Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.     

孕期胆固醇和氧化固醇与子代认知发育

胆固醇是大脑发育的重要物质基础,胚胎和胎儿发育需要母体持续转运胆固醇,氧化固醇是胆固醇的代谢物,包括胆固醇合成途径中的前体物和分结代谢过程中产生的代谢产物,可能与大脑功能密切相关。人群研究发现,孕妇血清/浆胆固醇水平与子代多动症、孤独症谱系障碍发病风险有关,但尚需进一步确证。     

维生素D缺乏性晚发性佝偻病的骨密度研究

目的：探讨维生素D缺乏性晚发性佝偻病的骨密度变化;方法：采用病例对照研究方法。对640名学生进行问诊及体验,测定非优势侧尺挠骨中1／3交界处骨密度（BMD）,病例组检测骨碱性磷酸酶,拍摄腕部X光片,病例组与对照组同测血250HD3;结果：病例组骨密度显著低于对照组,病例组250HD3异常者显著低于对照组;结论：晚佝病是由于维生素D缺乏所至的骨量减少性疾病,日后影响峰值骨量的形成,并与成人期骨质疏松有密切的关系,骨密度检查对晚佝病有重要诊断价值。     

基于肠道菌群和代谢组学研究化滞柔肝颗粒治疗非酒精性脂肪肝的作用机制

目的 探讨化滞柔肝颗粒治疗非酒精性脂肪肝（nonalcoholic fatty liver disease,NAFLD）的作用机制。方法 高脂饮食饲养8周构建大鼠NAFLD模型,化滞柔肝颗粒ig给药4周。半自动生化分析仪测定大鼠血脂相关指标;油红O染色观察肝脏组织病理变化;Illumina Miseq测序平台对V3～V4可变区进行扩增和测序,超高效液相色谱串联质谱（UPLCMS/MS）开展血浆代谢组学研究,并结合Spearman进行肠道菌群与代谢组学之间的关联分析。结果 与模型组相比,化滞柔肝颗粒中、高剂量组可显著降低大鼠体质量（P<0.05、0.01）和血清总胆固醇（totalcholesterol,TC）、三酰甘油（triacylglycerol,TG）水平（P<0.01）,升高高密度脂蛋白（high-density lipoprotein cholesterol,HDL-C）水平（P<0.05、0.01）。此外,化滞柔肝颗粒高剂量组还可显著降低大鼠低密度脂蛋白（low-density lipoprotein cholesterol,LDL-C）水平（P<0...     

Site of bone density measurement may affect therapy decision

Summary The purpose of this study was to determine whether bone mineral density (BMD) measurements at the lumbar spine and femoral neck provided comparable information to women planning to use that knowledge to help them make a decision about hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44–59 and within 0 to 5 years of menopause, participated in the study. BMD measurements were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X-ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis Foundation were used to categorize women as at risk for osteoporosis, bone density more than one standard deviation (SD) below the young adult mean, or as low risk, bone density at or above this level. The re that 46 women would be classified into the low risk category on the basis of spinal BMD alone. However, 28 of these 46 women would fall into the at risk category when the femoral neck BMD was measured. Sixty-one percent of women informed they were at low risk on the basis of spinal BMD would be considered at risk based on femoral neck BMD. When femoral neck BMD was used as the primary risk indicator, 14% of the women classified as low risk would be at risk if spinal BMD were added. These results suggest that both lumbar spine and proximal femur measurements should be made when women are using bone density measurements as an aid in deciding whether or not to use hormone therapy in their postmenopausal years.     

贵阳地区1?055例骨密度检测分析

采用日本阿洛卡公司双能量骨密测量仪,选择受检者桡骨远端１／３处为测量点,对贵阳地区１０５５例人群成人桡骨的骨密度进行测量,取得不同性别各年龄段的骨密度值,同时计算出贵阳地区成人桡骨各年龄段的骨密度均值及标准偏差。     

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

1. 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.
2. PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K_i of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the K_i.
3. Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg⁻¹, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated K_i (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.
4. The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.
5. PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg⁻¹ (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.
6. Results of these studies are consistent with a role for 15-LO in atherogenesis.

     

Low serum cholesterol increases the risk of noncardiovascular events: An antagonist viewpoint

Summary Considerable debate concerning the apparent association of low serum cholesterol levels with enhanced noncardiovascular disease mortality has been aired in both scientific and lay publications within the past year. This debate has resulted in some medical experts calling for a moratorium on efforts to reduce serum cholesterol, particularly with drugs, and for a more conservative approach to screening and modifying cholesterol levels for the primary prevention of coronary heart disease (CHD). Observational studies, including the Framingham Heart Study, the Multiple Risk Factor Intervention Trial, the Whitehall Study, and the International Collaborative Group, have not substantiated a cause and effect relationship between naturally occurring low serum cholesterol and noncardiovascular disease mortality, such as cancer. Intervention trials designed to lower high serum cholesterol levels by diet and drugs have also not been conclusively shown to produce excess harm that offsets the benefit of reduced CHD events. Several primary and secondary CHD prevention trials, with sufficient numbers of subjects to provide the statistical power to detect potential detrimental effects of lowering cholesterol levels, are currently in progress and will be very helpful in resolving the concern about noncardiovascular disease mortality.     

Characteristics of bone mineral density and soft tissue composition of obese Japanese women: Application of dual-energy X-ray absorptiometry

We studied the characteristics of bone mineral density (BMD) and soft tissue composition in obese Japanese women using dual-energy X-ray absorptiometry. Eighty-nine women, aged 45–85 years, were divided into three groups according to their body mass index (BMI): a thin group (n = 38; BMI < 21), a standard weight group (n = 31; BMI, 21–25), and an obese group (n = 20; BMI ≥ 25). The mean BMD of the second to fourth lumbar vertebrae and BMD of the lumbar spine, thoracic spine, pelvis, legs, and ribs of the thin group were significantly lower than those of the standard weight group or the obese group (P < 0.05), whereas no significant difference in total body BMD was observed among the three groups. There was a significant difference in total and regional fat mass among the three groups (P < 0.05). Lean mass of legs and total lean mass showed a significant difference between the thin group and the obese group (P < 0.05). The results showed that obesity was associated with higher BMD of weight bearing-bones and ribs, high total and regional fat mass, and high lean mass of bilateral legs and total lean mass. We suggest that obesity may contribute to the prevention of bone loss of weight-bearing bones and ribs and muscular atrophy of the legs. Received: Sept. 30, 1998 / Accepted: Dec. 10, 1998