Quantitative efficacy of soy isoflavones on menopausal hot flashes

AIM

This study aimed to quantitate the efficacy of soy isoflavones in the treatment of menopausal hot flashes.

METHODS

Model based meta-analysis (MBMA) was used to quantitate the efficacy of soy isoflavones. We conducted a systemic literature search to build a time–effect model for placebo and soy isoflavones in treating menopausal hot flashes. Studies were identified, subjected to inclusion and exclusion criteria, and reviewed.

RESULTS

From 55 articles, 16 studies of soy isoflavones met the inclusion criteria, and contained 65 and 66 mean effect values in placebo and soy isoflavone groups, respectively, from about 1710 subjects. Interestingly, the developed model was found to describe adequately the time course of hot flashes reduction after administration of placebo and soy isoflavones. Using this model, we found that the maximal percentage change of hot flashes reduction by soy isoflavones was 25.2% after elimination of the placebo effect, accounting for 57% of the maximum effects of estradiol (E_{max-estradiol} = 44.9%). However, a time interval of 13.4 weeks was needed for soy isoflavones to achieve half of its maximal effects, much longer than estradiol, which only required 3.09 weeks. These results suggest that treatment intervals of 12 weeks are too short for soy isoflavones, which require at least 48 weeks to achieve 80% of their maximum effects.

CONCLUSIONS

Soy isoflavones show slight and slow effects in attenuating menopausal hot flashes compared with estradiol.     

Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring.

Perfluorooctanoic acid (PFOA), with diverse and widespread commercial and industrial applications, has been detected in human and wildlife sera. Previous mouse studies linked prenatal PFOA exposure to decreased neonatal body weights (BWs) and survival in a dose-dependent manner. To determine whether effects were linked to gestational time of exposure or to subsequent lactational changes, timed-pregnant CD-1 mice were orally dosed with 5 mg PFOA/kg on gestation days (GD) 1-17, 8-17, 12-17, or vehicle on GD 1-17. PFOA exposure had no effect on maternal weight gain or number of live pups born. Mean pup BWs on postnatal day (PND) 1 in all PFOA-exposed groups were significantly reduced and decrements persisted until weaning. Mammary glands from lactating dams and female pups on PND 10 and 20 were scored based on differentiation or developmental stages. A significant reduction in mammary differentiation among dams exposed GD 1-17 or 8-17 was evident on PND 10. On PND 20, delays in normal epithelial involution and alterations in milk protein gene expression were observed. All exposed female pups displayed stunted mammary epithelial branching and growth at PND 10 and 20. While control litters at PND 10 and 20 had average scores of 3.1 and 3.3, respectively, all treated litters had scores of 1.7 or less, with no progression of duct epithelial growth evident over time. BW was an insignificant covariate for these effects. These findings suggest that in addition to gestational exposure, abnormal lactational development of dams may play a role in early growth retardation of developmentally exposed offspring.     

Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor.

The estrogenic isoflavone genistein is a common dietary component that has been shown to affect reproductive development in experimental animals at high doses. The objective of the present study was to examine interactions of genistein and the hormonally active pesticide methoxychlor on mammary gland development in juvenile rats. Timed-pregnant Sprague-Dawley rats were fed a soy- and alfalfa-free diet containing different combinations of genistein (300 and 800 ppm) and methoxychlor (800 ppm). Rats were fed these diets starting on gestation day (GD)1 and continuing through pregnancy and lactation until postnatal day (PND) 22, when the pups were killed. Inguinal mammary glands from both female and male pups were processed as whole-mount preparations for morphometric analysis. The total glandular area and the numbers of branch points, lateral buds, and terminal end buds in the male rats were found to be significantly greater in the groups exposed to methoxychlor than those exposed to genistein only. These effects were not observed in the female rats. In the male rats, methoxychlor had the most prominent effect on elongating the glandular ducts, while genistein enhanced the ductile branching. The 2 compounds in combination promoted the development of alveolar-lobular structure, an effect not observed with either compound alone. Immunostaining for proliferating cell nuclear antigen revealed a high percentage of immunopositive cells in the mammary epithelia of the males exposed to methoxychlor and genistein (800 ppm) compared to the controls. While no significant changes in serum levels of mammotrophic hormones were detected, increased immunostaining for insulin-like growth factor-1 receptor, estrogen receptor alpha, and progesterone receptor in the genistein + methoxychlor group suggested that local factors involved in regulating mammary growth may have played a role in propagating the endocrine effects of these two compounds. These results indicated that the mammary glands of juvenile male rather than juvenile female rats may be more sensitive to certain endocrine-active compounds and that high levels of phytoestrogens have the potential to alter the toxicological behaviors of other hormone mimics.     

Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth.

Prenatal exposure to 100 mg/kg atrazine (ATR) delays mammary gland (MG) development in resulting female offspring of Long-Evans rats. To determine if the fetal MG was sensitive to ATR effects during specific periods of development, timed-pregnant dams (n = 8/group/block) were dosed for 3- or 7-gestation day (GD) intervals (GD 13-15, 15-17, 17-19, or 13-19) with 100 mg ATR/kg/day or vehicle (C), and their offspring were evaluated for changes. Mammary glands taken from pups prenatally exposed to ATR displayed significant delays in epithelial development as early as postnatal day (PND) 4 compared to C, with continued developmental delays at later time points that varied by time of exposure. However, the most persistent and severe delays were seen in the GD 17-19 and GD 13-19 ATR exposure groups, demonstrating statistically similar growth retardation. Because MG developmental deficits persisted into adulthood, we hypothesized that ATR-exposed animals may have had difficulties nursing their young. Females exposed prenatally to either ATR (as defined) or C (n = 4 litters/group) were bred, and the resulting F(2) offspring from GD 17-19 and GD 13-19 exposure groups were significantly smaller in body weight (BW) than C. In a separate study, it was determined that ATR (25-100 mg/kg), delivered from GD 15-19, did not decrease fetal body weights on GD 20, even though the higher doses significantly decreased weight gain of the dosed dams. These data suggest that the consequences of brief ATR exposure during a critical period of fetal MG development (GD 17-19), are both delayed MG development of the offspring and inadequate nutritional support of F2 offspring, resulting in adverse effects on pup weight gain.     

三种治疗方案用于乳腺癌化疗的成本—效果分析

OBJECTIVETo analyze and evaluate three chemotherapeutic programs for mammary gland carcinoma for rational use of drugs. METHODSUsing pharmacoeconomic cost-effectiveness analysis. RESULTSAmong three programs,I,e PP,FAC,IFAF, the effective rate of PP was 80     

喉罩通气在乳腺手术中的运用

目的:探讨采用喉罩通气的方法在乳腺良性肿瘤手术中的应用.方法:选择乳腺良性肿瘤手术患者20例,麻醉诱导后置入喉罩,术中异丙酚,瑞芬,阿曲库胺维持麻醉,分别在麻醉前、手术前及手术后40 min监测分钟通气量、呼气末二氧化碳分压、动脉血气及麻醉并发症.结果:手术前分钟通气量,呼气末二氧化碳分压,pH及PaCO2较麻醉前明显降低(P＜0.05),并超过正常范围,但与手术后40 min相比差异无显著性(P＞0.05).20例患者在术中均未出现反流误吸及呛咳.术后随访3例(7%)诉有咽喉疼痛.结论:喉罩是集合面罩与气管内导管优点的通气设备,可以在乳腺手术中得到推广使用.     

Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure during gestation has revealed reproductive anomalies in rat offspring, including inconclusive reports of stunted mammary development in females (Brown et al., 1998, Carcinogenesis 19, 1623-1629; Lewis et al., 2001, TOXICOL: Sci. 62, 46-53). The current studies were designed to examine mammary-gland development in female offspring exposed in utero and lactationally to TCDD, and to determine a critical exposure period and cellular source of these effects. Long-Evans rats were exposed to 1 microg TCDD/kg body weight (bw) or vehicle on gestation day (GD) 15. TCDD-exposed females sacrificed on postnatal days (PND) 4, 25, 33, 37, 45, and 68 weighed significantly less than control litter mates, and peripubertal animals exhibited delayed vaginal opening and persistent vaginal threads, yet did not display altered estrous cyclicity. Mammary glands taken from TCDD-exposed animals on PND 4 demonstrated reduced primary branches, decreased epithelial elongation, and significantly fewer alveolar buds and lateral branches. This phenomenon persisted through PND 68 when, unlike fully developed glands of controls, TCDD-exposed rats retained undifferentiated terminal structures. Glands of offspring exposed to TCDD or oil on gestation days 15 and 20 or lactation days 1, 3, 5, and 10 were examined on PND 4 or 25 to discern that GD 15 was a critical period for consistent inhibition of epithelial development. Experiments using mammary epithelial transplantation between control and TCDD-exposed females suggested that the stroma plays a major role in the retarded development of the mammary gland following TCDD exposure. Our data suggest that exposure to TCDD prior to migration of the mammary bud into the fat pad permanently alters mammary epithelial development in female rat offspring.     

妇康宁治疗良性乳腺增生73例临床分析

目的 探讨妇康宁治疗良性乳腺增生的临床效果.方法 2010年3月～2013年3月对136例良性乳腺增生患者应用妇康宁及乳癖消治疗3年追踪观察分析.结果 对于服用乳癖消的对照组63例良性乳腺增生患者中,彻底治愈10例,其余均未彻底治愈.而服用妇康宁的治疗组73例良性乳腺增生患者中,彻底治愈59例,乳腺结节明显减小14例.两组临床效果比较,差异有统计学意义（P＜0.01）.结论 妇康宁治疗良性乳腺增生疗效确切.     

大豆异黄酮对成年大鼠脑缺血再灌注的影响

目的:观察大豆异黄酮对脑缺血再灌注大鼠海马神经再生的影响。方法:线栓法建立成年大鼠脑缺血再灌注模型,分别给予大豆异黄酮(SI)或联合给予他莫昔芬(tamoxifen,TX)和SI,BrdU免疫荧光法标记新生海马神经细胞,免疫组化法和western blot检测海马区phosphorylated CREB(pCREB)的表达。结果:大豆异黄酮(SI)组和联合给药(SI+TX)组大鼠海马区BrdU+细胞数显著增加(与模型组比,P<0.01),且SI组大鼠海马区BrdU+细胞数明显多于SI+TX组(P<0.05)。SI组大鼠海马区BrdU+/pCREB+的细胞数量明显增多,pCREB的表达也明显增加(与模型组比较,P<0.05);SI+TX组大鼠海马区BrdU+/pCREB+的细胞数量明显减少(与大豆异黄酮组比较,P<0.05),pCREB的表达明显减少(与模型组比,P<0.05)。结论:长期给予大豆异黄酮可以使脑缺血再灌注海马神经再生,这种作用可能与其雌激素活性、促进CREB的磷酸化以维持神经再生、存活或修复的信号有关。     

A novel effect of dioxin: exposure during pregnancy severely impairs mammary gland differentiation.

Many ligands for the aryl hydrocarbon receptor (AhR) are considered endocrine disruptors and carcinogens, and assessment of adverse health effects in humans exposed to such chemicals has often focused on malignancies, including breast cancer. Mammary tissue contains the AhR, and inappropriate activation of the AhR during fetal development causes defects in mammary development that persist into adulthood. However, it is not known whether the extensive differentiation of mammary tissue that occurs during pregnancy is also sensitive to disruption by AhR activation. To examine this, we exposed pregnant C57Bl/6 mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on days 0, 7, and 14 of pregnancy. Examination of mammary glands on days 9, 12, and 17 of pregnancy and on the day of parturition showed severe defects in development, including stunted growth, decreased branching, and poor formation of lobular alveolar structures. This impaired differentiation was biologically significant, as expression of whey acidic protein in the gland was suppressed, and all pups born to TCDD-treated dams died within 24 h of birth. Analysis of circulating progesterone, prolactin, and estradiol suggest that hormone production was slightly impaired by inappropriate activation of the AhR. However, hormone levels were affected only very late in pregnancy. Given that the observed defects in gland development preceded these hormonal effects, altered hormone levels are an unlikely mechanistic explanation for impaired mammary development. This novel finding that AhR activation during pregnancy disrupts mammary gland differentiation raises questions about the susceptibility of mammary tissue to direct injury by endocrine disrupting agents and the potential for AhR-mediated signaling to adversely affect lactation and breast tissue development in human populations.     

大豆异黄酮对去卵巢大鼠骨密度和雌激素活性的影响(英文)

目的 :研究大豆异黄酮对去卵巢大鼠骨密度以及雌激素活性的影响。方法 :将 10～ 12月龄的雌性Wistar大鼠随机分为 6组 :假手术组 (SHAM )、切卵巢模型组 (OVX)、尼尔雌醇组 (OVX E)、小剂量异黄酮组 (L ISO)、中剂量异黄酮组 (M ISO)、大剂量异黄酮组 (H ISO) ,每组 8只。后 5组大鼠被切除双侧卵巢 ,SHAM组只被切除卵巢附近脂肪组织。L ISO ,M ISO ,H ISO分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1的大豆异黄酮 ,OVX E组大鼠灌胃给予0 .2mg·kg- 1·wk- 1的尼尔雌醇 ,SHAM与OVX组以等剂量的溶剂灌胃 ,15wk后股动脉放血处死动物 ,收集血液用于血清碱性磷酸酶活性、血清雌二醇水平、血钙、血磷测定 ,分离出右侧股骨、第 2腰椎用于骨密度测量 ,测定双侧子宫重量。结果 :与SHAM组相比 ,OVX组股骨骨密度和椎骨骨密度均可见不同程度降低 (P <0 .0 5和P >0 .0 5 ) ,尼尔雌醇与异黄酮 12 0mg·kg- 1能明显升高去卵巢大鼠的股骨和椎骨骨密度 (P <0 .0 5 )。OVX组的血清碱性磷酸酶水平高于SHAM组 (P <0 .0 5 ) ,异黄酮6 0mg·kg- 1可降低去卵巢大鼠的血清碱性磷酸酶水平 (P <0 .0 5 )。OVX组的血清雌二醇水平与子宫系数明显低于SHAM组 (P <0 .0 1) ,异黄酮的不同剂量组与OVX E组的血清雌二醇水平、子宫系数都明显高于OV     

模式识别在乳腺病变鉴别诊断中的应用

本文以细胞核六项参数为指标,用模式识别对正常活动期乳腺及其良恶性病变(纤维腺瘤、单纯性增生、不典型增生和乳腺癌,进行判别分析。结果证明,细胞核形态参数的模式识利为鉴别诊断乳腺疾病提供了简单而准确的手段。     

Altered mammary gland differentiation and progesterone receptor expression in rats fed soy and whey proteins.

There are suspected links between an animal's diet, differentiation status of a target tissue, and sensitivity to chemically induced cancer. We have demonstrated that rats fed AIN93G diets made with soy protein isolate (SPI) or whey protein hydrolysate (WPH) had a lower incidence of 7,12-dimethylbenz(a)anthracene (DMBA)-induced adenocarcinoma than rats fed the same diet made with casein (CAS). The current study was conducted to determine the differentiation status of the mammary glands during development. Offspring of rats (n = 5-10/group) were fed diets made with SPI, WPH, or CAS throughout life (beginning on gestation day 4) and were sacrificed on postnatal day (PND) 21, PND 33, PND 50 or on metaestrous between PND 48 and PND 51. There were no significant differences between the numbers of mammary terminal end buds (TEBs) or lobuloalveoli (LOB) between any of the diets groups at PND 21 or PND 33, but at PND 50 there was an 75% decrease in the mean numbers of TEBs/mm(2) in the SPI- or WPH-fed rats, compared with the CAS-fed rats (p = 0.09 and p = 0.06, respectively). In rats sacrificed in metaestrous, there were no significant differences in the proliferation index (PI) in the TEBs or LOB between any of the diet groups. In metaestrous rats, there were twice as many cells expressing estrogen receptor beta (ERbeta; approximately 60%) compared with estrogen receptor alpha (ERalpha; approximately 30%) in the LOB and 1.5 times more ERbeta (approximately 60%) compared with estrogen receptor alpha (ERalpha, approximately 40%) in the TEBs. There were no diet-dependent differences in expression of ERalpha and ERbeta. Similarly, there were no differences between the diet groups in progesterone receptor (PR) expressing LOB cells. However, in the TEBs there was a diet-dependent difference in PR positive cells with a 34% increase (p < 0.05) in the SPI-fed rats and a 38% increase (p < 0.05) in the WPH-fed rats compared with the CAS-fed rats. These results show that the type of dietary protein alters the phenotype of mammary epithelia in the TEBs. The SPI- and WPH-dependent changes in mammary differentiation may contribute to the reduced sensitivity to DMBA-induced mammary cancer in rats fed these proteins.     

玫瑰花总黄酮对乳腺增生大鼠上皮-间质转换的影响

目的： 探讨玫瑰花总黄酮对实验性乳腺增生大鼠上皮-间质转换（EMT）的影响。方法： 通过注射雌激素和孕激素诱导大鼠乳腺增生,观察玫瑰花总黄酮（200和100 mg·kg^-1·d^-1）给药干预对乳腺组织形态学变化、乳腺fibronectin、α-SMA、E-cadherin、collagen-I和TGF-β1表达情况,以及微小RNA（miR）-21和miR-29a/b水平的影响。结果： 玫瑰花总黄酮给药能显著改善模型动物乳腺增生的趋势,抑制乳腺组织collagen-I沉积和TGF-β1表达,缓解EMT上皮标记物E-cadherin的缺失以及间质标记物fibronectin和α-SMA等的过度表达,降低miR-21并一定程度恢复miR-29a/b的水平。结论： 玫瑰花总黄酮对乳腺EMT发生的程度具有潜在的抑制作用。     

乳增宁胶囊治疗乳腺增生症120例报告

1999年7月～2000年7月经我院门诊治疗乳腺增生症患者120例,采用中药乳增宁胶囊进行治疗,效果较满意,现报告如下.     

数字化乳腺摄影在福田区适龄女性乳腺癌筛查中的价值研究

目的 探讨数字化乳腺摄影在福田区适龄女性乳腺癌筛查中的价值.方法 对福田区2451名适龄女性采用数字化乳腺摄影进行乳腺癌筛查,采用数字化钼靶拍片机,对所有筛查者常规摄取双乳轴位、侧斜位片,由两名放射科主治医师进行读片诊断.结果 所有筛查对象中,乳腺呈脂肪型443例（18.1％）、少腺体型821例（33.5％）、多腺体型984例（40.1％）、致密型203例（8.3％）;乳腺摄影结果：0级249例（10.16％）、Ⅰ级2042例（83.31％）、Ⅱ级78例（3.18％）、Ⅲ级71例（2.90％）、Ⅳ级9例（0.37％）、V级2例（0.08％）;共筛查出6例乳腺癌患者,脂肪型乳腺1例,少腺体型乳腺2例,多腺体型乳腺2例,致密型乳腺1例.结论 数字化乳腺摄影的图像清晰,密度分辨率及空间分辨率高,对乳腺癌的敏感性强,可作为福田区适龄女性乳腺癌筛查首选的影像学方法.     

柴胡疏肝汤对实验性乳腺增生大鼠的治疗作用

目的通过动物实验验证柴胡疏肝汤抗乳腺增生的作用。方法成熟雌性大鼠每天腹腔注射苯甲酸雌二醇0.8mg.kg-1,连续注射25d,继而连续5d腹腔注射黄体酮4mg.kg-1,造成乳腺增生模型。灌服柴胡疏肝汤提取液30d,末次给药1h,测定第二对乳头高度及直径,采血测定血清中雌激素和孕激素水平。结果柴胡疏肝汤能抑制模型大鼠的乳头高度及直径,降低造模大鼠血清中雌激素水平。结论柴胡疏肝汤对大鼠实验性乳腺增生具有明显的治疗作用。     

大豆异黄酮对高胆固醇血症大鼠血及肝脏MDA含量和SOD活力的影响(英文)

目的 :研究大豆异黄酮对高胆固醇血症大鼠血液及肝脏丙二醛 (MDA )、超氧化物歧化酶(SOD)的影响。方法 :根据血胆固醇水平 ,5 0只雄性Wistar大鼠随机分为 5组 ,正常对照组 (NC)、高胆固醇血症对照组 (HC)和 3个大豆异黄酮治疗组。除正常对照组以外 ,各组均喂以高胆固醇饲料。同时 ,3个治疗组分别灌胃给予 30 ,6 0 ,12 0mg·kg- 1大豆异黄酮 ,对照组给予相应的溶媒 ,持续 9wk。实验结束时 ,分离血清、红细胞 ,取出肝脏 ,制备肝匀浆。采用黄嘌呤氧化酶法测定红细胞和肝匀浆SOD活力 ,以硫代巴比妥酸法测定血清和肝匀浆MDA含量。结果 :与正常对照组比较 ,高胆固醇血症对照组大鼠红细胞及肝匀浆SOD活力明显降低。大豆异黄酮 6 0和 12 0mg·kg- 1组大鼠红细胞及肝脏SOD活力比高胆固醇血症对照组明显升高 (P <0 .0 1和P <0 .0 5 )。高胆固醇血症对照组大鼠血清及肝匀浆MDA含量与正常对照组比较明显升高。与高胆固醇血症对照组比较 ,大豆异黄酮 30和 6 0mg·kg- 1组大鼠血清MDA含量及 30和 12 0mg·kg- 1组大鼠肝脏MDA含量明显降低 (P <0 .0 5 )。结论 :对于高胆固醇血症大鼠红细胞及肝脏SOD活力的降低及血清和肝脏MDA水平的升高 ,能被大豆异黄酮部分逆转     

大豆异黄酮对初老大鼠卵巢Bcl-2基因和Caspase-3基因mRNA表达的影响

目的观察大豆异黄酮(soy isoflavones,SI)对初老大鼠卵巢Bcl-2、Caspas e-3 mRNA表达及氧自由基含量的影响。方法利用自然衰老的雌性大鼠建立初老动物模型,连续灌胃给药8周后,采用逆转录-聚合酶链反应(RT-PCR)检测卵巢Bcl-2和Caspase-3 mRNA表达,采用硫代巴比妥酸和黄嘌呤氧化法分别检测卵巢丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果与初老组相比,各SI处理组卵巢Bcl-2 mRNA表达量和SOD的活性均明显增高、Caspase-3表达量明显下降,中剂量(158 mg.kg-1)和高剂量(500 mg.kg-1)SI处理组MDA含量也显著降低(P<0.05或P<0.01)。结论大豆异黄酮上调卵巢Bcl-2、下调Caspase-3表达、抑制氧自由基生成并增强SOD活性,可能是其改善衰老卵巢功能的机制之一。     

大豆异黄酮预防离体大鼠心肌缺血再灌注损伤

目的:观察大豆异黄酮(SI)预处理对离体大鼠心肌缺血再灌注损伤的影响。方法:应用Langendorff灌注大鼠离体心脏,停灌/复灌方式制备缺血再灌注模型。SD雄性大鼠40只,随机分为正常对照组、缺血再灌注组(I/R)、低剂量SI组(L-SI)、中剂量SI组(M-SI)、高剂量SI组(H-SI),L-SI、M-SI、H-SI组分别予SI 30、60、120mg.kg-1.d-1灌胃,第15天末采集心脏收缩期左心室内压上升的最大变化速率(+LVdp/dtmax)、舒张期左心室内压下降的最大变化速率(-LVdp/dtmax)及左室发展压(LVDP)、左心室舒张末压(LVEDP)及心率与发展压的乘积(RPP)并分析;电镜观察心肌细胞超微结构改变。结果:与正常对照组比较,I/R组LVEDP明显升高(P<0.01);LVDP,+dp/dtmax,-dp/dtmax,RPP均明显降低(P<0.05,P<0.01)。与I/R组比较,M-SI组LVEDP明显降低(P<0.01),RPP明显升高(P<0.05)。与I/R组比较,H-SI组LVDP、+dp/dtmax、-dp/dtmax均明显升高(P<0.05,P<0.01)。I/R组中,心肌纤维断裂,线粒体肿胀,嵴破坏消失,此变化在M-SI、H-SI预处理组中明显减轻。结论:中、高剂量SI对离体缺血再灌注大鼠受损伤的心肌有保护作用。