7-12, young people aged 13-17, adults aged 18-59 years old as well as older people aged 60 and above and its health risk.</p><p><b>METHODS</b>A total of 6 650 food samples were collected during 2011 to 2013 from 140 local markets of 14 provinces in China, which covered major foods in China. Samples were detected by GC-MS and categorized into 22 food groups. Food consumption data were taken from China National Nutrition and Health Survey performed in 2002 including 68 959 subjects. Mean concentrations of DEHP in food were combined with individual food consumption data to estimate dietary exposure, and food contributors to dietary DEHP intake were also calculated. Then, the exposure was compared with the tolerable daily intake (TDI, 50 µg·kg(-1)-d(-1)) of DEHP.</p><p><b>RESULTS</b>DEHP level in foods (n = 6 650) was in the range of not detected to 43.80 mg/kg. Mean dietary intakes of DEHP in general population was 2.07 (95% CI: 0.06-4.09) µg·kg(-1)·d(-1), accounting for 4.14 percent of TDI (50 µg·kg(-1)·d(-1)). Mean dietary intake for population aged 2-6, 7-12, 13-17, 18-59 as well as elderly aged 60 and above were 3.92 (95% CI: 0.83-7.01), 3.02 (95% CI: 0.69-5.36), 2.17 (95% CI: 0.54-3.81), 1.83 (95% CI: 0.46-3.21) and 1.66 (95% CI: 0.38-2.94) µg·kg(-1)·d(-1) respectively. The 97.5 percentile intakes in the general populations was 4.73 µg·kg(-1)·d(-1), accounting for 9.46% of TDI. Main food sources of DEHP were rice (28.4% (0.59/2.07)), melon solanaceous vegetables (14.7% (0.30/2.07)) and flour (13.2% (0.27/2.07)) for the general population.</p><p><b>CONCLUSION</b>The results suggested that dietary exposure to DEHP among Chinese population was lower than tolerable daily intake of DEHP and there were no health concerns based on generally accepted exposure limits. Rice, melon solanaceous vegetables and flour were main food contributors of DEHP dietary intake for Chinese populations.</p>

Assessment of trans-fatty acids intake via bakery food among above three-year-old population in Beijing and Guangzhou city / 中国药理学与毒理学杂志

OBJECTIVE To investigate trans-fatty acids (TFA)contents in bakery food and assess TFA intake via bakery food and its energy contribution in Beijing and Guangzhou city.METHODS Bak-ery food sa mples were collected in 201 1 ,standard GC-method were used to determine TFA content,da-ta of TFA content were analyzed by t-test to evaluate for statistically significant differences.Si mple distri-bution model(determinative risk assess ment)of TFA intake was used to calculate individual TFA intake per day(g·d -1 ,% of total energy)in different populations(grouped by ages).RESULTS Average TFA content was ranging fro m 0.01 to 0.83 g /100 g sa mple in various kinds of bakery food.TFA con-tents were equal to or lower than 0.3 g /100 g in 77.1 % of biscuits,71 .8% of bread,67.0% of pas-tries.Wafer biscuit,sandwich biscuit,puff,cake,and croissants had higher TFA contents than others, and the level was 0.65 -0.83 g /100 g sa mple.TFA content in sandwich biscuit and pie decreased sig-nificantly after 2007.Average TFA intake via bakery food was 0.049 g·d -1 in Beijing and Guangzhou city,energy contribution was 0.027% which was far below the WHO reco mmended level (1 %). Population that are 3 to 6 years old had highest TFA intake and the TFA energy contribution was 0.041 %.CONCLUSION Most of bakery products in China contained low levels of TFA;consequently, health risk caused by TFA intake in Beijing and Guangzhou was unlikely to be a concerned.However, so me type of bakery foods had higher TFA contents which could be of greater concerned for risk management.

Study on toxicity of hyperoside in rat embryo-fetal development / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the toxicity of hyperoside in rat embryo-fetal development, in order to provide preference for safe use of drugs during gestation period.</p><p><b>METHOD</b>Healthy pregnant rats were randomly divided into hyperosid groups (30, 175, 1000 mg x kg(-1) x d(-1)), the positive control group (cyclophosphamide, 7 mg x kg(-1) x d(-1)) and the solvent control group (1% aqueous carboxymethylcellulose). These rats were orally administered with hyperosid or vehicle during 6-15 d after gestation and subcutaneously injected with cyclophosphamide during 11-13 d. Maternal clinical sign, abortions, premature deliveries and body weight were monitored throughout gestation. At termination (gestation days 20), pregnant females were evaluated for clinical symposiums, weight change, corpora lutea count, existence and death of embryos; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.</p><p><b>RESULT</b>All pregnant rats showed no significant abnormality in appearance, viscera and skeletal development. However, there was a difference between the high-dose group of hyperoside and negative control group in the fetus body weight, the length of the embryos and the length of tail (P < 0.05).</p><p><b>CONCLUSION</b>Pregnant women are suggested to cautiously use hyperoside because it shows certain impact on development of fetal rats under the experimental conditions.</p>

Isolation, Purification and Characterization of Human Serum Apolipoprotein A Ⅰ / 中国基层医药

Objective To explore a method to separate and purify apolipoprotein Ⅰ from human serum conveniently and efficiently. Methods Apolipoprotein Ⅰ was separated and pufified by ultracentrifugation and affinity chromatography. Then the purified apolipoprotein Ⅰ was analyzed by SDS-polyacrylamide gel electrophoresis and agar gel double immunodiffusion test. Results The purified apolipoprotein Ⅰ was satisfactory. Conclusion This method had good reliability and was convenient and economical.

Sensitivity in typeⅠ hypersensitivity compared between BN rats and Wistar rats / 中国药理学与毒理学杂志

OBJECTIVE To compare sensitivity in typeⅠ hypersensitivity between BN and Wistar rats, and to establish a sensitive and reliable determination system for typeⅠ hypersensitivity. METHODS BN and Wistar rats were sc given ovalbumin (OVA) 10, 20 and 40 μg·kg~(-1) every other day for 5 times and normal control group with sc normal saline. The total immunoglobulin E (IgE) levels in serum were determined with ELISA and the specific IgE levels in serum were determined by passive cutaneous anaphylaxis on the 21st day from the 1st injection. The blood pressure, serum histamine and tryptase levels were determined after challenge on the 22nd day. RESULTSTotal IgE, specific IgE, histamine and tryptase levels in serum significantly increased and blood pressure decreased in OVA 10, 20 and 40 μg·kg~(-1) BN rat groups compared with normal control group, while in Wistar rats these symptoms only appeared in OVA 40 μg·kg~(-1) group. CONCLUSION BN rats are more sensitive than Wistar rats in typeⅠ hypersensitivity. The blood pressure, serum total IgE, specific IgE, histamine and tryptase levels can be used as the important indicators in typeⅠ hypersensitivity.

Safety evaluation of traditional Chinese medicine injections and study of related key technology / 中国中药杂志

Traditional Chinese medicine (TCM) injections originated in China and have been extensively used in clinic. However, some events the adverse drug reactions (ADRs) have been reported, among which, hypersensitivity reactions (HSRs) are the main ADRs of TCM injections. To solve the ADRs of TCM injections will be the key to proceed of the modernization of TCM. This paper reviewed the current situation and causes of the ADRs of TCM injections. On the basis of primary findings obtained from the project granted by the Ministry of Science and Technology, two pivotal technologies of the safety evaluation of TCM injections were introduced, which are anaphylactoid reaction ussessment and metabonomics for TCM injections. It is expected to provide some new ideas for the breakthrough of the safety evaluation of TCM injections.

Profile and prevalence of aspirin resistance in patients with metabolic syndrome / 老年心脏病学杂志（英文版）

Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease,particularly for subjects at high risk such as metabolic syndrome.However,the responsiveness to aspirin treatment may vary among individuals.The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome.Methods In 221 consecutive patients,platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d).Aspirin resistance was defined as mean optical platelet aggregation =20%.Results Aspirin resistance occurred in 39 patients (17.6%).Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6_+0.4g/l vs 2.4±0.4g/L,P=0.017).The 2 groups,aspirin resistance group and no aspirin resistance group,did not differ significantly,with regard to gender,age,body mass index,waist-hip ratio,blood pressure level,serum cholesterol level and history of myocardial or cerebral infarction.Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973,p=0.023).Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%,P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%,P=0.043).But after multifactor logistic regression,in women blood pressure=85mmHg was not a predictor any more.Conclusions In patients with metabolic syndrome,aspirin resistance is not uncommon,especially for men with history of myocardial infarction.Patients with aspirin resistance have an increased serum fibrinogen level.(J Geriatr Cardio12008;5:7-10)

Clinical study of aspirin resistance in patients with metabolic syndrome / 中国实用内科杂志

Objective To investigate the prevalence of aspirin resistance(AR)in the patients with metabolic syndrome and the clinical characteristics.Methods A total of 221 patients with metabolic syndrome received 200 mg of aspirin daily for 10 days and no other antiplatelet agent.The blood samples were analyzed by platelet aggregation test(pAgT)using arachidonic acid(AA).We identified aspirin resistance when arachidonic acid induced aggregation≥20%.Results 17.6%of the patients showed AR.The AR fibrinogen level was significantly higher than AS patients(2.6?0.4 vs 2.4?0.4,P=0.017).Patients who were AR had no statistically significant difference in blood pressure,age,fasting blood glucose,blood fat and BMI compared with aspirin-sensitive patients(AS).There was also no difference in sex,smoking and history of myocardial infarction or ischemic stroke between AR and AS patients.When stratified by sex,we found history of myocardial infarction was predictor for AR in male(50.0% vs 14.5%,P=0.020)and so was diastolic blood pressure higher than 85mmHg in female(34.0% vs 15.5%,P=0.043).Conclusion The AR accounts for 17.6%(39/221)of all.In this research.AR patients have higher level of fibrinogen than AS.History of myocardial infarction and higher level of diastolic blood pressure may be the predictor for AR in male and female individually.

Gene theory-based intervention: the effect of up-regulating microsatellite polymorphism in heme oxygenase-1 gene promotor / 中国组织工程研究

BACKGROUND: Heme oxygenase-1 (HO-1) promotor region has a pair of dinucleotide(guanosine thymidine, GT) repeats with a lengthy polymorphism, also named microsatellite polymorphism. Experiments in vitro have shown that we can indirectly learn about the level of gene transcription by measuring the number of GT repeats.OBJECTIVE: To investigate if an association exists between restenosis after percutaneous coronary intervention(PCI) and microsatellite polymorphism in HO-1 gene promoter.DESIGN: A case-control study based on the observation of the patients with coronary heart disease after undergoing coronary stenting.SETTING: Wards of the department of cardiology of a university hospital.PARTICIPANTS: A total of 118 patients were admitted from April 1996 to May 2002 at the Department of Cardiology of the First Hospital of Peking University who underwent successful coronary stenting. Inclusion criteria: The patients with coronary heart disease who underwent coronary stent implantation for more than 3 months now came to perform coronary angiography in follow-up. Exclusion criteria: Angiography showed that the stenosis of lumen in diameter in the patients with coronary heart disease was less than 50%and the follow-up in angiography was less than three months. There were 92males and 26 females aged(62±10) years old and the informed consents were obtained. The patients were divided into two groups according to the criteria stipulated by American Heart,Lung and Blood Association: in-stent restenosis(68 cases) and non-restenosis (50 cases).METHODS: DNA of the peripheral blood was isolated from the whole blood. The length of GT repeat was confirmed by PCR amplification and Spreadex Gel electrophoresis. Selected samples were sequenced with Sanger's method.MAIN OUTCOME MEASURES: Microsatellite gene frequency of HO-1promoter and its relationship with restenosis RESULTS: Patients with GT repeats <25 GT in the HO-1 gene promoter on either allele had significantly less often restenosis than patients without (47.5% vs. 68.4% ,P<0.05). After controlling some possible confound ing factorsfor coronary heart diseases, multivariate analysis indicated that still there was a significant difference between the two groups in restenosis rate(odd ratio 0. 418,95% CI: 0. 197 to 0. 887,P<0.05).CONCLUSION: The present study indicated that short(GT) n repeats of HO-1 gene promoter is associated with reduced post-PCI restenosis, which suggests the genetic contribution to in-stent restenosis after stent implantation. It may have important meanings to prevent the occurrence of restenosis.

Premature coronary heart disease in female:clinical and coronary angiography features / 中国介入心脏病学杂志

Objective To explore the clinical and coronary angiography features of female patients suffering from premature coronary heart disease by analyzing retrospectively the clinical data of those women who undertook coronary angiography before 55 years old in a period of 5 years. Methods Female patients under 55 years were enrolled. Data such as risk factors (including hypertension, diabetes, hyperlipidemia, stroke, and metabolic syndrome), clinical findings (including blood pressure, serum lipid test on admission), and coronary angiographic images were collected to find the relationship between risk factors and coronary heart disease. Results The study had enrolled 166 cases with 71 cases (42.8%) of them diagnosed as coronary heart disease. In this group, the most important risk factors were diabetes, metabolic syndrome, history of hypertension, high level of serum TG and decreased HDL. At the same time, we found that the body mass index, LDLC level, TG level and blood glucose in CHD patients were significantly higher than those in non-CHD ones. Single vessel disease was the most popular pattern of these CHD patients. Conclusion History of diabetes, metabolic syndrome and hypertension were the most vital risk factors of CHD in this relative young female population.

Factors influencing outcomes of patients with acute myocardial infarction receiving primary percutaneous coronary intervention / 中国介入心脏病学杂志

360 min,the risk of no-reflow phenomenon was decreased in patients with SOTB≤360 min(OR=0.2,95% CI:0.0-1.0,P=0.045).(2) Obesity was identified as an independent risk factor for peak concentration of CK-MB(?=117.3,95% CI:12.1-222.6,P=0.029).(3) Age(above 60 years old),obesity,and preprocedural Killip classification were identified as independent risk factors for postprocedural LVEF.Old age(?=-6,95% CI:-9.7--2.2,P=0.002) and obesity(?=-3.8,95% CI:-7.6--0.1,P=0.044)were associated with low LVEF but preprocedural cardiac function of Killip Class Ⅰ was associated with high LVEF(?=4.9,95% CI:0.4～9.4,P=0.033).(4) Preprocedural Killip classification and multivessel disease were independent predictors for major adverse cardiac event in the follow-up period.The risk of major adverse cardiac event during follow-up decreased in patients with preprocedural Killip class I compared with patients with Killip class Ⅱ~Ⅳ(OR=0.1,95% CI:0.0-0.7,P=0.022),but the risk increased in patients with multivessel disease compared with those who had single vessel disease(OR=10.5,95% CI:1.1-99.4,P=0.041).Conclusion The clinical outcomes and prognosis of patients with AMI treated with primary PCI were associated with a variety of risk factors including age,obesity,multivessel disease,and preprocedural cardiac function.In addition,SOTB was related to postprocedural TIMI flow in patients with AMI undergoing primary PCI.

Cholesterol crystal embolism after coronary intervention / 中国介入心脏病学杂志

Objective To analyze the clinical characteristics of patients with cholesterol crystal embolism (CCE) after percutaneous coronary intervention. Methods Six patients with atherosclerosis presenting with simultaneous occurrence of acute renal failure and peripheral ischemic changes were diagnosed as cholesterol crystal embolism and their clinical data were analyzed. Results The patients, 5 men and 1 woman, had an average age of 72 years. Most of them had risk factors of atherosclerosis such as hypertension, diabetes and smoking. The levels of serum creatinine increased progressively after coronary angiography. All patients had concomitant skin lesions, including blue toes. Cutaneous biopsy of 1 patient found cholesterol emboli in arterioles. All patients received statins, and 2 received dialysis. Three patients died, and 3 patients remained chronic renal failure. Conclusion Since the morbidity of CCE is growing and the disease is iatrogenic in origin, special attention should be paid to this disease.