Science.gov

Sample records for phytoestrogens stimulate spermatogenic

  1. Modulation of Aromatase by Phytoestrogens

    PubMed Central

    Lephart, Edwin D.

    2015-01-01

    The aromatase enzyme catalyzes the conversion of androgens to estrogens in many human tissues. Estrogens are known to stimulate cellular proliferation associated with certain cancers and protect against adverse symptoms during the peri- and postmenopausal intervals. Phytoestrogens are a group of plant derived naturally occurring compounds that have chemical structures similar to estrogen. Since phytoestrogens are known to be constituents of animal/human food sources, these compounds have received increased research attention. Phytoestrogens may contribute to decreased cancer risk by the inhibition of aromatase enzyme activity and CYP19 gene expression in human tissues. This review covers (a) the aromatase enzyme (historical descriptions on function, activity, and gene characteristics), (b) phytoestrogens in their classifications and applications to human health, and (c) a chronological coverage of aromatase activity modulated by phytoestrogens from the early 1980s to 2015. In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the aromatase enzyme itself, or (c) in some cases acting at both levels of regulation. The findings presented herein are consistent with estrogen's impact on health and phytoestrogen's potential as anticancer treatments, but well-controlled, large-scale studies are warranted to determine the effectiveness of phytoestrogens on breast cancer and age-related diseases. PMID:26798508

  2. Phytoestrogens and their effects.

    PubMed

    Sirotkin, Alexander V; Harrath, Abdel Halim

    2014-10-15

    The chemical structure, classification, source, metabolism, physiological and health effects of plant phytoestrogens and mechanisms of their action are reviewed. The available knowledge suggests that phytoestrogens can affect a number of physiological and pathological processes related to reproduction, bone remodeling, skin, cardiovascular, nervous, immune systems and metabolism. Due to these effects, phytoestrogens and phytoestrogen-containing diet can be useful for the prevention and treatment of menopausal symptoms, skin aging, osteoporosis, cancer, cardiovascular, neurodegenerative, immune and metabolic diseases. Possible problems in understanding and application of phytoestrogens (multiple targets and multiple estrogen receptor -dependent and -independent mechanisms of action, the discrepancy between the results of experimental and clinical studies, adequate source of phytoestrogen) have been discussed.

  3. Pharmaceutical prospects of phytoestrogens.

    PubMed

    Usui, Takeshi

    2006-02-01

    Interest in the physiologic and pharmacologic role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the classes of compounds known as the phytoestrogens, which embody several groups of non-steroidal estrogens, including isoflavones and lignans that are widely distributed within nature. The impact of dietary phytoestrogens on normal biologic processes was first recognized in sheep. Observations of sheep grazing on fields rich in clover and cheetahs fed high soy diets in zoos suggested that flavonoids and related phytochemicals can affect mammalian health. Endogenous estrogens have an important role not only in the hypothalamic-pituitary-gonadal axis, but also in various non-gonadal systems, such as cardiovascular systems, bone, and central nervous systems, and lipid metabolism. There have been several clinical studies of hormone replacement therapy (HRT) in post-menopausal women to examine whether HRT has beneficial effects on the cardiovascular system, bone fractures, lipid metabolism, and Alzheimer's disease. In addition, estrogen contributes to the development of some estrogen-dependent cancers, such as breast cancer and prostate cancer and the number of patients with these cancers is increasing in developed countries. Although recent mega-studies showed negative results for classical HRT in the prevention of some of these diseases, the molecules that interact with estrogen receptors are candidate drugs for various diseases, including hormone-dependent cancers. This review focuses on the molecular properties and pharmaceutical potential of phytoestrogens.

  4. Phytoestrogens and bone.

    PubMed

    Anderson, J J; Garner, S C

    1998-12-01

    Practically all plant foods contain small amounts of the diverse phytoestrogen molecules that have the potential to improve health. Phytoestrogens, especially the soy-derived isoflavones, are receiving great scrutiny as food supplements for the purposes of both enhancing the health of tissues and preventing several common diseases, such as cardiovascular diseases, cancers of reproductive tissues and osteoporosis. Investigations of isoflavones, in particular, have recently become more prominent because of their oestrogenic activities. These actions may be as either partial oestrogen agonists or anti-oestrogens (inhibitors of natural oestrogen activity). For example, the isoflavones of soy, mainly genistein and daidzein, have been shown by at least three different laboratories to conserve bone in ovariectomized rodent models, and they probably have similar conservatory effects in higher mammalian species. Nevertheless, the only positive effects of phytoestrogens on bone observed so far in post-menopausal women have been small and limited to the lumbar vertebrae. Additional information on human studies currently in progress is needed before the efficacy of these preparations in human subjects is known.

  5. Genotoxicity of phytoestrogens.

    PubMed

    Stopper, H; Schmitt, E; Kobras, K

    2005-07-01

    Plant extracts containing phytohormones are very popular as 'alternative' medicine for many kinds of diseases. They are especially favored by women who enter menopause and are concerned about the side effects of hormone replacement therapy. However, adverse health effects of phytoestrogens have often been ignored. This review examines the literature on genotoxicity and apoptotic effects of phytohormones. Genistein, coumestrol, quercetin, zearalenone, and resveratrol exerted genotoxic effects in in vitro test systems. Other phytoestrogens such as lignans, the isoflavones daidzein and glycetein, anthocyanidins, and the flavonol fisetin exhibited only weak or no effects in vitro. However, some metabolites of daidzein showed a genotoxic activity in vitro. Practically all of the phytoestrogens exhibit pro-apoptotic effects in some cell systems. Further investigations regarding dose-response-relationships and other aspects relevant for extrapolation to human exposure seem necessary. Until then, care may be advised in taking concentrated phytohormones. Nevertheless, the intake of substantial amounts of plant-food in a normal diet constitutes an important, individual contribution to cancer prevention.

  6. Phytoestrogens and the metabolic syndrome.

    PubMed

    Jungbauer, Alois; Medjakovic, Svjetlana

    2014-01-01

    Phytoestrogens are a diverse class of non-steroidal compounds that have an affinity for estrogen receptors α and β, for the peroxisome proliferator-activated receptor (PPAR) family and for the aryl hydrocarbon receptor. Examples of phytoestrogens include prenylated flavonoids, isoflavones, coumestans and lignans. Many phytoestrogens counteract the cellular derailments that are responsible for the development of metabolic syndrome. Here we propose a mechanism of action which is based on five pillars/principles. First, phytoestrogens are involved in the downregulation of pro-inflammatory cytokines, such as COX-2 and iNOS, by activating PPAR and by inhibiting IκB activation. Second, they increase reverse cholesterol transport, which is mediated by PPARγ. Third, phytoestrogens increase insulin sensitivity, which is mediated via PPARα. Fourth, they exert antioxidant effects by activating antioxidant genes through KEAP. Fifth, phytoestrogens increase energy expenditure by affecting AMP-activated kinase signaling cascades, which are responsible for the inhibition of adipogenesis. In addition to these effects, which have been demonstrated in vivo and in clinical trials, other effects, such as eNOS activation, may also be important. Some plant extracts from soy, red clover or licorice can be described as panPPAR activators. Fetal programming for metabolic syndrome has been hypothesized; thus, the consumption of dietary phytoestrogens during pregnancy may be relevant. Extracts from soy, red clover or licorice oil have potential as plant-derived medicines that could be used to treat polycystic ovary syndrome, a disease linked to hyperandrogenism and obesity, although clinical trials have not yet been conducted. Phytoestrogens may help prevent metabolic syndrome, although intervention studies will be always be ambiguous, because physical activity and reduced calorie consumption also have a significant impact. Nevertheless, extracts rich in phytoestrogens may be an

  7. [Phytoestrogens and menopause].

    PubMed

    Torella, M; La Rezza, F; Labriola, D; Ammaturo, F P; Ambrosio, D; Zarcone, R; Trotta, C; Schettino, M T; De Franciscis, P

    2013-12-01

    Menopause is the interruption of menstrual and reproductive capacity, therefore, that occurs naturally in all women between 48 and 55 years, due to a lower production of gonadal steroids. The period becomes progressively irregular and lack of ovulation and menstrual flow decrease, and finally disappears. The time between the first symptoms and the cessation of the menstrual cycle is called menopause. With the onset of menopause the woman undergoes a series of changes related to estrogen deficiency, which occur in all tissues of the body. In this period one can distinguish an early stage, characterized by hot flashes, mood swings, night sweats and insomnia, and a late phase in which we highlight more symptoms related to the interruption of hormonal such as osteoporosis, obesity, at urogenital and increased incidence of cardiovascular disease. In Italy, only 5.2% of women aged 45-64 years used hormone replacement therapy, and only 20-30% follow a therapy for more than two years, both for psychological reasons, and for fear of side effects. Not surprisingly, therefore, phytoestrogens are given a high importance, as they are considered a natural alternative tank to to their plant origin. Interest in phytoestrogens was born from the observation that postmenopausal women who live in the East have a lower incidence of symptoms, cardiovascular disease, cancer and osteoporosis hormone use, compared to Western women.

  8. A Commentary on Phytoestrogens and Disease

    ERIC Educational Resources Information Center

    Hard, Alison; Edelstein, Sari

    2015-01-01

    On the most basic level, phytoestrogens can be defined as compounds found in plants that exhibit estrogen-like activity in the human body. Phytoestrogens are considered functional foods because of their diverse physiological effects beyond basic nutritional functions. The 2 primary categories of phytoestrogens found in food are lignans and…

  9. Phytoestrogens and post reproductive health.

    PubMed

    Baber, Rod

    2010-08-01

    The use of phytoestrogens for various perceived health benefits is widespread. Despite 20 years of research the evidence for any significant health benefits remains inconclusive. Pre clinical trials have demonstrated both non-genomic and genomic actions of constituents of phytoestrogens including selective, but weak, binding to estrogen receptors, with a preference for ER B over ER A. Evidence of clinically relevant biological effects from observational studies and randomized trials has, in general, been lacking. Despite many trials there remains little evidence that phytoestrogens, whether dietary or supplemented, significantly relieve menopausal vasomotor symptoms or cognition. Several potential mechanisms for a positive effect on bone and cardiovascular health have been demonstrated however no fracture prevention data or cardiovascular end point benefit has yet been demonstrated. In vitro effects of phytoestrogens on breast cells have been both stimulatory and inhibitory however net effects appear neutral with observational studies finding no change in breast cancer risk. No effect has been seen on endometrial or other cancers and side effect profiles have, in general, been mild.

  10. Erythroidine alkaloids: a novel class of phytoestrogens.

    PubMed

    Djiogue, Sefirin; Halabalaki, Maria; Njamen, Dieudonné; Kretzschmar, Georg; Lambrinidis, George; Hoepping, Josephine; Raffaelli, Francesca M; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Vollmer, Günter

    2014-07-01

    Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only β-erythroidine bound to ERβ (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of

  11. Effectiveness of phytoestrogens in climacteric medicine.

    PubMed

    Al-Azzawi, Farook; Wahab, May

    2010-09-01

    The increased interest in phytoestrogens in the management of menopausal symptoms followed the publication of the Women's Health Initiative study. A wide-spread perception that these plant-derived compounds are equivalent to estrogen was established. These compounds evolved to fulfill the needs of plant physiological processes and are natural for the plant cells but not natural to the human cell. Epidemiological data suggest a possible protective effect of phytoestrogen if consumed during adolescence, but later on in life this effect is not clear. The utility of phytoestrogen as a "natural and safe" alternative to estrogen in alleviating vasomotor symptoms has failed the test in randomized clinical trials. Because many breast cancer sufferers seek in phytoestrogen a relief of estrogen deficiency symptoms, the possible interaction of such remedies with risk of recurrence of breast cancer or interference with tamoxifen action should not be overlooked.

  12. Soy and phytoestrogens: possible side effects.

    PubMed

    Jargin, Sergei V

    2014-01-01

    Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

  13. The pros and cons of phytoestrogens

    PubMed Central

    Patisaul, Heather B.; Jefferson, Wendy

    2011-01-01

    Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens. PMID:20347861

  14. The pros and cons of phytoestrogens.

    PubMed

    Patisaul, Heather B; Jefferson, Wendy

    2010-10-01

    Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens.

  15. Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice

    PubMed Central

    Sato, Takuya; Yokonishi, Tetsuhiro; Komeya, Mitsuru; Katagiri, Kumiko; Kubota, Yoshinobu; Matoba, Shogo; Ogonuki, Narumi; Ogura, Atsuo; Yoshida, Shosei; Ogawa, Takehiko

    2012-01-01

    Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, we show that one of the most severe types of spermatogenic defect mutant can be treated by the culture method without any genetic manipulations. The Sl/Sld mouse is used as a model of such male infertility. The testis of the Sl/Sld mouse has only primitive spermatogonia as germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the surface of Sertoli cells. To compensate for the deficit, we cultured testis tissues of Sl/Sld mice with a medium containing recombinant KITL and found that it induced the differentiation of spermatogonia up to the end of meiosis. We further discovered that colony stimulating factor-1 (CSF-1) enhances the effect of KITL and promotes spermatogenesis up to the production of sperm. Microinsemination of haploid cells resulted in delivery of healthy offspring. This study demonstrated that spermatogenic impairments can be treated in vitro with the supplementation of certain factors or substances that are insufficient in the original testes. PMID:22984182

  16. Relationships between urinary biomarkers of phytoestrogens, phthalates, phenols, and pubertal stages in girls.

    PubMed

    Chakraborty, Tandra R; Alicea, Eilliut; Chakraborty, Sanjoy

    2012-01-01

    Phytoestrogens, phthalates, and phenols are estrogen-disrupting chemicals that have a pronounced effect at puberty. They are exogenous chemicals that are either plant-derived or man-made, and can alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding, or cellular responses of natural estrogens. Phytoestrogens, phthalates, and phenols are some of the potent estrogens detectable in urine. Phytoestrogens are plant-derived xenestrogens found in a wide variety of food products, like soy-based food, beverages, several fruits, and vegetables. Exposure to phytoestrogens can delay breast development and further lead to precocious puberty. The effect of phytoestrogens is mediated through estrogen receptors α and β or by binding with early immediate genes, such as jun and fos. Phthalates are multifunctional synthetic chemicals used in plastics, polyvinyl chloride products, cosmetics, hair spray, and children's toys. Phthalates have been shown to cause defeminization, thelarche, precocious puberty, and an increase in breast and pubic hair in pubertal girls. However, reports are also available that show no association of phthalates with precocious puberty in girls. Phthalates can act through a receptor-mediated signaling pathway or affect the production of luteinizing hormone and follicle-stimulating hormone that has a direct effect on estrogen formation. Phenols like bisphenol A are industrial chemicals used mainly in the manufacture of polycarbonates and plastic materials. Bisphenol A has been shown to cause precocious puberty and earlier menarche in pubertal girls. Reports suggest that the neurotoxic effect of bisphenol A can be mediated either by competing with estradiol for binding with estrogen receptors or via the ERK/NK-kappa or ERRγ pathway. This review demonstrates the effects of phytoestrogens, phthalates, and phenols on the development of girls during puberty.

  17. Environmental Epigenetics and Phytoestrogen/Phytochemical Exposures

    PubMed Central

    Guerrero-Bosagna, Carlos M.; Skinner, Michael K.

    2013-01-01

    One of the most important environmental factors to promote epigenetic alterations in an individual is nutrition and exposure to plant compounds. Phytoestrogens and other phytochemicals have dramatic effects on cellular signaling events, so have the capacity to dramatically alter developmental and physiological events. Epigenetics provides one of the more critical molecular mechanisms for environmental factors such as phytoestrogens/phytochemicals to influence biology. In the event these epigenetic mechanisms become heritable through epigenetic transgenerational mechanisms the impacts on the health of future generations and areas such as evolutionary biology need to be considered. The current review focuses on available information on the environmental epigenetics of phytoestrogen/phytochemical exposures, with impacts on health, disease and evolutionary biology considered. PMID:23274117

  18. Phytoestrogens and cognitive function: a review.

    PubMed

    Soni, Mira; Rahardjo, Tri Budi W; Soekardi, Rodiyah; Sulistyowati, Yenny; Lestariningsih; Yesufu-Udechuku, Amina; Irsan, Atik; Hogervorst, Eef

    2014-03-01

    Neuroprotective effects of phytoestrogen compounds (found in soy) have been demonstrated in animal research and cell culture studies. In particular, phytoestrogens have been shown to reduce Alzheimer's Disease (AD) related pathology, potentially alleviating risk of AD progression. In addition to their antioxidant properties, soy products also have the ability to affect cognition via interaction with estrogen receptors. However, observational studies and randomised controlled trials in humans have resulted in inconclusive findings within this domain. There are several possible reasons for these discrepant data. Studies which report no effect of phytoestrogens on cognition have mainly been carried out in European cohorts, with an average low dietary consumption. In contrast, investigation of Asian populations, with a higher general intake of tofu (a non-fermented soy product) have shown negative associations with cognitive function in those over the age of 65. Consideration of type of soy product is important, as in the latter sample, protective effects of tempe (fermented soy) were also observed. Limited data provide evidence that effects of phytoestrogens on cognition may be modified by dosage, duration of consumption and cognitive test used. Additionally, characteristics of the study population including age, gender, ethnicity and menopausal status appear to be mediating variables. Phytoestrogen treatment interventions have also shown time-limited positive effects on cognition. These findings are consistent with estrogen treatment studies, where initial positive short-term cognitive effects may occur, which reverse with long-term continuous use in elderly women. Well controlled, large scale studies are needed to assess the effects of phytoestrogens on the aging brain and provide further understanding of this association.

  19. Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.

    PubMed

    Albini, A; Rosano, C; Angelini, G; Amaro, A; Esposito, A I; Maramotti, S; Noonan, D M; Pfeffer, U

    2014-01-01

    Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ERα and ERβ and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).

  20. Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

    PubMed Central

    Albini, A.; Rosano, C.; Angelini, G.; Amaro, A.; Esposito, A.I.; Maramotti, S.; Noonan, D.M.; Pfeffer, U.

    2014-01-01

    Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ERα and ERβ and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto- and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs). PMID:24304271

  1. Activation of southern white rhinoceros (Ceratotherium simum simum) estrogen receptors by phytoestrogens: potential role in the reproductive failure of captive-born females?

    PubMed

    Tubbs, Christopher; Hartig, Phillip; Cardon, Mary; Varga, Nicole; Milnes, Matthew

    2012-03-01

    The captive southern white rhinoceros (SWR; Ceratotherium simum simum) population serves as an important genetic reservoir critical to the conservation of this vulnerable species. Unfortunately, captive populations are declining due to the poor reproductive success of captive-born females. Captive female SWR exhibit reproductive problems suggested to result from continual ovarian follicular activity and prolonged exposure to endogenous estrogen. However, we investigated the potential role of exogenous dietary phytoestrogens in the reproductive failure of SWR by cloning and characterizing in vitro phytoestrogen binding and activation of recombinant SWR estrogen receptors (ESR). We compared those characteristics with recombinant greater one-horned rhinoceros (GOHR; Rhinoceros unicornis) ESR, a species that receives similar captive diets yet reproduces relatively well. Our results indicate that phytoestrogens bind rhino ESR in a manner similar to other vertebrate species, but there are no differences found in phytoestrogen binding affinity of SWR ESR compared with GOHR ESR. However, species-specific differences in ESR activation by phytoestrogens were detected. The phytoestrogen coumestrol stimulated greater maximal activation of SWR ESR1 than GOHR ESR1. SWR ESR2 were also more sensitive to phytoestrogens and were activated to a greater extent by both coumestrol and daidzein. The concentrations in which significant differences in ESR activation occurred (10(-7) to 10(-5) m) are consistent with circulating concentrations measured in other vertebrate species. Taken together, these findings suggest that phytoestrogens potentially pose a risk to the reproductive health of captive SWR. However, additional studies are needed to further clarify the physiological role of dietary phytoestrogens in the reduced fertility of this species.

  2. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-08-09

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

  3. Bioactivation of Phytoestrogens: Intestinal Bacteria and Health.

    PubMed

    Landete, J M; Arqués, J; Medina, M; Gaya, P; de Las Rivas, B; Muñoz, R

    2016-08-17

    Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

  4. Hypospadias and maternal intake of phytoestrogens.

    PubMed

    Carmichael, Suzan L; Cogswell, Mary E; Ma, Chen; Gonzalez-Feliciano, Amparo; Olney, Richard S; Correa, Adolfo; Shaw, Gary M

    2013-08-01

    Experimental data indicate that gestational exposures to estrogenic compounds impact risk of hypospadias. We examined whether risk of hypospadias (i.e., a congenital malformation in which the opening of the penile urethra occurs on the ventral side of the penis) was associated with maternal intake of phytoestrogens, given their potential impact on estrogen metabolism. The analysis included data on mothers of 1,250 hypospadias cases and 3,118 controls who delivered their infants from 1997 to 2005 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. After adjustment for several covariates, high intakes of daidzein, genistein, glycetin, secoisolariciresinol, total isoflavones, total lignans, and total phytoestrogens were associated with reduced risks; odds ratios comparing intakes ≥90th percentile with intakes between the 11th and 89th percentiles ranged from 0.6 to 0.8. For example, the odds ratio for total phytoestrogen intake was 0.7 (95% confidence interval: 0.5, 1.0). This study represents the first large-scale analysis of phytoestrogen intake and hypospadias. The observed associations merit investigation in additional populations before firm conclusions can be reached.

  5. Spermatogenic cycle of a plethodontid salamander, Eurycea longicauda (Amphibia, Urodela)

    PubMed Central

    Siegel, Dustin S; Alvino, Sam; Trauth, Stanley E; Sever, David M; Gribbins, Kevin M

    2014-01-01

    Previous investigators have described the spermatogenic cycles of numerous species of plethodontid salamanders. Most studies describe a fairly stereotypical cycle with meiotic divisions of spermatogenesis commencing in the spring/summer. However, many studies lack details obtainable from histological examination and/or testicular squashes and, instead, provide only mensural data from the testes. Studies that lacked microscopic evaluation often revealed spermatogenic cycles that varied greatly from that of the stereotypical cycle with meiotic divisions commencing in the fall/winter. Those studies hamper comparisons between the spermatogenic cycles of different species and their environments, as they do not provide a correlation between testicular size and any aspect of the spermatogenic cycle. In the following manuscript, we elucidate the spermatogenic cycle of Eurycea longicauda longicauda in an effort to outline an appropriate protocol for analyzing spermatogenesis in salamanders that will facilitate future comparative studies. Like many Nearctic plethodontids, E. l. longicauda exhibits a meiotic wave that travels through the testes during the summer; this process is followed by spermiogenesis, spermiation, and recrudescence in the fall, winter, and spring. PMID:26413402

  6. Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer.

    PubMed

    Kumar, Rajeev; Verma, Vikas; Jain, Ashish; Jain, Rajeev K; Maikhuri, Jagdamba P; Gupta, Gopal

    2011-08-01

    Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 μM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 μM of G, B or Q or 12.5+12.5 μM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 μM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-β, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo.

  7. Behavioral changes in fish exposed to phytoestrogens.

    PubMed

    Clotfelter, Ethan D; Rodriguez, Alison C

    2006-12-01

    We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, beta-sitosterol, and the positive control 17beta-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17beta-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes.

  8. Behavioral changes in fish exposed to phytoestrogens.

    PubMed

    Clotfelter, Ethan D; Rodriguez, Alison C

    2006-12-01

    We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, beta-sitosterol, and the positive control 17beta-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17beta-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes. PMID:16584819

  9. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  10. Gastroschisis and maternal intake of phytoestrogens.

    PubMed

    Wadhwa, Elizabeth L; Ma, Chen; Shaw, Gary M; Carmichael, Suzan L

    2016-08-01

    The prevalence of gastroschisis has increased significantly in the past few decades. The strongest risks have been observed for women <25 years old or of low body mass index, and maternal diet also been proposed to be associated with risk. The objective of this study was to evaluate whether the risk of gastroschisis is associated with maternal dietary intake of phytoestrogens. The analysis includes data on mothers of 409 gastroschisis cases and 3,007 controls who delivered their infants from 2005 to 2010 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. Detailed information was obtained from maternal telephone interviews that included a validated food frequency questionnaire. We conducted logistic regression analyses that included each phytoestrogen in its continuous form (to test for linearity) and quadratic form (to test for non-linearity), adjusted for maternal energy intake, age, BMI, race-ethnicity, and smoking in 1st trimester. Logistic regression analysis indicated that biochanin A, formonoetin, and coumestrol had a significant non-linear association with gastroschisis (P-value <0.05 for quadratic term). Lower intakes were associated with increased risk, with somewhat stronger but relatively modest associations at the lower end of the distribution; for example, the ORs for the 10th versus 50th percentiles ranged from 1.1 to 1.2. Associations were not significant for the other phytoestrogens. This study provides some evidence for association with certain phytoestrogens, after adjusting for covariates. The implications of our findings for clinical practice are uncertain pending other studies examining this association. © 2016 Wiley Periodicals, Inc. PMID:27232448

  11. Butylbenzyl phthalate induces spermatogenic cell apoptosis in prepubertal rats.

    PubMed

    Alam, Mohammad Shah; Kurohmaru, Masamichi

    2016-02-01

    Butylbenzyl phthalate (BBP), a suspected endocrine disruptor, adversely affects male reproductive function. In this study, morphological alterations of prepubertal rat testes caused by single administration of BBP, were examined by light microscopy. Three-week-old male rats were given a single dose of 500 mg/kg BBP by oral gavage and sacrificed at 3, 12, and 24 h after administration. Histopathological examination revealed progressive detachment and sloughing of spermatogenic cells into the lumen, and a significant increase in the number of TUNEL-positive (apoptotic) spermatogenic cells in the treated groups, compared to the control. Semithin sections confirmed the apoptotic cells by their prominent basophilia, condensed chromatin, and shrunken cytoplasm, hallmarks of apoptotic cell death. Immunohistochemistry identified disruption of Sertoli cell vimentin and actin filaments in the treated groups. To elucidate the recovery effects of BBP, rats were treated in the same way and were sacrificed at D1-12h after administration. The apoptotic index returned to normal at D9. While, the testes revealed lower weight gain until D12. These results show for the first time that BBP induces collapse of vimentin filaments in Sertoli cells which may lead to disruption of Sertoli-spermatogenic cell physical interaction and induces spermatogenic cell apoptosis. PMID:26747412

  12. Anticarcinogenic Effects of Dietary Phytoestrogens and Their Chemopreventive Mechanisms.

    PubMed

    Hwang, Kyung-A; Choi, Kyung-Chul

    2015-01-01

    Phytoestrogens are phenolic compounds derived from plants and exert an estrogenic as well as an antiestrogenic effect and also various biological efficacies. Chemopreventive properties of phytoestrogens has emerged from epidemiological observations indicating that the incidence of some cancers including breast and prostate cancers is much lower in Asian people, who consume significantly higher amounts of phytoestrogens than Western people. There are 4 main classes of phytoestrogens: isoflavones, stilbenes, coumestans, and lignans. Currently, resveratrol is recognized as another major phytoestrogen present in grape and red wine and has been studied in many biological studies. Phytoestrogens have biologically diverse profitabilities and advantages such as low cytotoxicity to patients, lack of side effects in clinical trials, and pronounced benefits in a combined therapy. In this review, we highlighted the effects of genistein, daidzein, and resveratrol in relation with their anticarcinogenic activity. A lot of in vitro and in vivo results on their chemopreventive properties were presented along with the underlying mechanisms. Besides well-known mechanisms such as antioxidant property and apoptosis, newly elucidated anticarcinogenic modes of action including epigenetic modifications and topoisomerase inhibition have been provided to examine the possibility of phytoestrogens as promising reagents for cancer chemoprevention and/or treatment and to suggest the importance of plant-based diet of phytoestrogens.

  13. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

  14. Phytoestrogens and avian reproduction: Exploring the evolution and function of phytoestrogens and possible role of plant compounds in the breeding ecology of wild birds.

    PubMed

    Rochester, Johanna R; Millam, James R

    2009-11-01

    Phytoestrogens are secondary plant compounds, which can act to mimic estrogen and cause the disruption of estrogenic responses in organisms. Although there is a substantial body of research studying phytoestrogens, including their mechanisms of estrogenic effects, evolution, and detection in biological systems, little is known about their ecological significance. There is evidence, however, that an ecological relationship involving phytoestrogens exists between plants and animals-plants may produce phytoestrogens to reduce fecundity of organisms that eat them. Birds and other vertebrates may also exploit phytoestrogens to regulate their own reproduction-there are well known examples of phytoestrogens inhibiting reproduction in higher vertebrates, including birds. Also, common plant stressors (e.g., high temperature) increase the production of secondary plant compounds, and, as evidence suggests, also induce phytoestrogen biosynthesis. These observations are consistent with the single study ever done on phytoestrogens and reproduction in wild birds [Leopold, A.S., Erwin, M., Oh, J., Browning, B., 1976. Phytoestrogens adverse effects on reproduction in California quail. Science 191, 98-100.], which found that drought stress correlated with increased levels of phytoestrogens in plants, and that increased phytoestrogen levels correlated with decreased young. This review discusses the hypothesis that plants may have an effect on the reproduction of avian species by producing phytoestrogens as a plant defense against herbivory, and that birds may "use" changing levels of phytoestrogens in the vegetation to ensure that food resources will support potential young produced. Evidence from our laboratory and others appear to support this hypothesis.

  15. Stimulants

    MedlinePlus

    Stimulants are drugs that increase your heart rate, breathing rate, and brain function. Some stimulants affect only a specific organ, such as the heart, lungs, brain, or nervous system. Epinephrine is a stimulant. It ...

  16. Dietary Phytoestrogen Intakes and Cognitive Function During the Menopause Transition: Results from the SWAN Phytoestrogen Study

    PubMed Central

    Greendale, Gail A.; Huang, Mei-Hua; Leung, Katherine; Crawford, Sybil L.; Gold, Ellen B.; Wight, Richard; Waetjen, Elaine; Karlamangla, Arun S.

    2011-01-01

    Objective Phytoestrogens, which consist mainly of isoflavones, lignans and coumestans have estrogenic and anti-inflammatory properties. Prior research suggests that higher dietary or supplemental intakes of isoflavones and lignans are related to better cognitive performance in middle aged and older women. Methods We conducted longitudinal analysis of dietary phytoestrogens and cognitive performance in a cohort of African-American, white, Chinese and Japanese women undergoing the menopause transition (MT). Tests were: Symbol Digit Modalities, East Boston Memory and Digits Span Backward. Phytoestrogens were assessed by Food Frequency Questionnaire. We modeled each cognitive score as a function of concurrent value of the primary predictors (highest tertile of isoflavones, lignans or coumestrol) and covariates including MT stage. Results Coumestrol and isoflavone intakes were 10 and 25 times greater, respectively, in Asian versus non-Asian participants. During late perimenopause and postmenopause, Asian women with high isoflavone intakes did better on processing speed, but during early perimenopause and postmenopause, high isoflavone Asian consumers performed worse on verbal memory. The highest isoflavone consumers among non-Asians likewise posted lower verbal memory scores during early perimenopause. A verbal memory benefit of higher dietary lignan consumption was apparent only during late perimenopause, when women from all ethnic/racial groups who were in the highest tertile of intake demonstrated a small advantage. Coumestrol was unrelated to cognitive performance. Conclusions Cognitive effects of dietary phytoestrogens are small, appear to be class-specific, vary by menopause stage and cognitive domain and differ among ethic/racial groups (but whether this is related to dose or to host factors cannot be discerned). PMID:22415567

  17. Developing phytoestrogens for breast cancer prevention.

    PubMed

    Liu, Mandy M; Huang, Ying; Wang, Jeffrey

    2012-12-01

    Breast cancer is one of the most common types of cancer in women, and is the second leading cause of cancer-related deaths in the United States. Chemoprevention using phytoestrogens (PEs) for breast cancer may be a valid strategy. PEs are phytochemicals with estrogen-like structures and can be classified into four types: isoflavones, lignans, stilbenes and coumestans. They are widely distributed in diet and herbs and have shown anti-cancer activity via mechanisms including estrogen receptor modulation, aromatase inhibition, and anti-angiogenesis. Genistein, daidzein and resveratrol are some of the most studied PE examples. Quality control in product manufacturing and clinical study design is a critical issue in developing them as clinically effective chemopreventive agents for breast cancer.

  18. Phytoestrogens and human health effects: weighing up the current evidence.

    PubMed

    Humfrey, C D

    1998-01-01

    Phytoestrogens are naturally occurring plant compounds which have oestrogenic and/or anti-oestrogenic activity. They are present in many human foodstuffs including beans, sprouts, cabbage, spinach, soyabean, grains and hops. The main classes are the isoflavones, coumestans and lignans. This review assesses the evidence that these substances may have adverse and/or beneficial impacts on the risk of several hormone-dependent diseases in humans. Evidence from studies of various animal species has demonstrated that ingestion of high levels of phytoestrogens can produce adverse effects on reproductive endpoints including fertility. Studies in laboratory animals have also shown that exposure to high doses of phytoestrogens during development can adversely affect brain differentiation and reproductive development in rodents, but may also have possible beneficial effects. In humans, there is a lack of information concerning the possible effects of high doses of phytoestrogens in infants and this should be addressed as a matter of priority so that any risks (or benefits) can be established. In adults, no current data exist to suggest that consumption of phytoestrogens at the levels normally encountered in the diet is likely to be harmful. Epidemiological studies suggest that foodstuffs containing phytoestrogens may have a beneficial role in protecting against a number of chronic diseases and conditions. For cancer of the prostate, colon, rectum, stomach and lung, the evidence is most consistent for a protective effect resulting from a high intake of grains, legumes, fruits and vegetables; it is not possible to identify particular food types or components that may be responsible. Dietary intervention studies indicate that in women soya and linseed may have beneficial effects on the risk of breast cancer and may help to alleviate postmenopausal symptoms. For osteoporosis, tentative evidence suggests phytoestrogens may have similar effects in maintaining bone density to those

  19. Effects of phytoestrogens on expression of genes regulating growth-related processes in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytoestrogens are plant-derived isoflavones that activate estrogen receptors. Phytoestrogen content of aquafeeds is increasing due to higher inclusion levels of soy and other legumes rich in these compounds. It is unknown whether phytoestrogens affect growth-related processes in a manner similar...

  20. Profiles of phytoestrogens in human urine from several Asian countries.

    PubMed

    Kunisue, Tatsuya; Tanabe, Shinsuke; Isobe, Tomohiko; Aldous, Kenneth M; Kannan, Kurunthachalam

    2010-09-01

    Intake of a diet rich in phytoestrogens has been associated with a decreased risk for hormone-dependent cancers in humans. Biomonitoring of phytoestrogens in human urine has been used to assess the intake of phytoestrogens. Although studies have reported phytoestrogen levels in urine specimens from the United States and Japan, little is known of human intake of phytoestrogens in other Asian countries. In this study we determined the concentrations of seven phytoestrogens, namely, enterolactone, enterodiol, daidzein, equol, O-desmethylangolensin (O-DMA), genistein, and coumestrol, in 199 human urine samples from three Asian countries, Vietnam (Hanoi and Ho Chi Minh), Cambodia (Phnom Penh), and India (Chennai and Kolkata), using a simple, sensitive, and reliable liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method. The residue levels of phytoestrogens in urine samples from the three Asian countries were compared with the concentrations in 26 urine samples from Japan (Ehime) and 16 urine samples from the United States (Albany), analyzed in this study. Among the phytoestrogens analyzed, isoflavones such as daidzein and genistein were predominant in urine samples from Vietnam; samples from Cambodia and India contained higher concentrations of enterolactone than isoflavones. Urinary concentrations of isoflavones in samples from Hanoi, Vietnam, were notably higher than the concentrations in samples from Cambodia, India, and the United States and similar to the concentrations in samples from Japan. The lowest concentrations of daidzein and the highest concentrations of enterolactone were found in urine samples from India. Concentrations of equol and O-DMA, which are microbial transformation products of daidzein (produced by gut microflora), were notably high in urine samples from Hanoi, Vietnam. The ratios of the concentration of equol or O-DMA to that of daidzein were significantly higher in samples from Hanoi than from Japan, indicating high

  1. ALDH Enzyme Expression Is Independent of the Spermatogenic Cycle, and Their Inhibition Causes Misregulation of Murine Spermatogenic Processes.

    PubMed

    Kent, Travis; Arnold, Samuel L; Fasnacht, Rachael; Rowsey, Ross; Mitchell, Debra; Hogarth, Cathryn A; Isoherranen, Nina; Griswold, Michael D

    2016-01-01

    Perturbations in the vitamin A metabolism pathway could be a significant cause of male infertility, as well as a target toward the development of a male contraceptive, necessitating the need for a better understanding of how testicular retinoic acid (RA) concentrations are regulated. Quantitative analyses have recently demonstrated that RA is present in a pulsatile manner along testis tubules. However, it is unclear if the aldehyde dehydrogenase (ALDH) enzymes, which are responsible for RA synthesis, contribute to the regulation of these RA concentration gradients. Previous studies have alluded to fluctuations in ALDH enzymes across the spermatogenic cycle, but these inferences have been based primarily on qualitative transcript localization experiments. Here, we show via various quantitative methods that the three well-known ALDH enzymes (ALDH1A1, ALDH1A2, and ALDH1A3), and an ALDH enzyme previously unreported in the murine testis (ALDH8A1), are not expressed in a stage-specific manner in the adult testis, but do fluctuate throughout juvenile development in perfect agreement with the first appearance of each advancing germ cell type. We also show, via treatments with a known ALDH inhibitor, that lowered testicular RA levels result in an increase in blood-testis barrier permeability, meiotic recombination, and meiotic defects. Taken together, these data further our understanding of the complex regulatory actions of RA on various spermatogenic events and, in contrast with previous studies, also suggest that the ALDH enzymes are not responsible for regulating the recently measured RA pulse.

  2. Phytoestrogens in the environment, II: microbiological degradation of phytoestrogens and the response of fathead minnows to degradate exposure.

    PubMed

    Kelly, Megan M; Fleischhacker, Nathan T; Rearick, Daniel C; Arnold, William A; Schoenfuss, Heiko L; Novak, Paige J

    2014-03-01

    Phytoestrogens are endocrine active compounds derived from plants, including the isoflavones genistein and daidzein, and their methylated derivatives biochanin A and formononetin. These compounds have been detected at the µg/L level in the effluents of plant-processing industries and municipal treatment plants and at the ng/L level in surface waters worldwide. The present study assessed the persistence of genistein and daidzein in natural aquatic systems, specifically riverine samples. Initial concentration, temperature, sample location, and time of sample collection varied. Genistein and daidzein were found to be readily biodegradable at all tested concentrations, at both 10 °C and 20 °C, in samples collected during different seasons, and in samples from 3 different rivers. In addition, organismal responses in larval and sexually mature fathead minnows (Pimephales promelas) were quantified following exposure to microbiologically degraded phytoestrogens (genistein, daidzein, and formononetin). Products of the microbiological degradation of parent phytoestrogens did not affect larval survival, growth, or predator avoidance. Female adult fathead minnows exposed to these degradation products produced significantly fewer eggs than those exposed to a control, but no other morphological, physiological, or behavioral changes were observed with male or female minnows. The present research suggests that although phytoestrogens are not likely to persist in aquatic systems, they may pseudo-persist if discharges are continuous; in addition, caution should be exercised with respect to high-concentration effluents because of the potentially antiestrogenic effects of phytoestrogen degradates.

  3. Role of integrins, tetraspanins, and ADAM proteins during the development of apoptotic bodies by spermatogenic cells.

    PubMed

    Kierszenbaum, Abraham L; Rosselot, Carolina; Rivkin, Eugene; Tres, Laura L

    2006-07-01

    We have previously reported that Sertoli cell geometric changes induced by a Fas (CD95) agonist or by restricting Sertoli cell spreading can trigger spermatogenic cell detachment from Sertoli cell surfaces and initiate a programmed cell death sequence. Here, we have focused on ADAM proteins, tetraspanins CD9 and CD81, and the integrin beta1 subunit, which is co-expressed in testis with integrin alpha3 and integrin alpha6 subunits, to understand how these molecules may stabilize spermatogenic cell attachment to Sertoli cell surfaces. Like ADAM proteins, integrin beta1, alpha3, and alpha6 subunits, and CD9 and CD81 transcripts are expressed in the fetal testis and throughout testicular maturation, as well as, in Sertoli-spermatogenic cell co-cultures. Prespermatogonia (gonocytes) display CD9 and CD81 immunoreactive sites. Integrin alpha6 subunit transcripts have unusual developmental characteristics: fetal testis expresses the integrin alpha6B isoform exclusively. In contrast, the integrin alpha6B isoform co-exists with the integrin alpha6A isoform in prepubertal testes and Sertoli-spermatogenic cell co-cultures. A blocking anti body targeting the extracellular domain (N-terminal) of the integrin beta1 subunit causes rapid contraction of Sertoli cells leading to the gradual detachment of associated spermatogenic cells. In contrast, predicted active site peptides targeting the disintegrin domain of ADAM 1, ADAM 2, ADAM 3 (cyritestin), ADAM 4, ADAM 5, ADAM 6, and ADAM 15 (metragidin) do not disturb significantly the attachment of spermatogenic cells to Sertoli cell surfaces. Spermatogenic cells dislodged from their attachment sites by the integrin beta1 subunit blocking antibody display annexin V immunoreactivity, a sign of early apoptosis. Time-lapse videomicroscopy demonstrates that the removal by apoptosis of a single member of a spermatogenic cell cohort inter-connected by cytoplasmic bridges does not affect the remaining members of the cohort. During spermatogenic

  4. Cross-species and interassay comparisons of phytoestrogen action.

    PubMed

    Whitten, P L; Patisaul, H B

    2001-03-01

    This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

  5. Cross-species and interassay comparisons of phytoestrogen action.

    PubMed Central

    Whitten, P L; Patisaul, H B

    2001-01-01

    This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions. PMID:11250801

  6. Ameboid cells in spermatogenic cysts of caecilian testis.

    PubMed

    Smita, Mathew; Jancy, M George; Akbarsha, M A; Oommen, Oommen V

    2005-03-01

    Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule.

  7. Ameboid cells in spermatogenic cysts of caecilian testis.

    PubMed

    Smita, Mathew; Jancy, M George; Akbarsha, M A; Oommen, Oommen V

    2005-03-01

    Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule. PMID:15688448

  8. Effects of phytoestrogens and other plant-derived compounds on mesenchymal stem cells, bone maintenance and regeneration.

    PubMed

    Schilling, Tatjana; Ebert, Regina; Raaijmakers, Nadja; Schütze, Norbert; Jakob, Franz

    2014-01-01

    Phytoestrogens and other plant-derived compounds and extracts have been developed for the treatment of menopause-related complaints and disorders, e.g. hot flushes and osteoporosis. Since estrogens have been discussed to enhance the risk for hormone-sensitive cancers, research activities try to find alternatives. Phytoestrogens like genistein and resveratrol as well as other plant-derived compounds are capable of substituting for estrogens to some extent. Their effects on mesenchymal stem cells and the tissues derived therefrom have been investigated in vitro and in preclinical settings. Besides their well-known estrogenic, i.e. mainly antiresorptive effects on bone via estrogen receptor (ER) signalling, they also directly or indirectly affect osteogenic and adipogenic pathways. As a novel mechanism, phytoestrogens and plant-derived saponins and flavonoids like kaempferol and xanthohumol have been described to reciprocally affect the osteogenic versus the adipogenic differentiation pathway. Both, ER-mediated and other pathways mediate a shift towards osteogenesis by inhibiting PPARγ and C/EBPα, the key adipogenic transcription factors (TFs), while stimulating the key osteogenic TFs Runx2 and Sp7. Besides ER signalling, the broad spectrum of molecular mechanisms supporting osteogenesis comprises the modulation of PPARγ, Wnt/β-catenin, and Sirt1 signalling, which inversely influence the transcription or transactivation of osteogenic versus adipogenic TFs. Preventing the age- and hormone deficiency-related shift towards adipogenesis without provoking adverse estrogenic effects represents a very promising strategy for treating bone loss and other metabolic diseases beyond bone. Research on plant-derived compounds will have to be pursued in vitro as well as in preclinical studies and controlled clinical trials in humans are urgently needed. This article is part of a Special Issue entitled 'Phytoestrogens'.

  9. The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role of Labisia pumila in Prevention of Postmenopausal Osteoporosis

    PubMed Central

    Nadia, M. E.; Nazrun, A. S.; Norazlina, M.; Isa, N. M.; Norliza, M.; Ima Nirwana, S.

    2012-01-01

    Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis. PMID:22611381

  10. The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role of Labisia pumila in Prevention of Postmenopausal Osteoporosis.

    PubMed

    Nadia, M E; Nazrun, A S; Norazlina, M; Isa, N M; Norliza, M; Ima Nirwana, S

    2012-01-01

    Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.

  11. [Research progress of phytoestrogens-like chemical constituents in natural medicines].

    PubMed

    Yuan, Ting-Ting; Zhang, Nai-Dan; He, Yong-Jing; Li, Mei; Xu, Hong-Tao; Zhang, Qiao-Yan

    2014-12-01

    Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens. PMID:25911795

  12. [Research progress of phytoestrogens-like chemical constituents in natural medicines].

    PubMed

    Yuan, Ting-Ting; Zhang, Nai-Dan; He, Yong-Jing; Li, Mei; Xu, Hong-Tao; Zhang, Qiao-Yan

    2014-12-01

    Phytoestrogens, which can bind with estrogen receptor and produce estrogen-like effects, are a kind of nonsteroidal compound in plant. Phytoestrogens chemically include isoflavones, coumarins, lignans and other compounds. Phytoestrogens are selective estrogen receptor modulator, and have therapeutical effects on breast cancer, prostate cancer, cardiovascular disease, menopausal symptoms, osteoporosis and other disease, however, do not produce stimulatory hyperplasia effects on uterus, mammary glands and other tissues and organs with positive estrogen receptor. Long-term exposure or excessive use of phytoestrogens maybe affects male reproductive system and hematopoietic function of fetus. Some questions need to be further studied, such as evaluation criteria on biological activity, adverse effects, and action mechanism of phytoestrogen. This review covers plant sources, chemical structure, pharmacological activity and safety of phytoestrogens. It will provide a useful reference for intensive research and rational utilization the phytoestrogens.

  13. Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia.

    PubMed

    Jantaratnotai, Nattinee; Utaisincharoen, Pongsak; Sanvarinda, Pimtip; Thampithak, Anusorn; Sanvarinda, Yupin

    2013-10-01

    Microglial activation has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and HIV encephalopathy. Phytoestrogens have been shown to be neuroprotective in neurotoxicity models; however, their effect on microglia has not been well established. In the current study, we report that the soy phytoestrogens, genistein, daidzein, and coumestrol, decreased nitric oxide (NO) production induced by lipopolysaccharide (LPS) in the rat microglial cell line (HAPI). The levels of inducible NO synthase (iNOS) mRNA and protein expression were also reduced. Transcription factors known to govern iNOS expression including interferon regulatory factor-1 (IRF-1) and phosphorylated STAT1 were down regulated. These observations explain, at least in part, the inhibitory effect of phytoestrogens on NO production. The levels of monocyte chemoattractant protein-1 and interleukin-6 mRNA, proinflammatory chemokine and cytokine associated with various neurological disorders, were also reduced following LPS stimulation when HAPI cells were pretreated with phytoestrogens. Hence, genistein, daidzein, and coumestrol could serve as anti-inflammatory agents and may have beneficial effects in the treatment of neurodegenerative diseases.

  14. Morphology of spermatogenic and accessory cells in the mussel Modiolus kurilensis under environmental pollution.

    PubMed

    Yurchenko, Olga V; Vaschenko, Marina A

    2010-08-01

    A comparative light- and electron microscopic study of the male gonads of the bivalve mollusk Modiolus kurilensis from the reference and polluted sites in Amursky Bay (Sea of Japan) was conducted. Testicular acini in the mussels from the reference site had well-ordered structure (vertical spermatogenic columns located among the accessory cells bodies) whereas in the testes of the mollusks from the polluted site, the accessory and spermatogenic cell populations were disarranged. Mussels from the polluted station had about 26% of spermatogenic cells with marginal localization of nuclear chromatin, swollen outer nuclear membrane and heavily vacuolated cytoplasm and about 8% of spermatozoa with transformed or destructed acrosome; in mussels from the reference station, these values were close to zero. The accessory cells in the mussels from the polluted site were underdeveloped, and their phagocytic activity was inhibited. Our ultrastructural observations provide evidence that both spermatogenic and accessory cells are targets of environmental pollution in marine mussels.

  15. Phytoestrogens for menopausal bone loss and climacteric symptoms.

    PubMed

    Lagari, Violet S; Levis, Silvina

    2014-01-01

    Women have always looked for non-hormonal options to alleviate menopausal vasomotor symptoms and prevent menopausal bone loss. The use of complementary and alternative medicine for these purposes has particularly increased after the publication of the Women's Health Initiative's results suggesting that there might be more risks than benefits with hormone replacement. Phytoestrogens are plant-derived estrogens that, although less potent than estradiol, bind to the estrogen receptor and can function as estrogen agonists or antagonists. Soy isoflavones extracted from soy are the phytoestrogens most commonly used by menopausal women. Because typical Western diets are low in phytoestrogens and taking into account the general difficulty in changing dietary habits, most clinical trials in Western women have used isoflavone-fortified foods or isoflavone tablets. Although some women might experience a reduction in the frequency or severity of hot flashes, most studies point towards the lack of effectiveness of isoflavones derived from soy or red clover, even in large doses, in the prevention of hot flashes and menopausal bone loss. This article is part of a Special Issue entitled 'Phytoestrogens'.

  16. Phytoestrogens for menopausal bone loss and climacteric symptoms.

    PubMed

    Lagari, Violet S; Levis, Silvina

    2014-01-01

    Women have always looked for non-hormonal options to alleviate menopausal vasomotor symptoms and prevent menopausal bone loss. The use of complementary and alternative medicine for these purposes has particularly increased after the publication of the Women's Health Initiative's results suggesting that there might be more risks than benefits with hormone replacement. Phytoestrogens are plant-derived estrogens that, although less potent than estradiol, bind to the estrogen receptor and can function as estrogen agonists or antagonists. Soy isoflavones extracted from soy are the phytoestrogens most commonly used by menopausal women. Because typical Western diets are low in phytoestrogens and taking into account the general difficulty in changing dietary habits, most clinical trials in Western women have used isoflavone-fortified foods or isoflavone tablets. Although some women might experience a reduction in the frequency or severity of hot flashes, most studies point towards the lack of effectiveness of isoflavones derived from soy or red clover, even in large doses, in the prevention of hot flashes and menopausal bone loss. This article is part of a Special Issue entitled 'Phytoestrogens'. PMID:23246986

  17. Determination of Phytoestrogen Content in Fresh-Cut Legume Forage

    PubMed Central

    Hloucalová, Pavlína; Skládanka, Jiří; Horký, Pavel; Klejdus, Bořivoj; Pelikán, Jan; Knotová, Daniela

    2016-01-01

    Simple Summary Phytoestrogens comprise a group of substances negatively influencing the development and function of animal reproductive organs. Their appearance in forage crops can reduce feeding values, cause dietary disorders, and lead to animal health damage. This study evaluated the occurrence of individual phytoestrogens in various species of annual and perennial legumes and their levels in dry forage. It appeared that feeding large amounts of red clover presents a potential risk, but red clover can be replaced with the annual Persian clover, in which markedly lower phytoestrogen levels were detected. Abstract The aim of the study was to determine phytoestrogen content in fresh-cut legume forage. This issue has been much discussed in recent years in connection with the health and safety of feedstuffs and thus livestock health. The experiments were carried out on two experimental plots at Troubsko and Vatín, Czech Republic during June and July in 2015. Samples were collected of the four forage legume species perennial red clover (variety “Amos”), alfalfa (variety “Holyně”), and annuals Persian clover and Alexandrian clover. Forage was sampled twice at regular three to four day intervals leading up to harvest and a third time on the day of harvest. Fresh and wilted material was analyzed using liquid chromatography–mass spectrometry (LC-MS). Higher levels (p < 0.05) of isoflavones biochanin A (3.697 mg·g−1 of dry weight) and formononetin (4.315 mg·g−1 of dry weight) were found in red clover than in other species. The highest isoflavone content was detected in red clover, reaching 1.001% of dry matter (p < 0.05), representing a risk for occurrence of reproduction problems and inhibited secretion of animal estrogen. The phytoestrogen content was particularly increased in wilted forage. Significant isoflavone reduction was observed over three to four day intervals leading up to harvest. PMID:27429009

  18. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease.

    PubMed

    Gencel, V B; Benjamin, M M; Bahou, S N; Khalil, R A

    2012-02-01

    Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of

  19. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    PubMed

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-01

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

  20. Behavioral and spermatogenic hybrid male breakdown in Nasonia.

    PubMed

    Clark, M E; O'Hara, F P; Chawla, A; Werren, J H

    2010-03-01

    Several reproductive barriers exist within the Nasonia species complex, including allopatry, premating behavioral isolation, postzygotic inviability and Wolbachia-induced cytoplasmic incompatibility. Here we show that hybrid males suffer two additional reproductive disadvantages, an inability to properly court females and decreased sperm production. Hybrid behavioral sterility, characterized by a reduced ability of hybrids to perform necessary courtship behaviors, occurs in hybrids between two species of Nasonia. Hybrid males produced in crosses between N. vitripennis and N. giraulti courted females at a reduced frequency (23-69%), compared with wild-type N. vitripennis and N. giraulti males (>93%). Reduced courtship frequency was not a simple function of inactivity among hybrids. A strong effect of cytoplasmic (mitochondrial) background was also found in N. vitripennis and N. giraulti crosses; F2 hybrids with giraulti cytoplasm showing reduced ability at most stages of courtship. Hybrids produced between a younger species pair, N. giraulti and N. longicornis, were behaviorally fertile. All males possessed motile sperm, but sperm production is greatly reduced in hybrids between the older species pair, N. vitripennis and N. giraulti. This effect on hybrid males, lowered sperm counts rather than nonfunctional sperm, is different from most described cases of hybrid male sterility, and may represent an earlier stage of hybrid sperm breakdown. The results add to previous studies of F2 hybrid inviability and behavioral sterility, and indicate that Wolbachia-induced hybrid incompatibility has arisen early in species divergence, relative to behavioral sterility and spermatogenic infertility.

  1. Ribonucleases endowed with specific toxicity for spermatogenic layers

    PubMed Central

    Matoušek, Josef; Kim, Jin-Soo; Souček, Josef; Rìha, Jan; Ribó, Marc; Leland, Peter A.; Raines, Ronald T.

    2010-01-01

    Bovine seminal ribonuclease (BS-RNase) is a dimer in which the subunits are cross-linked by disulfide bonds between Cys31 of one subunit and Cys32 of the other. Dimeric BS-RNase is resistant to ribonuclease inhibitor (RI), a protein endogenous to mammalian cells, and is toxic to a variety of cell types. Monomeric BS-RNase (like its homolog, RNase A) is bound tightly by RI and is not cytotoxic. The three-dimensional structure of the RI·RNase A complex suggests that carboxymethylation of C32S BS-RNase (to give MCM31) or C31S BS-RNase (MCM32) could diminish affinity for RI. We find that MCM31 and MCM32 are not only resistant to RI, but are also aspermatogenic to mice. In contrast to the aspermatogenic activity of dimeric BS-RNase, that of MCM31 and MCM32 is directed only at spermatogenic layers. Intratesticular injection of MCM31 or MCM32 affects neither the diameter of seminiferous tubules nor the weight of testes. Also in contrast to wild-type BS-RNase, MCM31 and MCM32 are not toxic to other cell types. Direct immunofluorescence reveals that MCM31 and MCM32 bind only to spermatogonia and primary spermatocytes. This cell specificity makes MCM31 and MCM32 of potential use in seminoma therapy and contraception. PMID:21399757

  2. The OECD program to validate the rat uterotrophic bioassay. Phase 2: dietary phytoestrogen analyses.

    PubMed Central

    Owens, William; Ashby, John; Odum, Jenny; Onyon, Lesley

    2003-01-01

    Many commercial laboratory diets have detectable levels of isoflavones (e.g., phytoestrogens such as genistein [GN]) that have weak estrogenic activity both in vitro and in vivo. During validation studies of the uterotrophic bioassay, diet samples from 20 participating laboratories were collected and analyzed for three major phytoestrogens: GN, daidzein (DN), and coumestrol (CM). Soy phytoestrogens GN and DN were found at total phytoestrogen levels from 100 to 540 microg/g laboratory diet; a forage phytoestrogen, CM, ranged from nondetectable to 4 microg/g laboratory diet. The phytoestrogen levels were compared with both baseline uterine weights of the control groups and with the relative uterine weight increase of groups administered two weak estrogen agonists: bisphenol A (BPA) and nonylphenol (NP). The comparison uses a working assumption of additivity among the phytoestrogens, despite several significant qualifications to this assumption, to estimate total genistein equivalents (TGE). Some evidence was found that phytoestrogen levels in the diet > 325-350 microg/g TGE could diminish the responsiveness of the uterotrophic bioassay to weak agonists. This was especially true for the case of the intact, immature female version of the uterotrophic bioassay, where higher food consumption relative to body weight leads to higher intakes of dietary phytoestrogens versus ovariectomized adults. This dietary level is sufficient in the immature female to approach a biological lowest observable effect level for GN of 40-50 mg/kg/day. These same data, however, show that low to moderate levels of dietary phytoestrogens do not substantially affect the responsiveness of the assay with weak estrogen receptor agonists such as NP and BPA. Therefore, laboratories conducting the uterotrophic bioassay for either research or regulatory purposes may routinely use diets containing levels of phytoestrogens < 325-350 microg/g TGE without impairing the responsiveness of the bioassay. PMID

  3. A review of phytoestrogens: their occurrence and fate in the environment.

    PubMed

    Liu, Ze-hua; Kanjo, Yoshinori; Mizutani, Satoshi

    2010-01-01

    Phytoestrogens are plant compounds with estrogenic activities. Many edible plants, some of which are common in the human diet, are rich in phytoestrogens. Almost all phytoestrogens eaten daily by people were reported partly recovered in urine or feces, which can be regarded as one of the main sources of their occurrence in municipal wastewaters. As they may act as one part of the endocrine disrupting compounds (EDCs) in water systems, some phytoestrogens have been monitored and detected in wastewater and other various environments. It is very difficult to monitor numerous unknown EDCs in complex wastewater samples, and it is helpful if some estimation of target EDCs can be done before monitoring. With this in mind, this review will: (1) summarize estrogenic activities or estrogenic potencies of phytoestrogens by different bioassays; (2) summarize daily urinary excretion rates of phytoestrogens by humans, and compare their urinary excretion rates to that of estrone, which suggests that most phytoestrogens may occur in municipal wastewaters; (3) collect and summarize published data on the occurrence and fate of phytoestrogens in various environments.

  4. Phytoestrogens and mitochondrial biogenesis in breast cancer. Influence of estrogen receptors ratio.

    PubMed

    Roca, Pilar; Sastre-Serra, Jorge; Nadal-Serrano, Mercedes; Pons, Daniel Gabriel; Blanquer-Rosselló, Ma del Mar; Oliver, Jordi

    2014-01-01

    Phytoestrogens were originally identified as compounds having a close similarity in structure to estrogens and harboring weak estrogen activity. The interest in phytoestrogens as potential therapeutic agents has recently risen in the field of oncology, since population based studies have linked phytoestrogens consumption with a decreased risk of mortality due to several types of cancer. This review departs from the main focus of these articles by describing recent advances in our understanding of phytoestrogen potential action on mitochondria, specifically on mitochondrial biogenesis, dynamics and functionality, as well as mitoptosis in breast cancer. Further studies are necessary to explain the effects of individual phytoestrogens on mitochondrial biogenesis and dynamics and for designing of new therapy targets for cancer treatment, nevertheless area promising therapeutic approach.

  5. Spermatogenic cycle length and sperm production in a feral pig species (collared peccary, Tayassu tajacu).

    PubMed

    Costa, Guilherme M J; Leal, Marcelo C; Silva, Jurupytan V; Ferreira, Ana Cássia S; Guimarães, Diva A; França, Luiz Renato de

    2010-01-01

    Although the collared peccary (Tayassu tajacu) is found throughout the Americas, with a high potential for domestication and commercial exploitation, there are few data on the reproductive biology of this mammalian species. The aim of the present study was to investigate testis structure, spermatogenic cycle length, Sertoli cell efficiency, and spermatogenic efficiency. Twelve adult peccaries were used for biometrical, histological, and stereological analyses; 3 of these peccaries received intratesticular injections of (3)H-thymidine for the determination of the duration of spermatogenesis. Testis weight and gonadosomatic index were 23.7 +/- 1.8 g and 0.2% +/- 0.1%, respectively. Seminiferous tubule volume density was 77.4% +/- 1.7%. Leydig cells occupied 12.8% +/- 1.8% of the testis parenchyma and presented a peculiar cytoarchitecture in the periphery of the seminiferous tubule lobes. The premeiotic, meiotic, and postmeiotic stage frequencies were very similar to those found for wild and domestic boars. The spermatogenic cycle and entire spermatogenic process (based on 4.5 cycles) lasted approximately 12.3 +/- 0.2 and 55.1 +/- 0.7 days, respectively. Daily sperm production per gram of testis in the collared peccary was approximately 23.4 +/- 2 x 10(6), which is similar to that of domestic and wild boars. The knowledge generated in the present study could be used in reproduction and animal improvement programs and provides important information that may be used for comparative reproductive biology with previously investigated mammalian species.

  6. HUMAN GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE-2 (GAPD2) GENE IS EXPRESSED SPECIFICALLY IN SPERMATOGENIC CELLS

    EPA Science Inventory

    Although the process of glycolysis is highly conserved in eukaryotes, several glycolytic enzymes have unique structural or functional features in spermatogenic cells. We previously identified and characterized the mouse complementary DNA (cDNA) and a gene for 1 of these enzymes, ...

  7. EXPRESSION OF THE SPERMATOGENIC CELL-SPECIFIC GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE (GAPDS) IN RAT TESTIS

    EPA Science Inventory

    The spermatogenic cell-specific variant of glyceraldehyde 3-phosphate dehydrogenase (GAPDS) has been cloned from a rat testis cDNA library and its pattern of expression determined. A 1417 nucleotide cDNA has been found to encode an enzyme with substantial homology to mouse GAPDS...

  8. Spermatogenic cycle length and sperm production in the freshwater turtle Kinosternon scorpioides.

    PubMed

    Sousa, Alana Lislea; Campos-Junior, Paulo Henrique Almeida; Costa, Guilherme Mattos Jardim; de França, Luiz Renato

    2014-02-01

    Kinosternon scorpioides is a Brazilian freshwater turtle that belongs to the class Reptilia, encompassing almost 10,000 species. Nevertheless, very little is known about the testicular quantitative parameters, particularly those related to spermatogenesis, in this vertebrate class. Our main objectives were to investigate in detail the structure and function of the testis in K. scorpioides, particularly the aspects related to spermatogenic cycle length and Sertoli cell (SC) and spermatogenic efficiencies. Nine sexually mature turtles were examined, and intraperitoneal bromodeoxyuridine injections were administered to estimate duration of spermatogenesis. Based on the acrosome development in spermatids and the overall germ cell associations, 10 stages of the seminiferous epithelium cycle were characterized. Similar to birds, humans, and some primate species, several stages were observed per seminiferous tubule cross-sections. One spermatogenic cycle and the entire spermatogenic process lasted, respectively, 12 and 53 days. The SC efficiency (number of round spermatids per SC) and daily sperm production per gram of testis were, respectively, 20 and 40 million spermatids. As established for mammals, our findings suggest that SC efficiency is also a critical determinant of sperm production in reptiles. To our knowledge, this is the first study to investigate the kinetics of spermatogenesis and testis function in any reptilian species. Besides allowing a better understanding of reproductive biology in reptiles, these data will be useful in comparative studies. Moreover, these results could provide the basis for investigations related to the evaluation of spermatogonial stem cell physiology niche in Kinosternon scorpioides. PMID:24403547

  9. The effect of phytoestrogens on the female genital tract

    PubMed Central

    Burton, J L; Wells, M

    2002-01-01

    Environmental oestrogens have been implicated in the pathogenesis of hormonally treated cancers (such as breast and prostate cancer), male infertility, and abnormalities of the male and female reproductive tracts. They may be derived from plants (phytoestrogens), pharmaceuticals, or other synthetic compounds not originally intended to have oestrogenic activity (including soy based infant formulas). This review will discuss the evidence from both animal studies and humans for an effect of these ubiquitous compounds on the development of the human female genital tract, in addition to prolonging the menstrual cycle, alleviating symptoms of the menopause, and protecting against the development of endometrial carcinoma. PMID:12037019

  10. Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility.

    PubMed

    Qin, Yufeng; Du, Guizhen; Chen, Minjian; Hu, Weiyue; Lu, Chuncheng; Wu, Wei; Hang, Bo; Zhou, Zuomin; Wang, Xinru; Xia, Yankai

    2014-08-01

    Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10(-8)). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10(-4), 1.14 × 10(-3), 3.55 × 10(-3), respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC's effects on male reproduction.

  11. Prevention of bone resorption by intake of phytoestrogens in postmenopausal women: a meta-analysis.

    PubMed

    Salari Sharif, Pooneh; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2011-09-01

    Phytoestrogens as selective estrogen receptor modulators like compounds may consider as a therapeutic option in osteoporosis. In this regard, the effect of phytoestrogens on bone biomarkers was examined in several trials which their results are controversial. We aimed this meta-analysis to evaluate the net effect of phytoestrogens on bone markers. A thorough search was conducted from 2000 to 2010 in English articles. All randomized clinical trials were reviewed, and finally, 11 eligible randomized clinical trials were selected for meta-analysis. Totally 1,252 postmenopausal women were enrolled in the study by considering the changes of pyridinoline (Pyd), desoxypyridinoline (Dpyd), bone alkaline phosphatase, and osteocalcin concentrations in urine and serum after phytoestrogens consumption. The urine Pyd and Dpyd levels decreased significantly in phytoestrogens consumers. Effect size and effect size for weighted mean difference of urine Pyd levels showed -1.229171 (95% confidence interval (CI) = -1.927639 to -0.530703) and -9.780623 (95% CI = -14.240401 to -5.320845), respectively, a significant results in comparison to control group and significant results for Dpyd -0.520132 (95% CI = -0.871988 to -0.168275) and -0.818582 (95% CI = -1.247758 to -0.389407), respectively. Meta-analysis indicates that phytoestrogens intake can prevent bone resorption, but its benefits on bone formation are not significant. This favorable effect was observed in low doses and in at least 3 weeks of phytoestrogens intake.

  12. Determination of Phytoestrogen Content in Fresh-Cut Legume Forage.

    PubMed

    Hloucalová, Pavlína; Skládanka, Jiří; Horký, Pavel; Klejdus, Bořivoj; Pelikán, Jan; Knotová, Daniela

    2016-01-01

    The aim of the study was to determine phytoestrogen content in fresh-cut legume forage. This issue has been much discussed in recent years in connection with the health and safety of feedstuffs and thus livestock health. The experiments were carried out on two experimental plots at Troubsko and Vatín, Czech Republic during June and July in 2015. Samples were collected of the four forage legume species perennial red clover (variety "Amos"), alfalfa (variety "Holyně"), and annuals Persian clover and Alexandrian clover. Forage was sampled twice at regular three to four day intervals leading up to harvest and a third time on the day of harvest. Fresh and wilted material was analyzed using liquid chromatography-mass spectrometry (LC-MS). Higher levels ( p < 0.05) of isoflavones biochanin A (3.697 mg·g (-1) of dry weight) and formononetin (4.315 mg·g (-1) of dry weight) were found in red clover than in other species. The highest isoflavone content was detected in red clover, reaching 1.001% of dry matter ( p < 0.05), representing a risk for occurrence of reproduction problems and inhibited secretion of animal estrogen. The phytoestrogen content was particularly increased in wilted forage. Significant isoflavone reduction was observed over three to four day intervals leading up to harvest. PMID:27429009

  13. Medical applications of phytoestrogens from the Thai herb Pueraria mirifica.

    PubMed

    Malaivijitnond, Suchinda

    2012-03-01

    Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand. It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years. Indeed, it has been claimed that P. mirifica contains active phytoestrogens (plant substances with estrogen-like activity). Using high performance liquid chromatography, at least 17 phytoestrogens, mainly isoflavones, have been isolated. Thus, fairly considerable scientific researches, both in vitro in cell lines and in vivo in various species of animals including humans, have been conducted to date to address its estrogenic activity on the reproductive organs, bones, cardiovascular diseases and other climacteric related symptoms. The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed. In general, P. mirifica could be applicable for preventing, or as a therapeutic for, the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men. However, the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.

  14. Systematic review and meta-analysis of the bone protective effect of phytoestrogens on osteoporosis in ovariectomized rats.

    PubMed

    Fu, Song-wen; Zeng, Gao-feng; Zong, Shao-hui; Zhang, Zhi-yong; Zou, Bin; Fang, Ye; Lu, Li; Xiao, De-qiang

    2014-06-01

    Phytoestrogens are candidate drugs for the treatment of osteoporosis. Many experiments have been designed to investigate the preventive effects of phytoestrogens for osteoporosis; however, it is easy for a single dissenting result from animal experiments to mislead clinical investigations. Herein, we use meta-analysis to assess the evidence for a protective effect of phytoestrogens on ovariectomized rat models of osteopenia. With respect to osteoporosis, PubMed and Web of Science were searched from January 2000 to March 2013 for relevant studies of phytoestrogens in ovariectomized rats. Two reviewers independently selected and assessed the studies. Data were aggregated using a random effects model. Meta-analysis revealed that the phytoestrogen treatment group demonstrated a significantly higher femur bone mineral density and trabecular bone and lower bone turnover markers (serum alkaline phosphatase and serum osteocalcin) compared with the control ovariectomized group, thus showing a bone protective effect of phytoestrogens in ovariectomized rats. Subsequent sensitivity analyses indicated that the effect of phytoestrogens on serum alkaline phosphatase and serum osteocalcin are not robust. Despite the high heterogeneity in the systematic review of animal experiments, the present results indicated that phytoestrogens may offer the most potential for the prevention of bone loss by reducing the expected loss of trabecular bone and bone mineral density. Their effects are likely due to inhibition of bone resorption, but their benefits on bone formation are still unclear. Further studies are needed to assess the effect of phytoestrogens on bone formation and the efficacy and safety of individual phytoestrogens.

  15. ADULT EXPOSURE TO PHYTOESTROGEN APIGENIN RESULTS IN CHANGES IN ENDOCRINE PARAMETERS BUT FAILS TO ALTER FECUNDITY

    EPA Science Inventory

    Plant-derived estrogens offer the opportunity to investigate the potential for weakly estrogenic compounds to influence endocrine function and reproduction. The presence of these phytoestrogens in foods, and agricultural and industrial runoff has the potential to increase the tot...

  16. Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens.

    PubMed

    Boberg, Julie; Mandrup, Karen Riiber; Jacobsen, Pernille Rosenskjold; Isling, Louise Krag; Hadrup, Niels; Berthelsen, Line; Elleby, Anders; Kiersgaard, Maria; Vinggaard, Anne Marie; Hass, Ulla; Nellemann, Christine

    2013-09-01

    Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based.

  17. Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women.

    PubMed

    Sobenin, Igor A; Myasoedova, Veronica A; Orekhov, Alexander N

    2016-01-01

    Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement therapy prevents the development of atherosclerosis in menopausal women. However, the results of the largest international trials involving thousands of women have completely destroyed this hope. The modern perspective for the development of effective and safe drugs to enhance the quality of life and to prevent atherosclerosis progression in postmenopausal women may be the use of phytoestrogens, the substances of plant origin possessing estrogen- like effects, and possibly providing anti-atherosclerotic and anti-climacteric action. Phytoestrogens are often considered as a possible alternative to hormone replacement therapy, since they are believed to alleviate some symptoms of menopause. However, until now there is no exact evidence to consider phytoestrogens as the substances that protect women from atherosclerosis. It should be noted that the data from clinical studies with inconsistent results are mainly inconsistent per se, as most of the studies have serious limitations due to the study design and the participants' compliance. Nevertheless, there is a substantial evidence that phytoestrogens have the potential to address several conditions and diseases associated with the menopausal transition. Phytoestrogens, at least, can potentially reduce atherosclerosis and atherosclerosis-related diseases through multiple mechanisms, by regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system. However, a skepticism exists concerning the true potential of phytoestrogens to beneficially modify these processes. An analysis of findings from supplementing the diet with phytoestrogens has failed, in general, to

  18. Responses of Spermatogenous Tissue and Mechanisms of Their Development Upon Cytostatic Exposure.

    PubMed

    Dygai, A M; Chaikovskii, A V; Zhdanov, V V; Zyuz'kov, G N; Stavrova, L A; Udut, V V; Miroshnichenko, L A; Simanina, E V; Borovskaya, T G; Poluektova, M E

    2015-10-01

    A decrease in the total number of sperm cells and reduction of spermatogonium population were observed upon cytostatic damage of spermatogenous tissue caused by single paclitaxel administration. It was established that the paclitaxel-induced damage to the testicular tissue is underlain by reduction of its regenerative potential consisting in depletion of regional precursor pool. Changes in functional activity of progenitor cells were caused not only by direct action of paclitaxel, but also by suppression of the secretory function of the tissue microenvironment.

  19. Phytoestrogens Activate the Estrogen Receptor in HepG2 Cells.

    PubMed

    Kelly, Lynne A

    2016-01-01

    Phytoestrogens are popular alternatives to estrogen therapy however their effects on hemostasis in postmenopausal women are unknown. This chapter describes a protocol to determine the effect of the phytoestrogens genistein, daidzein and equol, on the expression of key genes from the hemostatic system in human hepatocyte cell models and to determine the role of estrogen receptors in mediating any response seen using in vitro culture systems and Taqman(®) gene expression analysis. PMID:26585156

  20. Phytoestrogens Activate the Estrogen Receptor in HepG2 Cells.

    PubMed

    Kelly, Lynne A

    2016-01-01

    Phytoestrogens are popular alternatives to estrogen therapy however their effects on hemostasis in postmenopausal women are unknown. This chapter describes a protocol to determine the effect of the phytoestrogens genistein, daidzein and equol, on the expression of key genes from the hemostatic system in human hepatocyte cell models and to determine the role of estrogen receptors in mediating any response seen using in vitro culture systems and Taqman(®) gene expression analysis.

  1. New concepts, experimental approaches, and dereplication strategies for the discovery of novel phytoestrogens from natural sources.

    PubMed

    Michel, Thomas; Halabalaki, Maria; Skaltsounis, Alexios-Leandros

    2013-05-01

    Phytoestrogens constitute an attractive research topic due to their estrogenic profile and their biological involvement in woman's health. Therefore, numerous studies are currently performed in natural products chemistry area aiming at the discovery of novel phytoestrogens. The main classes of phytoestrogens are flavonoids (flavonols, flavanones), isoflavonoids (isoflavones, coumestans), lignans, stilbenoids as well as miscellaneous chemical groups abundant in several edible and/or medicinal plants, belonging mostly to the Leguminosae family. As for other bioactives, the detection of new structures and more potent plant-derived phytoestrogens typically follows the general approaches currently available in the natural product discovery process. Plant-based approaches selected from traditional medicine knowledge and bioguided concepts are routinely employed. However, these approaches are associated with serious disadvantages such as time-consuming, repeated, and labor intensive processes as well as lack of specificity and reproducibility. In recent years, the natural products chemistry became more technology-driven, and several different strategies have been developed. Structure-oriented procedures and miniaturized approaches employing advanced hyphenated analytical platforms have recently emerged. They facilitate significantly not only the discovery of novel phytoestrogens but also the dereplication procedure leading to the anticipation of major drawbacks in natural products discovery. In this review, apart from the traditional concepts followed in phytochemistry for the discovery of novel biologically active compounds, recent applications in the field of extraction, analysis, fractionation, and identification of phytoestrogens will be discussed. Moreover, specific methodologies combining identification of actives and biological evaluation in parallel, such as liquid chromatography-biochemical detection, frontal affinity chromatography-mass spectrometry and pulsed

  2. The Spermatogenic Effect of Yacon Extract and Its Constituents and Their Inhibition Effect of Testosterone Metabolism

    PubMed Central

    Park, Jeong Sook; Han, Kun

    2013-01-01

    We screened the pharmacological effects of a 50% ethanol extract of Yacon tubers and leaves on spermatogenesis in rats. As a result, we found that Yacon tuber extracts increased sperm number and serum testosterone level in rats. It has been reported that the crude extract of Yacon tubers and leaves contain phenolic acids, such as, chlorogenic acid, ferulic acid and caffeic acid by HPLC/MS analysis. We were interested in the contributions made by phenolic acid, particularly chlorogenic acid of Yacon tuber extract to the spermatogenic activity. After administering Yacon tuber extract or chlorogenic acid to rats for 5 weeks, numbers of sperm in epididymis were increased by 34% and 20%, respectively. We also administered ferulic acid, which has been reported to be a metabolite of chlorogenic acid and a constituent of Yacon tuber extract to investigate its spermatogenic activity in rats. Yacon tuber extract and ferulic acid increased sperm numbers by 43% and 37%, respectively. And, Yacon tuber extract, and chlorogenic acid showed significantly inhibition effect of testoeterone degradation in rat liver homogenate. We considered that the spermatogenic effect of Yacon tuber extract might be related to phenolic compounds and their inhibitory effect of testosterone degradation. Yacon showed the possibility as ameliorable agents of infertility by sperm deficiency and late onset hypogonadism syndrome with low level of testosterone. PMID:24009874

  3. Cell population indexes of spermatogenic yield and testicular sperm reserves in adult jaguars (Panthera onca).

    PubMed

    de Azevedo, Maria Helena Ferreira; de Paula, Tarcízio Antônio Rego; Matta, Sérgio Luis Pinto da; Fonseca, Cláudio César; da Costa, Eduardo Paulino; Costa, Deiler Sampaio; Peixoto, Juliano Vogas

    2010-03-01

    The intrinsic yield of spermatogenesis and supporting capacity of Sertoli cells are the desirable indicators of sperm production in a species. The objective of the present study was to quantify intrinsic yield and the Sertoli cell index in the spermatogenic process and estimate testicular sperm reserves by histological assessment of fragments obtained by testicular biopsy of five adult jaguars in captivity. The testicular fragments were fixed in 4% glutaric aldehyde, dehydrated at increasing alcohol concentrations, included into hydroxyethyl methacrylate, and were cut into 4 microm thickness. In the seminiferous epithelium of the jaguar, 9.2 primary spermatocytes in pre-leptotene were produced by "A" spermatogonia. During the meiotic divisions only 3.2 spermatids were produced by a primary spermatocyte. The general spermatogenic yield of the jaguar was about 23.4 cells and each Sertoli cell was able to maintain about 19.2 germ cells, 11 of them were round spermatids. In each seminiferous epithelium cycle about 166 million spermatozoa were produced by each gram of testicular tissue. In adult jaguars, the general spermatogenic yield was similar to the yield observed in pumas, greater than that observed for the domestic cat, but less compared to most domestic animals.

  4. Natural male contraceptive: phytochemical investigation and anti-spermatogenic activity of Pistia stratiotes Linn.

    PubMed

    Singh, Kiran; Dubey, Bidhyut Kumar; Tripathi, Avinash C; Singh, Ajeet Pal; Saraf, Shailendra K

    2014-01-01

    This work is an attempt to explore the anti-spermatogenic activity of Pistia stratiotes and to investigate it as a male contraceptive. The prepared extracts were screened for the presence of alkaloids, glycosides, steroids, flavonoids, saponin and phenolic compounds. To assess the anti-spermatogenic activity, mice were orally administered with the various extracts of P. stratiotes (dose: 100 and 200 mg/kg body weight/day, for 45 days) and the most active, ethanolic extract was subjected to the isolation of phytoconstituent responsible for the activity. Diethyl ether fraction of ethanolic extract was taken to isolate a saponin, sitosterol-3-O-[2,4-di-O-acetyl-6-O-stearyl-β-D-glucopyranoside]. Anti-spermatogenic activity of the isolated saponin was evaluated at a dose of 50 mg/kg body weight/day, for 45 days. The treatment caused significant decrease (P < 0.01) in the weight of reproductive organs (testis, epididymis and seminal vesicle). The sperm count, sperm viability and serum testosterone levels were significantly lowered compared with that of the control group.

  5. Spermatogenic structure and fertility of Mus musculus after exposure of mangosteen (Garcinia mangostana L) pericarp extract

    NASA Astrophysics Data System (ADS)

    Hayati, Alfiah; Agustin, Melia Eka; Rokhimaningrum, Farida Ayu; Adro'i, Hasan; Darmanto, Win

    2016-03-01

    This study aimed to determine the effect of mangosteen (Garcinia mangostana L.) pericarp extract on spermatogenics number, seminiferous tubules sized, profile protein of epididymal and testicular sperm, and fertility of mice (Mus musculus). Fourty two male mice strain BALB/C was divided equally into 7 groups. The control group was given 0.05 ml of 0.05% CMC solution. Three group were given mangosteen pericarp extract at various doses (75, 100 and 150 mg/kg body weight, respectively) for 7 days, while the other three groups were given the same extract dose for 35 days. Parameters evaluated on histological of spermatogonia, spermatocytes, round spermatids, seminiferous tubule diameter, and thickness of germinal epithelium, analysis of testicular and epidydimal protein profile with SDS-Page, and than fertility test on female mice. The results showed that mangosteen pericarp extract at 75 and 100 mg/kg dose for 7 days had no effect on spermatogenics number and seminiferous tubule sizes, but the treatment dose of 150 mg/kg for 7 days and all treatment (doses of 75, 100, and 150 mg/kg) for 35 days led to significant decrease on the number of spermatogenics and seminiferous tubule sizes; effect on protein profiles testicular and epididymal sperm; and lower fertilization.

  6. Spermatogenic Cell-Specific Gene Mutation in Mice via CRISPR-Cas9.

    PubMed

    Bai, Meizhu; Liang, Dan; Wang, Yinghua; Li, Qing; Wu, Yuxuan; Li, Jinsong

    2016-05-20

    Tissue-specific knockout technology enables the analysis of the gene function in specific tissues in adult mammals. However, conventional strategy for producing tissue-specific knockout mice is a time- and labor-consuming process, restricting rapid study of the gene function in vivo. CRISPR-Cas9 system from bacteria is a simple and efficient gene-editing technique, which has enabled rapid generation of gene knockout lines in mouse by direct injection of CRISPR-Cas9 into zygotes. Here, we demonstrate CRISPR-Cas9-mediated spermatogenic cell-specific disruption of Scp3 gene in testes in one step. We first generated transgenic mice by pronuclear injection of a plasmid containing Hspa2 promoter driving Cas9 expression and showed Cas9 specific expression in spermatogenic cells. We then produced transgenic mice carrying Hspa2 promoter driven Cas9 and constitutive expressed sgRNA targeting Scp3 gene. Male founders were infertile due to developmental arrest of spermatogenic cells while female founders could produce progeny normally. Consistently, male progeny from female founders were infertile and females could transmit the transgenes to the next generation. Our study establishes a CRISPR-Cas9-based one-step strategy to analyze the gene function in adult tissues by a temporal-spatial pattern.

  7. Extraction and quantification of phytoestrogens in foods using automated solid-phase extraction and LC/MS/MS.

    PubMed

    Kuhnle, Gunter G C; Dell'aquila, Caterina; Low, Yen-Ling; Kussmaul, Michaela; Bingham, Sheila A

    2007-12-01

    Phytoestrogens are a group of polyphenolic plant metabolites that can induce biological responses. Their bioactivity is based on their similarity to 17beta-estradiol and their ability to bind to the beta-estrogen receptor. Although epidemiological data are inconclusive, phytoestrogens are considered to be beneficial for a variety of conditions, for example, hormone-related cancers like breast and prostate cancer. To investigate the biological effects of these compounds and to assess the exposure of larger cohorts or the general public, reliable data on the phytoestrogen content of food is necessary. Previously, food analysis for phytoestrogens was performed using either HPLC-UV or GC/MS. Here, we describe the development of the first generic method for the analysis of phytoestrogens in food, using automated solid-phase extraction and liquid chromatography-tandem mass spectrometry. The presented method shows a good reproducibility and can be easily adapted to other phytoestrogens if required.

  8. Phytoestrogens in the prevention of postmenopausal bone loss.

    PubMed

    Lagari, Violet S; Levis, Silvina

    2013-01-01

    Postmenopausal osteoporosis is a condition associated with low bone mass resulting from the increased bone resorption that occurs following a decline in estrogen levels. Phytoestrogens are plant-derived compounds that have affinity to the estrogen receptor and are able to act as either estrogen agonists or antagonists. Because of their structural similarity to 17-beta-estradiol, they have been studied extensively for their role in the prevention of postmenopausal bone loss. An extensive number of studies employing different types of isoflavone preparations (including soy foods, soy-enriched foods, and soy isoflavone tablets) have been conducted in a wide range of populations, including Western and Asian women. Although there is considerable variability in study design and duration, study population, type of soy isoflavone employed in the intervention, and study outcomes, the evidence points to a lack of a protective role of soy isoflavones in the prevention of postmenopausal bone loss.

  9. Serum levels of phytoestrogens as biomarkers of intake in Mexican women.

    PubMed

    Palma-Duran, Susana Alejandra; Caire-Juvera, Graciela; Robles-Burgeño, María del Refugio; Ortega-Vélez, María Isabel; Gutiérrez-Coronado, María de Lourdes; Almada, María del Carmen Bermúdez; Chávez-Suárez, Karina; Campa-Siqueiros, Melissa; Grajeda-Cota, Patricia; Saucedo-Tamayo, María del Socorro; Valenzuela-Quintanar, Ana Isabel

    2015-01-01

    Phytoestrogens have generated interest in human health in view of their potential effect to reduce the risk of developing chronic diseases. Serum levels of phytoestrogens have been proposed as an alternative to measure the exposure of phytoestrogens. We evaluated the use of serum as a biomarker of phytoestrogen's intake in healthy women. Phytoestrogens in serum (luteolin, kaempferol, equol, biochanin A, formononetin, quercetin, naringenin, coumestrol, secoisolariciresinol, genistein, matairesinol, enterolactone, enterodiol, daidzein, glycitein and resveratrol) were analyzed by HPLC-ESI-MS. Subjects were asked to recall all foods and beverages consumed the previous 24 h. Association of dietary intake and serum concentrations was performed by Spearman correlation. Correlations were found for naringenin (r = 0.47, p < 0.001), luteolin (r = 0.4 p < 0.001), genistein (r = 0.32, p < 0.01) enterolactone (r = 0.35, p = 0.0553), coumestrol (r = 0.26, p = 0.0835) and resveratrol (r = 0.29, p = 0.0517). Serum levels as biomarkers of intake along with a 24-h recall would be useful in order to investigate the relationship between phytoestrogens and health.

  10. Breast cancer cell apoptosis with phytoestrogens is dependent on an estrogen-deprived state.

    PubMed

    Obiorah, Ifeyinwa E; Fan, Ping; Jordan, V Craig

    2014-09-01

    Phytoestrogens have been investigated as natural alternatives to hormone replacement therapy and their potential as chemopreventive agents. We investigated the effects of equol, genistein, and coumestrol on cell growth in fully estrogenized MCF7 cells, simulating the perimenopausal state, and long-term estrogen-deprived MCF7:5C cells, which simulate the postmenopausal state of a woman after years of estrogen deprivation, and compared the effects with that of steroidal estrogens: 17β estradiol (E2) and equilin present in conjugated equine estrogen. Steroidal and phytoestrogens induce proliferation of MCF7 cells at physiologic concentrations but inhibit the growth and induce apoptosis of MCF7:5C cells. Although steroidal and phytoestrogens induce estrogen-responsive genes, their antiproliferative and apoptotic effects are mediated through the estrogen receptor. Knockdown of ERα using siRNA blocks all estrogen-induced apoptosis and growth inhibition. Phytoestrogens induce endoplasmic reticulum stress and inflammatory response stress-related genes in a comparable manner as the steroidal estrogens. Inhibition of inflammation using dexamethasone blocked both steroidal- and phytoestrogen-induced apoptosis and growth inhibition as well as their ability to induce apoptotic genes. Together, this suggests that phytoestrogens can potentially be used as chemopreventive agents in older postmenopausal women but caution should be exercised when used in conjunction with steroidal anti-inflammatory agents due to their antiapoptotic effects.

  11. Beneficial effects of phytoestrogens and their metabolites produced by intestinal microflora on bone health.

    PubMed

    Chiang, Shen-Shih; Pan, Tzu-Ming

    2013-02-01

    Phytoestrogens are a class of bioactive compounds derived from plants and exert various estrogenic and antiestrogenic effects. Estrogen deficiency osteoporosis has become a serious problem in elderly women. The use of ovariectomized (OVX) rat or mice models to simulate the postmenopausal condition is well established. This review aimed to clarify the sources, biochemistry, absorption, metabolism, and mode of action of phytoestrogens on bone health in intervention studies. In vitro, phytoestrogens promote protein synthesis, osteoprotegerin/receptor activation of nuclear factor-kappa B ligand ratio, and mineralization by osteoblast-like cells (MC3T3-E1). In the OVX murine model, administration of phytoestrogens can inhibit differentiation and activation of osteoclasts, expression of tartrate-resistant acid phosphatase, and secretion of pyridinoline compound. Phytoestrogens also enhance bone formation and increase bone mineral density and levels of alkaline phosphatase, osteocalcin, osteopontin, and α1(I) collagen. Results of mechanistic studies have indicated that phytoestrogens suppress the rate of bone resorption and enhance the rate of bone formation.

  12. Dietary withdrawal of phytoestrogens resulted in higher gene expression of 3-beta-HSD and ARO but lower 5-alpha-R-1 in male rats.

    PubMed

    Andreoli, María F; Stoker, Cora; Rossetti, María F; Lazzarino, Gisela P; Luque, Enrique H; Ramos, Jorge G

    2016-09-01

    Removing dietary phytoestrogens causes obesity and diabetes in adult male rats. Based on the facts that hypothalamic food intake control is disrupted in phytoestrogen-deprived animals and that several steroids affect food intake, we hypothesized that phytoestrogen withdrawal alters the expression of hypothalamic steroidogenic enzymes. Male Wistar rats fed with a high-phytoestrogen diet from conception to adulthood were subjected to phytoestrogen withdrawal by feeding them a low-phytoestrogen diet or a high-phytoestrogen, high-fat diet. Withdrawal of dietary phytoestrogens increased 3β-hydroxysteroid dehydrogenase and P450 aromatase gene expression and decreased those of 5α-reductase-1. This is a direct effect of the lack of dietary phytoestrogens and not a consequence of obesity, as it was not observed in high-fat-fed rats. Phytoestrogen withdrawal and high-fat diet intake reduced hypothalamic expression of estrogen receptor (ER)α correlated with low levels of ERα-O, ERα-OS, and ERα-OT transcripts. Variations in gene expression of steroidogenic enzymes may affect the content of neurosteroids. As neurosteroids are related to food intake control, the changes observed may be a novel mechanism in the regulation of energy balance in obese phytoestrogen-deprived animals. In rats, steroidogenesis and ER signaling appear to be altered by phytoestrogen withdrawal in the rat. The ubiquity of phytoestrogens in the diet and changing intakes or withdrawal suggest that aspects of human health could be affected based on the rat and warrant further research. PMID:27632921

  13. Dietary withdrawal of phytoestrogens resulted in higher gene expression of 3-beta-HSD and ARO but lower 5-alpha-R-1 in male rats.

    PubMed

    Andreoli, María F; Stoker, Cora; Rossetti, María F; Lazzarino, Gisela P; Luque, Enrique H; Ramos, Jorge G

    2016-09-01

    Removing dietary phytoestrogens causes obesity and diabetes in adult male rats. Based on the facts that hypothalamic food intake control is disrupted in phytoestrogen-deprived animals and that several steroids affect food intake, we hypothesized that phytoestrogen withdrawal alters the expression of hypothalamic steroidogenic enzymes. Male Wistar rats fed with a high-phytoestrogen diet from conception to adulthood were subjected to phytoestrogen withdrawal by feeding them a low-phytoestrogen diet or a high-phytoestrogen, high-fat diet. Withdrawal of dietary phytoestrogens increased 3β-hydroxysteroid dehydrogenase and P450 aromatase gene expression and decreased those of 5α-reductase-1. This is a direct effect of the lack of dietary phytoestrogens and not a consequence of obesity, as it was not observed in high-fat-fed rats. Phytoestrogen withdrawal and high-fat diet intake reduced hypothalamic expression of estrogen receptor (ER)α correlated with low levels of ERα-O, ERα-OS, and ERα-OT transcripts. Variations in gene expression of steroidogenic enzymes may affect the content of neurosteroids. As neurosteroids are related to food intake control, the changes observed may be a novel mechanism in the regulation of energy balance in obese phytoestrogen-deprived animals. In rats, steroidogenesis and ER signaling appear to be altered by phytoestrogen withdrawal in the rat. The ubiquity of phytoestrogens in the diet and changing intakes or withdrawal suggest that aspects of human health could be affected based on the rat and warrant further research.

  14. Effects of feeding dairy cows different legume-grass silages on milk phytoestrogen concentration.

    PubMed

    Höjer, A; Adler, S; Purup, S; Hansen-Møller, J; Martinsson, K; Steinshamn, H; Gustavsson, A-M

    2012-08-01

    Phytoestrogens are hormone-like substances in plants that can substantially influence human health (positively or negatively), and when fed to dairy cows are partly transferred to their milk. The aim of this study was to investigate the effects of varying the botanical composition and regrowth interval of legume-grass silage on phytoestrogen intake and milk phytoestrogen concentrations. In one experiment, 15 Swedish Red dairy cows were fed 2- or 3-cut red clover-grass silage, or 2-cut birdsfoot trefoil-grass silage. In a second experiment, 16 Norwegian Red dairy cows were fed short-term ley silage with red clover or long-term ley silage with white clover, and the effects of supplementation with α-tocopherol were also tested. High concentrations of formononetin and biochanin A were found in all silage mixtures with red clover. The milk concentration of equol was highest for cows on the 2-cut red clover-grass silage diet (1,494 μg/kg of milk). Because of the metabolism of biochanin A, genistein, and prunetin, their concentrations in milk and the apparent recovery were low. Coumestrol was detected in only short-term and long-term ley silage mixtures, and its milk concentration was low. Concentrations of secoisolariciresinol and matairesinol were higher in 2-cut birdsfoot trefoil-grass and long-term ley silage mixtures, those with legume species other than red clover, and the highest grass proportions. The 2-cut birdsfoot trefoil-grass silage diet also resulted in higher enterolactone concentration than the other diets (226 μg/kg of milk). Lengthening the regrowth interval increased the intake of secoisolariciresinol and decreased the recovery of lignans. Feeding long-term ley silage resulted in higher milk lignan concentrations but lower milk isoflavone concentrations than feeding short-term ley silage. The apparent recovery of all phytoestrogens except prunetin was highest on the 2-cut birdsfoot trefoil-grass silage diet. No effect of α-tocopherol supplementation

  15. Phytoestrogens in Postmenopause: The State of the Art from a Chemical, Pharmacological and Regulatory Perspective

    PubMed Central

    Poluzzi, Elisabetta; Piccinni, Carlo; Raschi, Emanuel; Rampa, Angela; Recanatini, Maurizio; Ponti, Fabrizio De

    2014-01-01

    Phytoestrogens represent a diverse group of non-steroidal natural products, which seem to have some oestrogenic effects and are often marketed as food supplements. Population exposed to phytoestrogens is potentially increasing, in part because an unfavourable risk-benefit profile of Hormone Replacement Therapy (HRT) for prolonged treatments (e.g., osteoporosis prevention) highlighted by the publication of the Women Health Initiative (WHI) trial in 2002, but also because many post-menopausal women often perceived phytoestrogens in food supplements as a safer alternative than HRT. Despite of increasing preclinical and clinical studies in the past decade, appealing evidence is still lacking to support the overall positive risk-benefit profile of phytoestrogens. Their status as food supplements seems to discourage studies to obtain new evidence, and the chance to buy them by user’s initiative make it difficult to survey their prevalence and pattern of use. The aim of the present review is to: (a) outline the clinical scenario underlying the increased interest on phytoestrogens, by overviewing the evolution of the evidence on HRT and its main therapeutic goals (e.g., menopausal symptoms relief, chemoprevention, osteoporosis prevention); (b) address the chemical and pharmacological features (e.g. chemical structure, botanical sources, mechanism of action) of the main compounds (e.g., isoflavones, lignans, coumestans); (c) describe the clinical evidence on potential therapeutic applications; (d) put available evidence on their riskbenefit profile in a regulatory perspective, in light of the recent regulation on health claims of food supplements. PMID:24164197

  16. Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

    PubMed Central

    Chen, Xueyan; Uzuner, Ugur; Li, Man; Shi, Weibing; Yuan, Joshua S.; Dai, Susie Y.

    2016-01-01

    Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors. PMID:27589781

  17. Phytoestrogens in milk: Overestimations caused by contamination of the hydrolytic enzyme used during sample extraction.

    PubMed

    Bláhová, L; Kohoutek, J; Procházková, T; Prudíková, M; Bláha, L

    2016-09-01

    Isoflavones are natural phytoestrogens with antioxidant and endocrine-disrupting potencies. Monitoring of their levels is important to ensure the high quality and safety of food, milk, and dairy products. The efficiency and accuracy of phytoestrogen analyses in complex matrices such as milk depend on the extraction procedure, which often uses hydrolysis by means of the β-glucuronidase/sulfatase enzyme originating from Helix pomatia. The present study reveals that the commercially available hydrolytic enzyme is contaminated by several phytoestrogen isoflavones (genistein, daidzein, formononetin, and biochanin A) and their metabolite equol, as well as flavones (naringenin and apigenin) and coumestrol. We show that the concentrations of daidzein and genistein in the enzyme could have impaired the results of analyses of the main isoflavones in several previously published studies. Of 8 analyzed compounds, only equol was confirmed in the present study and it serves as a reliable marker of phytoestrogens originating from cow feed. Critical reassessment of phytoestrogen concentrations in milk is needed because several previously published studies might have overestimated the concentrations depending on the extraction procedure used. PMID:27394955

  18. Phytoestrogens in the environment, I: occurrence and exposure effects on fathead minnows.

    PubMed

    Rearick, Daniel C; Fleischhacker, Nathan T; Kelly, Megan M; Arnold, William A; Novak, Paige J; Schoenfuss, Heiko L

    2014-03-01

    Naturally occurring phytoestrogens may mimic biogenic estrogens and modulate endocrine action in vertebrates. Little is known, however, about their temporal and spatial variability in the environment and the biological effects associated with exposures. The present study assessed the environmental presence of phytoestrogens in human-impacted and relatively pristine areas. The response in larval and sexually mature fathead minnows to environmentally relevant concentrations of 3 common phytoestrogens (genistein, daidzein, and formononetin), both singly and in mixture, was also quantified. Phytoestrogens were only present in the human-impacted surface waters. When detected, mean concentrations were low (± standard deviation) in an urban lake: 1.4 ± 0.5 ng/L, 1.6 ± 0.7 ng/L, and 1.1 ± 0.2 ng/L for genistein, daidzein, and formononetin, respectively, and in treated wastewater effluent: 1.6 ± 0.4 ng/L, 1.8 ± 1.3 ng/L, and 2.0 ng/L. Biochanin A was detected twice, whereas zearalenone and coumestrol were never detected. No clear temporal trends of aqueous phytoestrogen concentration were evident. Larval survival was significantly reduced in genistein, formononetin, and mixture treatments, whereas adult male fish only exhibited subtle changes to their anatomy, physiology, and behavior. Daidzein-exposed adult females produced greater quantities of eggs. The present study indicates that genistein, daidzein, and formononetin are likely attenuated rapidly and are unlikely to cause widespread ecological harm in the absence of other stressors.

  19. Phytoestrogens and other botanicals: on the problems of evidence-based evaluation.

    PubMed

    Jargin, Sergei V

    2013-04-01

    Soy is the principal plant that produces phytoestrogens, named so because they bind to the estrogen receptors, however weakly compared to the estrogens. Recent reviews concluded that there is no convincing evidence in favor of alleviation of menopausal symptoms by phytoestrogens. However, some studies suggest their efficacy. The question is discussed here, whether vegetable analogues should be used for replacement therapy instead of physiological hormones, also because phytoestrogen preparations often contain a mixture of different components. There is a controversy: phytoestrogens are used to compensate for estrogen deficiency in menopause; but their estrogenic potential does not prevent from the use of soy in infant formulas and other foodstuffs. Feminizing effect of phytoestrogens and soy products may be subtle, detectable only in large populations. This matter should be clarified by independent research, which can be of importance for the future of soy in agriculture. Furthermore a tendency to present placebos and substances with unproven effects in the guise of evidence-based medications is discussed. In conclusion, research quality and possible influence by the industry should be taken into account defining inclusion criteria for studies into meta-analyses and reviews. The article presented patents discussion relevant to the article.

  20. Phytoestrogens in postmenopause: the state of the art from a chemical, pharmacological and regulatory perspective.

    PubMed

    Poluzzi, Elisabetta; Piccinni, Carlo; Raschi, Emanuel; Rampa, Angela; Recanatini, Maurizio; De Ponti, Fabrizio

    2014-01-01

    Phytoestrogens represent a diverse group of non-steroidal natural products, which seem to have some oestrogenic effects and are often marketed as food supplements. Population exposed to phytoestrogens is potentially increasing, in part because an unfavourable risk-benefit profile of Hormone Replacement Therapy (HRT) for prolonged treatments (e.g., osteoporosis prevention) highlighted by the publication of the Women Health Initiative (WHI) trial in 2002, but also because many post-menopausal women often perceived phytoestrogens in food supplements as a safer alternative than HRT. Despite of increasing preclinical and clinical studies in the past decade, appealing evidence is still lacking to support the overall positive risk-benefit profile of phytoestrogens. Their status as food supplements seems to discourage studies to obtain new evidence, and the chance to buy them by user's initiative make it difficult to survey their prevalence and pattern of use. The aim of the present review is to: (a) outline the clinical scenario underlying the increased interest on phytoestrogens, by overviewing the evolution of the evidence on HRT and its main therapeutic goals (e.g., menopausal symptoms relief, chemoprevention, osteoporosis prevention); (b) address the chemical and pharmacological features (e.g. chemical structure, botanical sources, mechanism of action) of the main compounds (e.g., isoflavones, lignans, coumestans); (c) describe the clinical evidence on potential therapeutic applications; (d) put available evidence on their riskbenefit profile in a regulatory perspective, in light of the recent regulation on health claims of food supplements.

  1. Multiple phytoestrogens inhibit cell growth and confer cytoprotection by inducing manganese superoxide dismutase expression.

    PubMed

    Robb, Ellen L; Stuart, Jeffrey A

    2014-01-01

    Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. As data on phytoestrogens continues to accumulate, it is clear that there is significant overlap in the cellular effects elicited by these various compounds. Here, we show that one mechanism by which a number of phytoestrogens achieve their growth inhibitory and cytoprotective effects is via induction of the mitochondrial manganese superoxide dismutase (MnSOD). Eight phytoestrogens, including resveratrol, coumestrol, kaempferol, genistein, daidzein, apigenin, isoliquirtigenin and glycitin, were tested for their ability to induce MnSOD expression in mouse C2C12 and primary myoblasts. Five of these, resveratrol, coumestrol, kaempferol, genistein and daidzein, significantly increased MnSOD expression, slowed proliferative growth and enhanced stress resistance (hydrogen peroxide LD50) . When siRNA was used to prevent the MnSOD induction by genistein, coumestrol or daidzein, none of these compounds exerted any effect on proliferative growth, and only the effect of coumestrol on stress resistance persisted. The estrogen antagonist ICI182780 prevented the increased MnSOD expression and also the changes in cell growth and stress resistance, indicating that these effects are mediated by estrogen receptors (ER). The absence of effects of resveratrol or coumestrol, but not genistein, in ERβ-null cells further indicated that this ER in particular is important in mediating these effects. Thus, an ER-mediated induction of MnSOD expression appears to underlie the growth inhibitory and cytoprotective activities of multiple phytoestrogens.

  2. Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α.

    PubMed

    Chen, Xueyan; Uzuner, Ugur; Li, Man; Shi, Weibing; Yuan, Joshua S; Dai, Susie Y

    2016-01-01

    Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER) and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD) when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX) assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors. PMID:27589781

  3. Phytoestrogens in milk: Overestimations caused by contamination of the hydrolytic enzyme used during sample extraction.

    PubMed

    Bláhová, L; Kohoutek, J; Procházková, T; Prudíková, M; Bláha, L

    2016-09-01

    Isoflavones are natural phytoestrogens with antioxidant and endocrine-disrupting potencies. Monitoring of their levels is important to ensure the high quality and safety of food, milk, and dairy products. The efficiency and accuracy of phytoestrogen analyses in complex matrices such as milk depend on the extraction procedure, which often uses hydrolysis by means of the β-glucuronidase/sulfatase enzyme originating from Helix pomatia. The present study reveals that the commercially available hydrolytic enzyme is contaminated by several phytoestrogen isoflavones (genistein, daidzein, formononetin, and biochanin A) and their metabolite equol, as well as flavones (naringenin and apigenin) and coumestrol. We show that the concentrations of daidzein and genistein in the enzyme could have impaired the results of analyses of the main isoflavones in several previously published studies. Of 8 analyzed compounds, only equol was confirmed in the present study and it serves as a reliable marker of phytoestrogens originating from cow feed. Critical reassessment of phytoestrogen concentrations in milk is needed because several previously published studies might have overestimated the concentrations depending on the extraction procedure used.

  4. Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

    PubMed

    Soni, M; White, L R; Kridawati, A; Bandelow, S; Hogervorst, E

    2016-06-01

    It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined. PMID:26535810

  5. Phytoestrogen consumption and risk for cognitive decline and dementia: With consideration of thyroid status and other possible mediators.

    PubMed

    Soni, M; White, L R; Kridawati, A; Bandelow, S; Hogervorst, E

    2016-06-01

    It is predicted that around 20% of the worlds population will be age 60 or above by 2050. Prevalence of cognitive decline and dementia is high in older adults and modifiable dietary factors may be able to reduce risk for these conditions. Phytoestrogens are bioactive plant chemicals found in soy, which have a similarity in structure to natural estradiol (the most abundant circulating estrogen). This structural likeness enables phytoestrogens to interact with estrogen receptors in the brain, potentially affecting cognition. However, findings in this domain are largely inconsistent, with approximately 50% of studies showing positive effects of phytoestrogens on cognition and the other half resulting in null/negative findings. This paper provides an updated review of the relationship between consumption of phytoestrogens and risk for cognitive decline and/or dementia. In particular, possible mediators were identified to explain discrepant findings and for consideration in future research. A case can be made for a link between phytoestrogen consumption, thyroid status and cognition in older age, although current findings in this area are very limited. Evidence suggests that inter-individual variants that can affect phytoestrogen bioavailability (and thus cognitive outcome) include age and ability to breakdown ingested phytoestrogens into their bioactive metabolites. Factors of the study design that must be taken into account are type of soy product, dosage, frequency of dietary intake and type of cognitive test used. Guidelines regarding optimal phytoestrogen dosage and frequency of intake are yet to be determined.

  6. Aquatic photochemistry of isoflavone phytoestrogens: degradation kinetics and pathways.

    PubMed

    Felcyn, Jacob R; Davis, Jasmine C C; Tran, Loan H; Berude, John C; Latch, Douglas E

    2012-06-19

    Isoflavones are plant-derived chemicals that are potential endocrine disruptors. Although some recent studies have detected isoflavones in natural waters, little is known about their aquatic fates. The photochemical behaviors of the isoflavones daidzein, formononetin, biochanin A, genistein, and equol were studied under simulated solar light and natural sunlight. All of these phytoestrogens were found to be photolabile under certain conditions. Daidzein and formononetin degraded primarily by direct photolysis. Their expected near-surface summer half-lives in pH 7 water at 47° latitude are expected to be 10 and 4.6 h, respectively. Biochanin A, genistein, and equol degraded relatively slowly by direct photolysis at environmentally realistic pH values, though they showed significant degradation rate enhancements in the presence of natural organic matter (NOM). The indirect photolysis rates for these compounds scaled with NOM concentration, and NOM from microbial origin was found to be a more potent photosensitizer than NOM from terrestrial sources. Mechanistic studies were performed to determine the indirect photolysis pathways responsible for the rate enhancements. Results of these studies implicate reaction with both singlet oxygen and excited state triplet NOM. Environmental half-lives for biochanin A, genistein, and equol are expected to vary on the basis of pH as well as NOM source and concentration.

  7. Phytoestrogens: epidemiology and a possible role in cancer protection.

    PubMed Central

    Adlercreutz, H

    1995-01-01

    Because many diseases of the Western Hemisphere are hormone-dependent cancers, we have postulated that the Western diet, compared to a vegetarian or semivegetarian diet, may alter hormone production, metabolism, or action at the cellular level by some biochemical mechanisms. Recently, our interest has been mainly focused on the cancer-protective role of some hormonelike diphenolic phytoestrogens of dietary origin, the lignans and the isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids), whole grain cereal food, seeds, and probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormonelike compounds with weak estrogenic but also antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, and angiogenesis in a way that makes them strong candidates for a role as natural cancer-protective compounds. Epidemiologic investigations strongly support this hypothesis because the highest levels of these compounds in the diet are found in countries or regions with low cancer incidence. This report is a review on recent results suggesting that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds. PMID:8593855

  8. Differential proteomic profile of spermatogenic and Sertoli cells from peri-pubertal testes of three different bovine breeds

    PubMed Central

    Tripathi, Utkarsh K.; Aslam, Muhammad K. M.; Pandey, Shashank; Nayak, Samiksha; Chhillar, Shivani; Srinivasan, A.; Mohanty, T. K.; Kadam, Prashant H.; Chauhan, M. S.; Yadav, Savita; Kumaresan, Arumugam

    2014-01-01

    Sub-fertility is one of the most common problems observed in crossbred males, but the etiology remains unknown in most of the cases. Although proteomic differences in the spermatozoa and seminal plasma between breeds have been investigated, the possible differences at the sperm precursor cells and supporting/nourishing cells have not been studied. The present study reports the differential proteomic profile of spermatogenic and Sertoli cells in crossbred and purebred bulls. Testis was removed by unilateral castration of 12 peri-pubertal bulls (10 months age), four each from crossbred (Holstein Friesian × Tharparkar), exotic purebred [Holstein Friesian (HF)] and indigenous purebred [Tharparkar (TP)] bulls. Spermatogenic and Sertoli cells were isolated and subjected to proteomic analysis. Protein extracts from the Sertoli and spermatogenic cells of each breed were analyzed with 2-dimensional difference gel electrophoresis (2D-DIGE) and analyzed with Decyder™ software. Compared to HF, 26 protein spots were over expressed and 14 protein spots were under expressed in spermatogenic cells of crossbred bulls. Similarly, 7 protein spots were over expressed and 15 protein spots were under expressed in the spermatogenic cells of TP bulls compared to that of crossbred bulls. Out of 12 selected protein spots identified through mass spectrometry, Phosphatidyl ethanolamine binding protein was found to be over expressed in the spermatogenic cells of crossbred bulls compared to TP bulls. The protein, gamma actin was found to be over expressed in the Sertoli cells of HF bulls, whereas Speedy Protein-A was found to be over expressed in Sertoli cells of crossbred bulls. It may be concluded that certain proteomic level differences exist in sperm precursor cells and nourishing cells between breeds, which might be associated with differences in the fertility among these breeds. PMID:25364731

  9. Effect of phytoestrogens on basal and GnRH-induced gonadotropin secretion.

    PubMed

    Arispe, Sergio A; Adams, Betty; Adams, Thomas E

    2013-12-01

    Plant-derived estrogens (phytoestrogens, PEs), like endogenous estrogens, affect a diverse array of tissues, including the bone, uterus, mammary gland, and components of the neural and cardiovascular systems. We hypothesized that PEs act directly at pituitary loci to attenuate basal FSH secretion and increase gonadotrope sensitivity to GnRH. To examine the effect of PEs on basal secretion and total production of FSH, ovine pituitary cells were incubated with PEs for 48 h. Conditioned media and cell extract were collected and assayed for FSH. Estradiol (E₂) and some PEs significantly decreased basal secretion of FSH. The most potent PEs in this regard were coumestrol (CM), zearalenone (ZR), and genistein (GN). The specificity of PE-induced suppression of basal FSH was indicated by the absence of suppression in cells coincubated with PEs and an estrogen receptor (ER) blocker (ICI 182 780; ICI). Secretion of LH during stimulation by a GnRH agonist (GnRH-A) was used as a measure of gonadotrope responsiveness. Incubation of cells for 12 h with E₂, CM, ZR, GN, or daidzein (DZ) enhanced the magnitude and sensitivity of LH secretion during subsequent exposure to graded levels of a GnRH-A. The E₂- and PE-dependent augmentation of gonadotrope responsiveness was nearly fully blocked during coincubation with ICI. Collectively, these data demonstrate that selected PEs (CM, ZR, and GN), like E₂, decrease basal secretion of FSH, reduce total FSH production, and enhance GnRH-A-induced LH secretion in a manner that is dependent on the ER. PMID:24050980

  10. Effect of phytoestrogens on basal and GnRH-induced gonadotropin secretion.

    PubMed

    Arispe, Sergio A; Adams, Betty; Adams, Thomas E

    2013-12-01

    Plant-derived estrogens (phytoestrogens, PEs), like endogenous estrogens, affect a diverse array of tissues, including the bone, uterus, mammary gland, and components of the neural and cardiovascular systems. We hypothesized that PEs act directly at pituitary loci to attenuate basal FSH secretion and increase gonadotrope sensitivity to GnRH. To examine the effect of PEs on basal secretion and total production of FSH, ovine pituitary cells were incubated with PEs for 48 h. Conditioned media and cell extract were collected and assayed for FSH. Estradiol (E₂) and some PEs significantly decreased basal secretion of FSH. The most potent PEs in this regard were coumestrol (CM), zearalenone (ZR), and genistein (GN). The specificity of PE-induced suppression of basal FSH was indicated by the absence of suppression in cells coincubated with PEs and an estrogen receptor (ER) blocker (ICI 182 780; ICI). Secretion of LH during stimulation by a GnRH agonist (GnRH-A) was used as a measure of gonadotrope responsiveness. Incubation of cells for 12 h with E₂, CM, ZR, GN, or daidzein (DZ) enhanced the magnitude and sensitivity of LH secretion during subsequent exposure to graded levels of a GnRH-A. The E₂- and PE-dependent augmentation of gonadotrope responsiveness was nearly fully blocked during coincubation with ICI. Collectively, these data demonstrate that selected PEs (CM, ZR, and GN), like E₂, decrease basal secretion of FSH, reduce total FSH production, and enhance GnRH-A-induced LH secretion in a manner that is dependent on the ER.

  11. Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats.

    PubMed

    Medigović, Ivana M; Živanović, Jasmina B; Ajdžanović, Vladimir Z; Nikolić-Kokić, Aleksandra L; Stanković, Sanja D; Trifunović, Svetlana L; Milošević, Verica Lj; Nestorović, Nataša M

    2015-12-01

    The aim of this study was to assess the effects of genistein (G) and daidzein (D) on the histological, hormonal, and functional parameters of the pituitary-ovarian axis in middle-aged female rats, and to compare these effects with the effects of estradiol (E), commonly used in the prevention and treatment of menopausal symptoms. Middle-aged (12 month old) Wistar female rats subcutaneously received 35 mg/kg of G, or 35 mg/kg of D, or 0.625 mg/kg of E every day for 4 weeks. Each of the treated groups had a corresponding control group. An intact control group was also established. G and D did not change the intracellular protein content within gonadotropic and lactotropic cells, but vacuolization was observed in all the cell types. In contrast, E caused an inhibition of gonadotropic and stimulation of lactotropic cells. Also, ovaries of middle-aged female rats exposed to G or D have more healthy primordial and primary follicles and less atretic follicles. E treatment in the ovaries had a mostly negative effect, which is reflected by the increased number of atretic follicles in all tested classes. G and D provoked decrease in CuZnSOD and CAT activity, while E treatment increased MnSOD and decreased CuZnSOD and GSHPx activity. All the treatments increased serum estradiol and decreased testosterone levels, while D and E increased the serum progesterone level. In conclusion, soy phytoestrogens exhibited beneficial effects on pituitary-ovarian function in middle-aged female rats, as compared to estradiol.

  12. Soya phytoestrogens change cortical and hippocampal expression of BDNF mRNA in male rats.

    PubMed

    File, Sandra E; Hartley, David E; Alom, Nazmul; Rattray, Marcus

    2003-02-27

    Adult male hooded Lister rats were either fed a diet containing 150 microg/g soya phytoestrogens or a soya-free diet for 18 days. This concentration of phytoestrogens should have been sufficient to occupy the oestrogen-beta, but not the oestrogen-alpha, receptors. Using in situ hybridisation, significant reductions were found in brain-derived neurotrophic factor (BDNF) mRNA expression in the CA3 and CA4 region of the hippocampus and in the cerebral cortex in the rats fed the diet containing phytoestrogens, compared with those on the soya-free diet. No changes in glutamic acid decarboxylase-67 or glial fibrillary acidic protein mRNA were found. This suggests a role for oestrogen-beta receptors in regulating BDNF mRNA expression.

  13. Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis

    PubMed Central

    Lee, Geum-A.; Hwang, Kyung-A.; Choi, Kyung-Chul

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy. PMID:27231938

  14. Hormonal action of plant derived and anthropogenic non-steroidal estrogenic compounds: phytoestrogens and xenoestrogens.

    PubMed

    Lóránd, T; Vigh, E; Garai, J

    2010-01-01

    Herbivorous and omnivorous vertebrates have evolved in the presence of a variety of phytoestrogens, i.e., plant-derived compounds that can mimic, modulate or disrupt the actions of endogenous estrogens. Since the discovery of the estrus-inducing effects of some plant products in 1926, considerable effort has been devoted to the isolation and structural and pharmacological characterization of phytoestrogens. Recently, agricultural and industrial pollution has added anthropogenic estrogenic compounds to the list of environmental estrogens. Unlike phytoestrogens, these xenoestrogens tend to accumulate and persist in adipose tissue for decades and may cause long-lasting, adverse endocrine effects. Here we review the endocrine effects of known phytoestrogens and xenoestrogens with special emphasis on molecular structure-activity relationships. Phytoestrogens include flavonoids, isoflavonoids, chalcons, coumestans, stilbenes, lignans, ginsenosides and other saponins, as well as the recently discovered tetrahydrofurandiols. Fungal estrogenic compounds may enter the food chain via infested crops. Since some phytoestrogens have been shown to display organ-specific actions, pharmaceutical estrogen analogues with similar properties (selective estrogen receptor modulators, SERMs) are also discussed. Xenoestrogens include dichlorodiphenyltrichloroethane (DDT) and its metabolites, bisphenols, alkylphenols, dichlorophenols, methoxychlor, chlordecone, polychlorinated benzol derivatives (PCBs), and dioxins. While most of these compounds act through estrogen receptors alpha and beta, some of their effects may be mediated by other nuclear or membrane-bound receptors or receptor-independent mechanisms. Some might also interfere with the production and metabolism of ovarian estrogens. Better understanding of the molecular pharmacology of phyto- and xenoestrogens may result in the development of novel compounds with therapeutic utility and improved environmental protection.

  15. Reproductive consequences of exposure to waterborne phytoestrogens in male fighting fish Betta splendens.

    PubMed

    Stevenson, Louise M; Brown, Alexandria C; Montgomery, Tracy M; Clotfelter, Ethan D

    2011-04-01

    Phytoestrogens are plant compounds that can act as endocrine disruptors in vertebrates. Biologically active levels of phytoestrogens have been found in aquatic habitats near wood pulp and paper mills, biofuel manufacturing plants, sewage-treatment plants, and agricultural fields. Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success. In one experiment, we exposed sexually mature male fighting fish Betta splendens to environmentally relevant (1 μg L(-1)) and pharmacological concentrations (1000 μg L(-1)) of the phytoestrogen genistein as well as to a positive control of waterborne 17β-estradiol (E2; 1 μg L(-1)), and a negative control of untreated water. In a second experiment, we exposed male B. splendens to environmentally relevant concentrations (1 μg L(-1)) of genistein and β-sitosterol singly and in combination as well as to the positive and negative controls. All exposures were 21 days in duration. We measured sex-steroid hormone levels, gonadosomatic index (GSI), sperm concentration and motility, and fertilization success in these fish. We found that exposure to genistein did not affect circulating levels of the androgen 11-ketotestosterone or the estrogen E2 relative to negative-control fish. We also found that neither of the compounds nor their mixture affected GSI, sperm concentration or motility, or fertilization success in exposed fish relative to negative-control fish. However, fish exposed to phytoestrogens showed some evidence of fewer but more motile sperm than fish exposed to the positive control E2. We conclude that sexually mature male B. splendens are relatively immune to reproductive impairments from short-term exposure to waterborne phytoestrogens.

  16. Reproductive consequences of exposure to waterborne phytoestrogens in male fighting fish Betta splendens.

    PubMed

    Stevenson, Louise M; Brown, Alexandria C; Montgomery, Tracy M; Clotfelter, Ethan D

    2011-04-01

    Phytoestrogens are plant compounds that can act as endocrine disruptors in vertebrates. Biologically active levels of phytoestrogens have been found in aquatic habitats near wood pulp and paper mills, biofuel manufacturing plants, sewage-treatment plants, and agricultural fields. Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success. In one experiment, we exposed sexually mature male fighting fish Betta splendens to environmentally relevant (1 μg L(-1)) and pharmacological concentrations (1000 μg L(-1)) of the phytoestrogen genistein as well as to a positive control of waterborne 17β-estradiol (E2; 1 μg L(-1)), and a negative control of untreated water. In a second experiment, we exposed male B. splendens to environmentally relevant concentrations (1 μg L(-1)) of genistein and β-sitosterol singly and in combination as well as to the positive and negative controls. All exposures were 21 days in duration. We measured sex-steroid hormone levels, gonadosomatic index (GSI), sperm concentration and motility, and fertilization success in these fish. We found that exposure to genistein did not affect circulating levels of the androgen 11-ketotestosterone or the estrogen E2 relative to negative-control fish. We also found that neither of the compounds nor their mixture affected GSI, sperm concentration or motility, or fertilization success in exposed fish relative to negative-control fish. However, fish exposed to phytoestrogens showed some evidence of fewer but more motile sperm than fish exposed to the positive control E2. We conclude that sexually mature male B. splendens are relatively immune to reproductive impairments from short-term exposure to waterborne phytoestrogens. PMID:20589370

  17. In vitro and in vivo effects of phytoestrogens on protein turnover in rainbow trout (Oncorhynchus mykiss) white muscle.

    PubMed

    Cleveland, Beth M

    2014-09-01

    Soybeans and other legumes investigated as fishmeal replacements in aquafeeds contain phytoestrogens capable of binding to and activating estrogen receptors. Estradiol has catabolic effects in salmonid white muscle, partially through increases in protein turnover. The current study determines whether phytoestrogens promote similar effects. In rainbow trout (Oncorhynchus mykiss) primary myocyte cultures, the phytoestrogens genistein, daidzein, glycitein, and R- and S-equol reduced rates of protein synthesis and genistein, the phytoestrogen of greatest abundance in soy, also increased rates of protein degradation. Increased expression of the ubiquitin ligase fbxo32 and autophagy-related genes was observed with high concentrations of genistein (100 μM), and R- and S-equol (100 μM) also up-regulated autophagy-related genes. In contrast, low genistein concentrations in vitro (0.01-0.10 μM) and in vivo (5 μg/g body mass) decreased fbxo32 expression, suggesting a potential metabolic benefit for low levels of genistein exposure. Phytoestrogens reduced cell proliferation, indicating that effects of phytoestrogens extend from metabolic to mitogenic processes. Co-incubation of genistein with the estrogen receptor (ER) antagonist, ICI 182,780, ameliorated effects of genistein on protein degradation, but not protein synthesis or cell proliferation, indicating that effects of genistein are mediated through ER-dependent and ER-independent mechanisms. Collectively, these data warrant additional studies to determine the extent to which dietary phytoestrogens, especially genistein, affect physiological processes that impact growth and nutrient retention.

  18. The Stimulatory Effect of Strontium Ions on Phytoestrogens Content in Glycine max (L.) Merr.

    PubMed

    Wójciak-Kosior, Magdalena; Sowa, Ireneusz; Blicharski, Tomasz; Strzemski, Maciej; Dresler, Sławomir; Szymczak, Grażyna; Wnorowski, Artur; Kocjan, Ryszard; Świeboda, Ryszard

    2016-01-14

    The amount of secondary metabolites in plants can be enhanced or reduced by various external factors. In this study, the effect of strontium ions on the production of phytoestrogens in soybeans was investigated. The plants were treated with Hoagland's solution, modified with Sr(2+) with concentrations ranging from 0.5 to 3.0 mM, and were grown for 14 days in hydroponic cultivation. After harvest, soybean plants were separated into roots and shoots, dried, and pulverized. The plant material was extracted with methanol and hydrolyzed. Phytoestrogens were quantified by HPLC. The significant increase in the concentration of the compounds of interest was observed for all tested concentrations of strontium ions when compared to control. Sr(2+) at a concentration of 2 mM was the strongest elicitor, and the amount of phytoestrogens in plant increased ca. 2.70, 1.92, 3.77 and 2.88-fold, for daidzein, coumestrol, genistein and formononetin, respectively. Moreover, no cytotoxic effects were observed in HepG2 liver cell models after treatment with extracts from 2 mM Sr(2+)-stressed soybean plants when compared to extracts from non-stressed plants. Our results indicate that the addition of strontium ions to the culture media may be used to functionalize soybean plants with enhanced phytoestrogen content.

  19. Phytoestrogens alter the reproductive organ development in the mink (Mustela vison)

    SciTech Connect

    Ryoekkynen, Ari . E-mail: ryokkyne@cc.joensuu.fi; Nieminen, Petteri; Mustonen, Anne-Mari; Pyykoenen, Teija; Asikainen, Juha; Haenninen, Sari; Mononen, Jaakko; Kukkonen, Jussi V.K.

    2005-01-15

    The aim of the present study was to examine the reproductive effects of two perorally applied phytoestrogens, genistein (8 mg/kg/day) and {beta}-sitosterol (50 mg/kg/day), on the mink (Mustela vison) at human dietary exposure levels. Parental generations were exposed over 9 months to these phytoestrogens and their offspring were exposed via gestation and lactation. Parents and their offspring were sampled 21 days after the birth of the kits. Sex hormone levels, sperm quality, organ weights, and development of the kits were examined. The exposed females were heavier than the control females at the 1st postnatal day (PND). The control kits were heavier than the exposed kits from the 1st to the 21st PND. Phytoestrogens did not affect the organ weights of the adult minks, but the relative testicular weight of the exposed kits was higher than in the control kits. The relative prostate weight was higher and the relative uterine weight lower in the {beta}-sitosterol-exposed kits than in the control kits. Moreover, the plasma dihydrotestosterone levels were lower in the genistein-exposed male kits compared to the control male kits. This study could not explain the mechanisms behind these alterations. The results indicate that perinatal phytoestrogen exposures cause alterations in the weight of the reproductive organs of the mink kits.

  20. Effects of phytoestrogens on indices of protein turnover in rainbow trout (Oncorhynchus mykiss) primary myocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybeans and other legumes investigated as alternative ingredients in aquafeeds contain phytoestrogens that act as endocrine disruptors, capable of binding to and activating estrogen receptors, although at a much lower level of estrogenicity compared to estradiol. Estradiol has catabolic effects on...

  1. Effects of phytoestrogens on protein turnover in rainbow trout primary myocytes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean-derived ingredients used in aquaculture feeds may contain phytoestrogens, but it is unknown if these compounds can mimic the catabolic effects of estradiol in fish muscle. Six day-old rainbow trout primary myocytes were exposed to increasing concentrations (10 nM – 100 µM) of either geniste...

  2. Urinary phytoestrogens in relation to metabolic disturbances among children and adolescents.

    PubMed

    Jeng, Hueiwang Anna C; Kantaria, Khyati; Beydoun, Hind A

    2015-01-01

    Previous studies have examined whether phytoestrogens affect glucose and lipid metabolism. However, data on children and adolescents are still limited, with most of the evidence pertaining to one phytoestrogen, namely genistein. To investigate the effect of six phytoestrogens [daidezin, enterodiol, enterolactone, equol, genistein and O-Desmethylangolensin (O-DMA)] on metabolic disturbances among youths, a cross-sectional study was conducted using a sample of 2,429 children and adolescents, 6-18 years, from the 2009-2010 National Health and Nutrition Examination Surveys (NHANES). The main outcome measures were body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and total cholesterol (TC), fasting glucose, triglycerides and glycohemoglobin. SBP was inversely related to enterolactone and equol. Triglycerides were inversely related to daidezin, equol, genistein and O-DMA. Whereas TC and LDL-C were inversely related to equol, an HDL-C was inversely related to genistein and O-DMA. Whereas fasting glucose was associated with enterodiol (β = 0.33, 95% CI: 0.028, 0.63), a positive relationship was observed between enterodiol and risk of HDL-C ≥ 35 mg dl(-1) (β = 0.04, 95% CI: 0.01, 0.07). In conclusion, certain phytoestrogens may contribute either positively or negatively to disturbances in lipid and glucose metabolism. Large prospective cohort studies are needed to confirm our study findings.

  3. Effects of phytoestrogens on growth-related and lipogenic genes in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the current study was to determine whether estradiol (E2) or the primary soy phytoestrogens genistein and daidzein regulate expression of growth-related and lipogenic genes in rainbow trout. Juvenile rainbow trout (5 mon, 65.8 ± 1.8 g) received intraperitoneal injections of E2, gen...

  4. Phytoestrogens levels determination in the cord blood from Malaysia rural and urban populations

    SciTech Connect

    Mustafa, A.M. . E-mail: mustafa@ummc.edu.my; Malintan, N.T.; Seelan, S.; Zhan, Z.; Mohamed, Z.; Hassan, J.; Pendek, R.; Hussain, R.; Ito, N.

    2007-07-01

    This study is a result of an analysis of free and conjugated phytoestrogens daidzein, genistein, daidzin, genistin and coumesterol in human cord blood plasma using LCMS. Cord blood was collected from urban and rural populations of Malaysia (n = 300) to establish a simple preliminary database on the levels of the analyzed compounds in the collected samples. The study also aimed to look at the levels of phytoestrogens in babies during birth as this may have a profound effect on the developmental process. The sample clean up was carried out by solid-phase extraction using C18 column and passed through DEAE sephadex gel before analysis by LCMS. The mean concentrations of total phytoestrogens were daidzein (1.4 {+-} 2.9 ng/ml), genistein (3.7 {+-} 2.8 ng/ml), daidzin (3.5 {+-} 3.1 ng/ml), genistin (19.5 {+-} 4.2 ng/ml) and coumesterol (3.3 {+-} 3.3 ng/ml). Distribution of phytoestrogen was found to be higher in samples collected from rural areas compared to that of urban areas.

  5. Genome-wide DNA methylation modified by soy phytoestrogens: role for epigenetic therapeutics in prostate cancer?

    PubMed

    Karsli-Ceppioglu, Seher; Ngollo, Marjolaine; Adjakly, Mawussi; Dagdemir, Aslihan; Judes, Gaëlle; Lebert, André; Boiteux, Jean-Paul; Penault-LLorca, Frédérique; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2015-04-01

    In prostate cancer, DNA methylation is significantly associated with tumor initiation, progression, and metastasis. Previous studies have suggested that soy phytoestrogens might regulate DNA methylation at individual candidate gene loci and that they play a crucial role as potential therapeutic agents for prostate cancer. The purpose of our study was to examine the modulation effects of phytoestrogens on a genome-wide scale in regards to DNA methylation in prostate cancer. Prostate cancer cell lines DU-145 and LNCaP were treated with 40 μM of genistein and 110 μM of daidzein. DNMT inhibitor 5-azacytidine (2 μM) and the methylating agent budesonide (2 μM) were used to compare their demethylation/methylation effects with phytoestrogens. The regulatory effects of phytoestrogens on DNA methylation were analyzed by using a methyl-DNA immunoprecipitation method coupled with Human DNA Methylation Microarrays (MeDIP-chip). We observed that the methylation profiles of 58 genes were altered by genistein and daidzein treatments in DU-145 and LNCaP prostate cancer cells. In addition, the methylation frequencies of the MAD1L1, TRAF7, KDM4B, and hTERT genes were remarkably modified by genistein treatment. Our results suggest that the modulation effects of phytoestrogens on DNA methylation essentially lead to inhibition of cell growth and induction of apoptosis. Genome-wide methylation profiling reported here suggests that epigenetic regulation mechanisms and, by extension, epigenetics-driven novel therapeutic candidates warrant further consideration in future "omics" studies of prostate cancer.

  6. Effects of estrogen and phytoestrogens on endometrial leakage in ovariectomized rats and the related mechanisms.

    PubMed

    Li, Hong-Fang; Duan, Ying; Wang, Long-De; Tian, Zhi-Feng; Qiu, Xiao-Qing; Zhang, Ying-Fu; Zhang, Hua; Yang, Li-Na

    2013-02-25

    Phytoestrogens, a group of plant-derived non-steroidal compounds that can behave as estrogens by binding to estrogen receptors, have drawn great attention for their potentially beneficial effects on human health. However, there are few studies investigating the potential side effects of phytoestrogens on the reproductive system. The present study was to elucidate the effects of 17β-estradiol (E2), progesterone (P4), and phytoestrogens genistein (Gen), resveratrol (Res), and phloretin (Phl) on eosinophilic infiltration of the ovariectomized rat uterus and endometrial vascular permeability, and to analyze the underlying mechanisms. The ovariectomized rats received daily subcutaneous injections of E2, E2+P4, P4, Gen, Res, Phl, or an equivalent volume of vehicle for 21 days, and sham-operated animals (Sham rats) were used as the controls. Hematoxylin-eosin staining revealed a marked increase in uterine eosinophilic infiltrations in ovariectomized rats treated with E2, E2+P4 or P4, which was associated with increased expression of vascular endothelial growth factor (VEGF), nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α) proteins as determined by immunohistochemical and Western blot analysis. However, all three phytoestrogens had no markedly effect on the uterine eosinophilic infiltration and the expressions of VEGF, NF-κB, and TNF-α in the uterus of ovariectomized rats. Our data demonstrate that E2 alone or in combination with P4 increases uterine eosinophilic infiltration which is related with vascular hyperpermeability caused by VEGF, NF-κB and TNF-α, whereas phytoestrogens Gen, Res, and Phl, have no such an effect.

  7. Dracaena arborea alleviates ultra-structural spermatogenic alterations in streptozotocin-induced diabetic rats

    PubMed Central

    2013-01-01

    Background Infertility is a common complication in diabetic men and experimental animals, mainly due to loss of germ cells by apoptotic cell death. The aim of this study was to evaluate the effects of aqueous and ethanol extracts of Dracaena arborea in streptozotocin-induced ultra-structural spermatogenic alterations in Wistar rats. Methods Diabetic animals were orally treated with Millipore water (10 ml/kg), sildenafil citrate (1.44 mg/kg) or Dracaena arborea aqueous (500 mg/kg) and ethanol (100 mg/kg) extracts for three weeks. A group of non diabetic rats received Millipore water (10 ml/kg) and served as healthy control group. Blood glucose was monitored at the beginning and the end of the study. One day after the last treatment, animals were sacrificed and the testes immediately removed were morphologically observed and prepared for electron microscopy analysis of spermatogenesis. Results Our results showed that Dracaena arborea was devoid of any anti-hyperglycemic activity. In the untreated diabetic rats, hyperglycemia severely damaged the testes morphology as well as the spermatogenic process as evidenced by the: thickness of basement membrane of the seminiferous tubule; mitochondria alteration; abnormal spermatocyte cells displaying polymorphous nuclei, cytoplasmic vacuolization and necrosis; and disorganization and degeneration of sperm germ cells. Administration of sildenafil citrate and Dracaena arborea extracts to the diabetic rats improved testes morphology and reversed, although not completely, the impairment of spermatogenesis; this alleviating effect was more pronounced in animals treated with the aqueous extract (500 mg/kg) of Dracaena arborea. Conclusion Dracaena arborea improves testes morphology and restores spermatogenesis in type 1 diabetic rats, without having major anti-hyperglycemic properties. These effects could be attributed to saponins, flavonoids, phenols and sterols revealed in this plant, which could be a useful component

  8. BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

    PubMed

    Xu, Guogang; Vogel, Kristine S; McMahan, C Alex; Herbert, Damon C; Walter, Christi A

    2010-12-01

    During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

  9. Effect of Black maca (Lepidium meyenii) on one spermatogenic cycle in rats.

    PubMed

    Gonzales, G F; Nieto, J; Rubio, J; Gasco, M

    2006-10-01

    Lepidium meyenii (Maca) grows exclusively between 4000 and 4500 m above sea level in the Peruvian central Andes. The hypocotyls of this plant are traditionally used in the Andean region for their supposed fertility-enhancing properties. The hypocotyls have different colours. Of these, Black maca has better effects on spermatogenesis. The present study aimed to test the hypothesis that Black maca has early effects during a spermatogenic cycle (12 days) of male rats. For this, testicular spermatid, epididymal sperm and vas deferens sperm counts were measured after 1, 3, 5, 7 and 12 days of treatment with Black maca. Aqueous extract of Black maca was given orally by daily gavage at a dose of 2 g kg(-1). In a spermatogenic cycle, compared with day 1, daily sperm production (DSP) was lower at day 7 (control), whereas with Black maca, the difference was observed at day 12. Epididymal sperm count was higher in rats treated with Black maca at days 1, 3 and 7, but similar to controls at days 5 and 12; similarly sperm counts in vas deferens was higher in rats treated with Black maca in days 3, 5 and 7, but similar to controls at days 1 and 12. From this, it is suggested that first action of Black maca was at epididymal level increasing sperm count after 1 day of treatment, whereas an increase in sperm count was observed in vas deferens at day 3 of treatment. Finally, an increase in DSP was observed after 7 days of treatment with Black maca. Testicular testosterone was not affected after 7 days treatment with Black maca. In conclusion, Black maca affects sperm count as early as 1 day after beginning of treatment. PMID:16961569

  10. Tetrahydroisoquinoline alkaloids mimic direct but not receptor-mediated inhibitory effects of estrogens and phytoestrogens on testicular endocrine function. Possible significance for Leydig cell insufficiency in alcohol addiction

    SciTech Connect

    Stammel, W.; Thomas, H. ); Staib, W.; Kuehn-Velten, W.K. )

    1991-01-01

    Possible effects of various tetrahydroisoquinolines (TIQs) on rat testicular endocrine function were tested in vitro in order to prove whether these compounds may be mediators of the development of Leydig cell insufficiency. TIQ effects on different levels of regulation of testis function were compared in vitro with estrogen effects, since both classes of compounds have structural similarities. Gonadotropin-stimulated testosterone production by testicular Leydig cells was inhibited by tetrahydropapaveroline and isosalsoline, the IC{sub 50} values being comparable to those of estradiol, 2-hydroxyestradiol, and the phytoestrogens, coumestrol and genistein; salsolinol and salsoline were less effective, and salsolidine was ineffective. None of these TIQs interacted significantly with testicular estrogen receptor as analyzed by estradiol displacement. However, tetrahydropapaveroline, isosalsoline and salsolinol competitively inhibited substrate binding to cytochrome P45OXVII, with similar efficiency as the estrogens did; salsoline and salsolidine were again much less effective.

  11. Phytoestrogens β-Sitosterol and Genistein Have Limited Effects on Reproductive Endpoints in a Female Fish, Betta splendens

    PubMed Central

    Brown, A. C.; Stevenson, L. M.; Leonard, H. M.; Nieves-Puigdoller, K.; Clotfelter, E. D.

    2014-01-01

    Phytoestrogens are produced by plants and may cause endocrine disruption in vertebrates. The present study hypothesizes that phytoestrogen exposure of female Siamese fighting fish (Betta splendens) may disrupt endogenous steroid levels, change agonistic behavior expression, and potentially also disrupt oocyte development. However, only the pharmacologic dose of β-sitosterol had a significant effect on opercular flaring behavior, while we did not find significant effects of β-sitosterol or genistein on steroids or gonads. These findings are in direct contrast with previous studies on the effects of phytoestrogens in female fish. Results of the current study support previous work showing that the effects of phytoestrogen exposure may be less acute in mature female B. splendens than in other fish. PMID:24707495

  12. In vitro and in vivo effects of phytoestrogens on protein turnover in rainbow trout (Oncorhynchus mykiss) white muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybeans and other legumes investigated as fishmeal replacements in aquafeeds contain phytoestrogens capable of binding to and activating estrogen receptors. Estradiol has catabolic effects in salmonid white muscle, partially through increases in protein turnover. The current study determines whet...

  13. Phytoestrogens β -sitosterol and genistein have limited effects on reproductive endpoints in a female fish, Betta splendens.

    PubMed

    Brown, A C; Stevenson, L M; Leonard, H M; Nieves-Puigdoller, K; Clotfelter, E D

    2014-01-01

    Phytoestrogens are produced by plants and may cause endocrine disruption in vertebrates. The present study hypothesizes that phytoestrogen exposure of female Siamese fighting fish (Betta splendens) may disrupt endogenous steroid levels, change agonistic behavior expression, and potentially also disrupt oocyte development. However, only the pharmacologic dose of β-sitosterol had a significant effect on opercular flaring behavior, while we did not find significant effects of β-sitosterol or genistein on steroids or gonads. These findings are in direct contrast with previous studies on the effects of phytoestrogens in female fish. Results of the current study support previous work showing that the effects of phytoestrogen exposure may be less acute in mature female B. splendens than in other fish.

  14. Phytoestrogens β -sitosterol and genistein have limited effects on reproductive endpoints in a female fish, Betta splendens.

    PubMed

    Brown, A C; Stevenson, L M; Leonard, H M; Nieves-Puigdoller, K; Clotfelter, E D

    2014-01-01

    Phytoestrogens are produced by plants and may cause endocrine disruption in vertebrates. The present study hypothesizes that phytoestrogen exposure of female Siamese fighting fish (Betta splendens) may disrupt endogenous steroid levels, change agonistic behavior expression, and potentially also disrupt oocyte development. However, only the pharmacologic dose of β-sitosterol had a significant effect on opercular flaring behavior, while we did not find significant effects of β-sitosterol or genistein on steroids or gonads. These findings are in direct contrast with previous studies on the effects of phytoestrogens in female fish. Results of the current study support previous work showing that the effects of phytoestrogen exposure may be less acute in mature female B. splendens than in other fish. PMID:24707495

  15. Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats.

    PubMed

    Adaramoye, O A; Lawal, S O

    2014-10-01

    The antihyperglycaemic effect of kolaviron (KV), a biflavonoid from Garcinia kola has been established in previous studies. In this study, we investigated the effect of KV (200 mg kg(-1) ) on the antioxidant, hormonal and spermatogenic indices of alloxan-diabetic male rats, and metformin hydrochloride (MET) (30 mg kg(-1) ) served as standard drug. The results showed that KV and MET significantly (P < 0.05) decreased the fasting blood glucose of the diabetic rats. Also, untreated and MET-treated diabetic groups had significantly (P < 0.05) lower body-weight gain and relative weights of testes. In addition, epididymal sperm abnormalities were increased, whereas sperm count, motility, testicular protein and sialic acid were decreased in untreated diabetic group. Also, antioxidant parameters, reduced glutathione, catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase were significantly (P < 0.05) reduced in the testes with a concomitant increase in lipid peroxidation in untreated diabetic group. Furthermore, untreated diabetic group had significantly (P < 0.05) lower levels of testosterone, luteinising and follicle-stimulating hormones relative to controls. Treatment with KV restored the relative weights of testes, activities of antioxidant enzymes, sperm and hormonal indices of the diabetic animals. This study demonstrated the role of KV to promote fertility in diabetic male rats by enhancing the hormonal and antioxidant status of the rats.

  16. Phytoestrogens and their metabolites in bulk-tank milk: effects of farm management and season.

    PubMed

    Adler, Steffen A; Purup, Stig; Hansen-Møller, Jens; Thuen, Erling; Steinshamn, Håvard

    2015-01-01

    Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG) was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of phytoestrogens

  17. Phytoestrogens and their metabolites in bulk-tank milk: effects of farm management and season.

    PubMed

    Adler, Steffen A; Purup, Stig; Hansen-Møller, Jens; Thuen, Erling; Steinshamn, Håvard

    2015-01-01

    Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG) was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of phytoestrogens

  18. Phytoestrogens and Their Metabolites in Bulk-Tank Milk: Effects of Farm Management and Season

    PubMed Central

    Adler, Steffen A.; Purup, Stig; Hansen-Møller, Jens; Thuen, Erling; Steinshamn, Håvard

    2015-01-01

    Phytoestrogens have structures similar to endogenous steroids and may induce or inhibit the response of hormone receptors. The objectives of the present study were to compare the effects of long-term vs. short-term grassland management in organic and conventional dairy production systems, compare organic and conventional production systems and assess seasonal variation on phytoestrogen concentrations in bulk-tank milk. The concentrations of phytoestrogens were analyzed in bulk-tank milk sampled three times in two subsequent years from 28 dairy farms: Fourteen organic (ORG) dairy farms with either short-term or long-term grassland management were paired with 14 conventional (CON) farms with respect to grassland management. Grassland management varied in terms of time since establishment. Short-term grassland management (SG) was defined as establishment or reseeding every fourth year or more often, and long-term grassland management (LG) was defined as less frequent establishment or reseeding. The proportion of red clover (Trifolium pretense L.) in the herbage was positively correlated with milk concentrations of the mammalian isoflavone equol. Therefore, organically produced bulk-tank milk contained more equol than conventionally produced milk, and milk from ORG-SG farms had more equol than milk from ORG-LG farms. Milk produced during the indoor-feeding periods had more equol than milk produced during the outdoor feeding period, because pastures contained less red clover than fields intended for silage production. Organically produced milk had also higher concentrations of the mammalian lignan enterolactone, but in contrast to equol, concentrations increased in the outdoor-feeding periods compared to the indoor-feeding periods. There were no indications of fertility problems on ORG-SG farms who had the highest red clover proportions in the herbage. This study shows that production system, grassland management, and season affect milk concentrations of phytoestrogens

  19. Early-life exposure to benzo[a]pyrene increases mutant frequency in spermatogenic cells in adulthood.

    PubMed

    Xu, Guogang; McMahan, C Alex; Walter, Christi A

    2014-01-01

    Children are vulnerable to environmental mutagens, and the developing germline could also be affected. However, little is known about whether exposure to environmental mutagens in childhood will result in increased germline mutations in subsequent adult life. In the present study, male transgenic lacI mice at different ages (7, 25 and 60 days old) were treated with a known environmental mutagen (benzo[a]pyrene, B[a]P) at different doses (0, 50, 200 or 300 mg/kg body weight). Mutant frequency was then determined in a meiotic cell type (pachytene spermatocyte), a post-meiotic cell type (round spermatid) and epididymal spermatozoa after at least one cycle of spermatogenesis. Our results show that 1) mice treated with B[a]P at 7 or 25 days old, both being pre-adult ages, had significantly increased mutant frequencies in all spermatogenic cell types tested when they were 60 days old; 2) spermatogenic cells from mice treated before puberty were more susceptible to B[a]P-associated mutagenesis compared to adult mice; and 3) unexpectedly, epididymal spermatozoa had the highest mutant frequency among the spermatogenic cell types tested. These data show that pre-adult exposure to B[a]P increases the male germline mutant frequency in young adulthood. The data demonstrate that exposure to environmental genotoxins at different life phases (e.g., pre-adult and adult) can have differential effects on reproductive health.

  20. Breast cancer: mechanisms involved in action of phytoestrogens and epigenetic changes.

    PubMed

    Dagdemir, Aslihan; Durif, Julie; Ngollo, Marjolaine; Bignon, Yves-Jean; Bernard-Gallon, Dominique

    2013-01-01

    In this review, we consider phytoestrogens and different epigenetic modifications in breast cancer. Epigenetic phenomena are mediated by several molecular mechanisms comprising histone modifications, small non-coding or anti-sense RNA and DNA methylation. These different modifications are closely interrelated. De-regulation of gene expression is a hallmark of cancer. Although genetic lesions have been the focus of cancer research for many years, it has become increasingly recognized that aberrant epigenetic modifications also play major roles in breast carcinogenesis. The incidence and mortality rates of breast cancer are high in the Western world compared with countries in Asia. There are also differences in the breast cancer incidence rates in different Western countries. This could be related to phytoestrogens.

  1. Rapid analysis of phytoestrogens in human urine by time-resolved fluoroimmunoassay.

    PubMed

    Uehara, M; Lapcík, O; Hampl, R; Al-Maharik, N; Mäkelä, T; Wähälä, K; Mikola, H; Adlercreutz, H

    2000-04-01

    A time-resolved fluoroimmunoassay (TR-FIA), with europium labeled phytoestrogens as tracers, was developed for the quantitative determination of enterolactone, genistein and daidzein in human urine. The aim was to create a method for the screening of large populations in order to assess the possible correlations between the urinary levels and the risk of Western diseases. After the synthesis of the 5'-carboxymethoxy derivative of enterolactone and 4'-O-carboxymethyl derivatives of daidzein and genistein, the respective compound was coupled to bovine serum albumin and then used as an antigen in the immunization of rabbits. The same derivatives of the phytoestrogen were used in preparing the europium tracers. After the enzymatic hydrolysis, the TR-FIA was carried out using the Victor 1420 multilabel counter. The method has sufficient sensitivity to measure the phytoestrogens at concentrations even below 5 nmol/l. The intra- and inter-assay coefficients of variation, at three different concentrations, varied from 1.9 to 5.3 and from 2.4 to 9.7, respectively. We measured urinary enterolactone, genistein and daidzein in 215 samples from Finnish healthy women and found that more than 50% of the values ranged between 1 and 7, <0.1 and 0.6 and below 0.6 micromol/24 h, respectively. The TR-FIA method including only a hydrolysis step gave higher values than those measured by gas chromatography-mass spectrometry (GC-MS). However, the assay results by the present method showed strong correlation with those obtained by GC-MS. It is concluded that the TR-FIA is suitable for population screening of urinary phytoestrogens. PMID:10822017

  2. Phytoestrogens and mycotoxins in Iowa streams: An examination of underinvestigated compounds in agricultural basins

    USGS Publications Warehouse

    Kolpin, Dana W.; Hoerger, Corinne C.; Meyer, Michael T.; Wettstein, Felix E.; Hubbard, Laura E.; Bucheli, Thomas D.

    2010-01-01

    This study provides the first broad-scale investigation on the spatial and temporal occurrence of phytoestrogens and mycotoxins in streams in the United States. Fifteen stream sites across Iowa were sampled five times throughout the 2008 growing season to capture a range of climatic and crop-growth conditions. Basin size upstream from sampling sites ranged from 7 km2 to >836,000 km2 Atrazine (herbicide) also was measured in all samples as a frame-of-reference agriculturally derived contaminant. Target compounds were frequently detected in stream samples: atrazine (100%), formononetin (80%), equol (45%), deoxynivalenol (43%), daidzein (32%), biochanin A (23%), zearalenone (13%), and genistein (11%). The nearly ubiquitous detection of formononetin (isoflavone) suggests a widespread agricultural source, as one would expect with the intense row crop and livestock production present across Iowa. Conversely, the less spatially widespread detections of deoxynivalenol (mycotoxin) suggest a more variable source due to the required combination of proper host and proper temperature and moisture conditions necessary to promote Fusarium spp. infections. Although atrazine concentrations commonly exceeded 100 ng L-1 (42/75 measurements), only deoxynivalenol (6/56 measurements) had concentrations that occasionally exceeded this level. Temporal patterns in concentrations varied substantially between atrazine, formononetin, and deoxynivalenol, as one would expect for contaminants with different source inputs and processes of formation and degradation. The greatest phytoestrogen and mycotoxin concentrations were observed during spring snowmelt conditions. Phytoestrogens and mycotoxins were detected at all sampling sites regardless of basin size. The ecotoxicological effects from long-term, low-level exposures to phytoestrogens and mycotoxins or complex chemicals mixtures including these compounds that commonly take place in surface water are poorly understood and have yet to be

  3. Phytoestrogens and mycotoxins in Iowa streams: An examination of underinvestigated compounds in agricultural basins

    USGS Publications Warehouse

    Kolpin, D.W.; Hoerger, C.C.; Meyer, M.T.; Wettstein, F.E.; Hubbard, L.E.; Bucheli, T.D.

    2010-01-01

    This study provides the first broad-scale investigation on the spatial and temporal occurrence of phytoestrogens and mycotoxins in streams in the United States. Fifteen stream sites across Iowa were sampled five times throughout the 2008 growing season to capture a range of climatic and crop-growth conditions. Basin size upstream from sampling sites ranged from 7 km2 to >836,000 km2. Atrazine (herbicide) also was measured in all samples as a frame-ofreference agriculturally derived contaminant. Target compounds were frequently detected in stream samples: atrazine (100%), formononetin (80%), equol (45%), deoxynivalenol (43%), daidzein (32%), biochanin A (23%), zearalenone (13%), and genistein (11%). Th e nearly ubiquitous detection of formononetin (isoflavone) suggests a widespread agricultural source, as one would expect with the intense row crop and livestock production present across Iowa. Conversely, the less spatially widespread detections of deoxynivalenol (mycotoxin) suggest a more variable source due to the required combination of proper host and proper temperature and moisture conditions necessary to promote Fusarium spp. infections. Although atrazine concentrations commonly exceeded 100 ng L-1 (42/75 measurements), only deoxynivalenol (6/56 measurements) had concentrations that occasionally exceeded this level. Temporal patterns in concentrations varied substantially between atrazine, formononetin, and deoxynivalenol, as one would expect for contaminants with different source inputs and processes of formation and degradation. The greatest phytoestrogen and mycotoxin concentrations were observed during spring snowmelt conditions. Phytoestrogens and mycotoxins were detected at all sampling sites regardless of basin size. The ecotoxicological effects from long-term, low-level exposures to phytoestrogens and mycotoxins or complex chemicals mixtures including these compounds that commonly take place in surface water are poorly understood and have yet to be

  4. Coexposure to phytoestrogens and bisphenol a mimics estrogenic effects in an additive manner.

    PubMed

    Katchy, Anne; Pinto, Caroline; Jonsson, Philip; Nguyen-Vu, Trang; Pandelova, Marchela; Riu, Anne; Schramm, Karl-Werner; Samarov, Daniel; Gustafsson, Jan-Åke; Bondesson, Maria; Williams, Cecilia

    2014-03-01

    Endocrine-disrupting chemicals (EDC) are abundant in our environment. A number of EDCs, including bisphenol A (BPA) can bind to the estrogen receptors (ER), ERα and ERβ, and may contribute to estrogen-linked diseases such as breast cancer. Early exposure is of particular concern; many EDCs cross the placenta and infants have measurable levels of, eg, BPA. In addition, infants are frequently fed soy-based formula (SF) that contains phytoestrogens. Effects of combined exposure to xeno- and phytoestrogens are poorly studied. Here, we extensively compared to what extent BPA, genistein, and an extract of infant SF mimic estrogen-induced gene transcription and cell proliferation. We investigated ligand-specific effects on ER activation in HeLa-ERα and ERβ reporter cells; on proliferation, genome-wide gene regulation and non-ER-mediated effects in MCF7 breast cancer cells; and how coexposure influenced these effects. The biological relevance was explored using enrichment analyses of differentially regulated genes and clustering with clinical breast cancer profiles. We demonstrate that coexposure to BPA and genistein, or SF, results in increased functional and transcriptional estrogenic effects. Using statistical modeling, we determine that BPA and phytoestrogens act in an additive manner. The proliferative and transcriptional effects of the tested compounds mimic those of 17β-estradiol, and are abolished by cotreatment with an ER antagonist. Gene expression profiles induced by each compound clustered with poor prognosis breast cancer, indicating that exposure may adversely affect breast cancer prognosis. This study accentuates that coexposure to BPA and soy-based phytoestrogens results in additive estrogenic effects, and may contribute to estrogen-linked diseases, including breast cancer.

  5. Comprehensive assessment of hormones, phytoestrogens, and estrogenic activity in an anaerobic swine waste lagoon.

    PubMed

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Meissner, Benjamin M; Worley-Davis, Lynn; Williams, C Michael; Lee, Boknam; Kullman, Seth W

    2013-12-01

    In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge were assessed using LC/MS-MS, and yeast estrogen screen was used to determine estrogenic activity. Of the hormone analytes, steroidal estrogens were more abundant than androgens or progesterone, with estrone being the predominant estrogen species. Conjugated hormones were detected only at low levels. The isoflavone metabolite equol was by far the predominant phytoestrogen species, with daidzein, genistein, formononetin, and coumestrol present at lower levels. Phytoestrogens were often more abundant than steroidal estrogens, but contributed minimally toward total estrogenic activity. Analytes were significantly elevated in the solid phases of the lagoon; although low observed log KOC values suggest enhanced solubility in the aqueous phase, perhaps due to dissolved or colloidal organic carbon. The association with the solid phase, as well as recalcitrance of analytes to anaerobic degradation, results in a markedly elevated load of analytes and estrogenic activity within lagoon sludge. Overall, findings emphasize the importance of adsorption and transformation processes in governing the fate of these compounds in lagoon waste, which is ultimately used for broadcast application as a fertilizer. PMID:24144340

  6. Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.

    PubMed

    Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2010-12-01

    Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes.

  7. Transport of steroid hormones, phytoestrogens, and estrogenic activity across a swine lagoon/sprayfield system.

    PubMed

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Williams, C Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W

    2014-10-01

    The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.

  8. Comprehensive assessment of hormones, phytoestrogens, and estrogenic activity in an anaerobic swine waste lagoon

    USGS Publications Warehouse

    Yost, Erin E.; Meyer, Michael T.; Dietze, Julie E.; Meissner, Benjamin M.; Williams, Mike; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W.

    2013-01-01

    In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge were assessed using LC/MS-MS, and yeast estrogen screen was used to determine estrogenic activity. Of the hormone analytes, steroidal estrogens were more abundant than androgens or progesterone, with estrone being the predominant estrogen species. Conjugated hormones were detected only at low levels. The isoflavone metabolite equol was by far the predominant phytoestrogen species, with daidzein, genistein, formononetin, and coumestrol present at lower levels. Phytoestrogens were often more abundant than steroidal estrogens, but contributed minimally towards total estrogenic activity. Analytes were significantly elevated in the solid phases of the lagoon; although low observed log KOC values suggest enhanced solubility in the aqueous phase, perhaps due to dissolved or colloidal organic carbon. The association with the solid phase, as well as recalcitrance of analytes to anaerobic degradation, results in a markedly elevated load of analytes and estrogenic activity within lagoon sludge. Overall, findings emphasize the importance of adsorption and transformation processes in governing the fate of these compounds in lagoon waste, which is ultimately used for broadcast application as a fertilizer.

  9. Biodegradation of the phytoestrogen luteolin by the endophytic fungus Phomopsis liquidambari.

    PubMed

    Wang, Hong-Wei; Zhang, Wei; Su, Chun-Lun; Zhu, Hong; Dai, Chuan-Chao

    2015-06-01

    Phytoestrogens are plant-derived hormonally-active compounds known to cause varied reproductive, immunosuppressive and behavioral effects in vertebrates. In this study, biodegradation of luteolin, a common phytoestrogen, was investigated during incubation with endophytic fungus Phomopsis liquidambari. The optimum concentration of luteolin as sole carbon source supplied in culture was 200 mg L(-1), which allowed 97 and 99 % degradation of luteolin by P. liquidambari in liquid culture and soil conditions, respectively. The investigation of the fungal metabolic pathway showed that luteolin was first decomposed to caffeic acid and phloroglucinol. These intermediate products were degraded to protocatechuic acid and hydroxyquinol, respectively, and then rings were opened by ring-cleavage dioxygenases. Two novel genes encoding the protocatechuate 3,4-dioxygenase and hydroxyquinol 1,2-dioxygenase were successfully cloned. Reverse-transcription quantitative polymerase chain reaction demonstrated that expression levels of mRNA of these two genes increased significantly after P. liquidambari was induced by the intermediate products caffeic acid and phloroglucinol, respectively. These results revealed that P. liquidambari can biodegrade luteolin efficiently and could potentially be used to bioremediate phytoestrogen contamination.

  10. Comprehensive assessment of hormones, phytoestrogens, and estrogenic activity in an anaerobic swine waste lagoon.

    PubMed

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Meissner, Benjamin M; Worley-Davis, Lynn; Williams, C Michael; Lee, Boknam; Kullman, Seth W

    2013-12-01

    In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge were assessed using LC/MS-MS, and yeast estrogen screen was used to determine estrogenic activity. Of the hormone analytes, steroidal estrogens were more abundant than androgens or progesterone, with estrone being the predominant estrogen species. Conjugated hormones were detected only at low levels. The isoflavone metabolite equol was by far the predominant phytoestrogen species, with daidzein, genistein, formononetin, and coumestrol present at lower levels. Phytoestrogens were often more abundant than steroidal estrogens, but contributed minimally toward total estrogenic activity. Analytes were significantly elevated in the solid phases of the lagoon; although low observed log KOC values suggest enhanced solubility in the aqueous phase, perhaps due to dissolved or colloidal organic carbon. The association with the solid phase, as well as recalcitrance of analytes to anaerobic degradation, results in a markedly elevated load of analytes and estrogenic activity within lagoon sludge. Overall, findings emphasize the importance of adsorption and transformation processes in governing the fate of these compounds in lagoon waste, which is ultimately used for broadcast application as a fertilizer.

  11. Modulation of monoamine neurotransmitters in fighting fish Betta splendens exposed to waterborne phytoestrogens.

    PubMed

    Clotfelter, Ethan D; McNitt, Meredith M; Carpenter, Russ E; Summers, Cliff H

    2010-12-01

    Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes. PMID:20012186

  12. Biodegradation of the phytoestrogen luteolin by the endophytic fungus Phomopsis liquidambari.

    PubMed

    Wang, Hong-Wei; Zhang, Wei; Su, Chun-Lun; Zhu, Hong; Dai, Chuan-Chao

    2015-06-01

    Phytoestrogens are plant-derived hormonally-active compounds known to cause varied reproductive, immunosuppressive and behavioral effects in vertebrates. In this study, biodegradation of luteolin, a common phytoestrogen, was investigated during incubation with endophytic fungus Phomopsis liquidambari. The optimum concentration of luteolin as sole carbon source supplied in culture was 200 mg L(-1), which allowed 97 and 99 % degradation of luteolin by P. liquidambari in liquid culture and soil conditions, respectively. The investigation of the fungal metabolic pathway showed that luteolin was first decomposed to caffeic acid and phloroglucinol. These intermediate products were degraded to protocatechuic acid and hydroxyquinol, respectively, and then rings were opened by ring-cleavage dioxygenases. Two novel genes encoding the protocatechuate 3,4-dioxygenase and hydroxyquinol 1,2-dioxygenase were successfully cloned. Reverse-transcription quantitative polymerase chain reaction demonstrated that expression levels of mRNA of these two genes increased significantly after P. liquidambari was induced by the intermediate products caffeic acid and phloroglucinol, respectively. These results revealed that P. liquidambari can biodegrade luteolin efficiently and could potentially be used to bioremediate phytoestrogen contamination. PMID:25794548

  13. Reproductive toxicity of 2,4-toluenediamine in the rat. 2. Spermatogenic and hormonal effects

    SciTech Connect

    Thysen, B.; Bloch, E.; Varma, S.K.

    1985-01-01

    The present study was undertaken to evaluate the endocrinologic and spermatogenic effects of 2,4-toluenediamine (TDA) in the rat. Adult male rats were fed 0, 0.01, and 0.03% TDA ad libitum for 10 wk. At the end of wk 10 and at 11 wk post TDA treatment, the animals were killed, and cauda epididymal sperm counts and reproductive organ weights were determined. Blood samples were obtained for analyses of testosterone and gonadotropins. Treatment with 0.03% TDA for 10 wk reduced the weight of the seminal vesicles and epididymides and reduced serum testosterone levels. Cauda epididymal sperm counts were decreased in animals treated with 0.03% TDA for 10 wk and in TDA-treated animals placed on normal diet for 11 wk. Serum luteinizing hormone (LH) concentrations were increased and weights of epididymides and testes were reduced in 0.03%-TDA-treated animals placed on normal diet for 11 wk. The results indicate that TDA exerts a toxic effect on spermatogenesis and appears to affect androgen action production in the male rat. Since the males exhibited reduced cauda epididymal sperm counts 11 wk after 0.03% TDA treatment, it appears that TDA induced damage to the germinal components of the testes.

  14. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception.

    PubMed

    Oduwole, Olayiwola O; Vydra, Natalia; Wood, Nicholas E M; Samanta, Luna; Owen, Laura; Keevil, Brian; Donaldson, Mandy; Naresh, Kikkeri; Huhtaniemi, Ilpo T

    2014-06-01

    Testosterone (T), alone or in combination with progestin, provides a promising approach to hormonal male contraception. Its principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the testicular T production needed for spermatogenesis, while simultaneously maintaining the extragonadal androgen actions, such as potency and libido, to avoid hypogonadism. A serious drawback of the treatment is that a significant proportion of men do not reach azoospermia or severe oligozoospermia, commensurate with contraceptive efficacy. We tested here, using hypogonadal luteinizing hormone/choriongonadotropin receptor (LHCGR) knockout (LHR(-/-)) mice, the basic principle of the T-based male contraceptive method, that a specific T dose could maintain extragonadal androgen actions without simultaneously activating spermatogenesis. LHR(-/-) mice were treated with increasing T doses, and the responses of their spermatogenesis and extragonadal androgen actions (including gonadotropin suppression and sexual behavior) were assessed. Conspicuously, all dose responses to T were practically superimposable, and no dose of T could be defined that would maintain sexual function and suppress gonadotropins without simultaneously activating spermatogenesis. This finding, never addressed in clinical contraceptive trials, is not unexpected in light of the same androgen receptor mediating androgen actions in all organs. When extrapolated to humans, our findings may jeopardize the current approach to hormonal male contraception and call for more effective means of inhibiting intratesticular T production or action, to achieve consistent spermatogenic suppression.

  15. Haplotype analysis of ESR2 in Japanese patients with spermatogenic failure.

    PubMed

    Ogata, Tsutomu; Fukami, Maki; Yoshida, Rie; Nagata, Eiko; Fujisawa, Yasuko; Yoshida, Atsumi; Yoshimura, Yasunori

    2012-07-01

    The prevalence of spermatogenic failure (SF) has gradually increased during the past few decades at least in several countries. Although multiple factors would be involved in this phenomenon, one important factor would be excessive estrogen effects via estrogen receptors (ERs). Thus, we performed haplotype analysis of ESR2 encoding ERβ in 125 Japanese SF patients and 119 age-matched control males, using single nucleotide polymorphisms (SNPs) 1-9 that are widely distributed on the ~120-kb genomic sequence of ESR2. Consequently, a linkage disequilibrium (LD) block was detected in an ~60-kb region encompassing SNPs 2-7 in both groups, and four major estimated haplotypes were identified within the LD block. Furthermore, the most prevalent 'TGTAGA' haplotype was found to be significantly associated with SF, with the P-value obtained by the Cochran-Armitage trend test (0.0029) being lower than that obtained by a 100 000-times permutation test (0.0038) to cope with the problem of multiple comparisons. The results, in conjunction with our previous data indicating lack of a susceptibility factor on ESR1 encoding ERα, imply that the specific 'TGTAGA' haplotype of ESR2 raises the susceptibility to the development of SF.

  16. Gas chromatographic-mass spectrometric fragmentation study of phytoestrogens as their trimethylsilyl derivatives: Identification in soy milk and wastewater samples

    USGS Publications Warehouse

    Ferrer, I.; Barber, L.B.; Thurman, E.M.

    2009-01-01

    An analytical method for the identification of eight plant phytoestrogens (biochanin A, coumestrol, daidzein, equol, formononetin, glycitein, genistein and prunetin) in soy products and wastewater samples was developed using gas chromatography coupled with ion trap mass spectrometry (GC/MS-MS). The phytoestrogens were derivatized as their trimethylsilyl ethers with trimethylchlorosilane (TMCS) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA). The phytoestrogens were isolated from all samples with liquid-liquid extraction using ethyl acetate. Daidzein-d4 and genistein-d4 labeled standards were used as internal standards before extraction and derivatization. The fragmentation patterns of the phytoestrogens were investigated by isolating and fragmenting the precursor ions in the ion-trap and a typical fragmentation involved the loss of a methyl and a carbonyl group. Two characteristic fragment ions for each analyte were chosen for identification and confirmation. The developed methodology was applied to the identification and confirmation of phytoestrogens in soy milk, in wastewater effluent from a soy-milk processing plant, and in wastewater (influent and effluent) from a treatment plant. Detected concentrations of genistein ranged from 50,000 ??g/L and 2000 ??g/L in soy milk and in wastewater from a soy-plant, respectively, to 20 ??g/L and <1 ??g/L for influent and effluent from a wastewater treatment plant, respectively. ?? 2009 Elsevier B.V.

  17. Phytoestrogens selective for the estrogen receptor beta exert anti-androgenic effects in castration resistant prostate cancer.

    PubMed

    Thelen, Paul; Wuttke, Wolfgang; Seidlová-Wuttke, Dana

    2014-01-01

    Prostate cancer is the leading cause of cancer death in men of the Western world. A castration-resistant prostate cancer (CRPC) eventually will arise when a local restricted prostate carcinoma was not cured duly by radical prostatectomy or radiation therapy. Although androgen ablation therapies are considered the gold standard for treatments of advanced prostate cancer there is no curative therapy available at present. In previous pre-clinical and clinical trials several phytoestrogens were investigated for their anticancer potential in various models for prostate cancer. Phytoestrogens feature tumour preventive characteristics and most probably are involved in the low incidence rate of hormone related cancers in Asian countries. Phytoestrogens such as isoflavones can have a marked impact on the most essential therapy target of CRPC i.e. the androgen receptor. Furthermore, functional analyses solidified the notion of such drugs as androgen antagonistic. Phytoestrogens commonly feature low toxicity combined with a potential of targeted therapy. Thus, these drugs qualify for conceivable implementation in prostate cancer patients under active surveillance. In addition, relapse prevention with these drugs after radical prostatectomy or radiation therapy might be considered. This article is part of a Special Issue entitled 'Phytoestrogens'.

  18. Simultaneous determination of phytoestrogens and key metabolites in breast cancer patients' urine by liquid chromatography-tandem mass spectrometry.

    PubMed

    Yu, Jing; Wu, Qian; Qiao, Shanlei; Yu, Zeping; Jin, Nianzu; Yu, Boyang

    2009-12-01

    A novel, selective and sensitive liquid chromatography-tandem mass spectrometry method has been developed and validated for the simultaneous determination of phytoestrogens and their key metabolites in human urine in this study. This method includes internal standard (IS) screening, analytical sample preparation procedure establishment, and linear range investigation. The analytical sample was extracted by liquid-liquid extraction from urine sample. The phytoestrogens and related key metabolites were separated with Agilent Zorbax Eclipse XDB-C18 chromatographic column using methanol and water as mobile phase. The Quattro premier MICROMASS mass spectrometer in negative ion selected reaction monitoring (SRM) mode using electrospray ionization was applied to detect the phytoestrogens and key metabolites. To validate the developed liquid chromatography-tandem mass spectrometry method, the intra- and inter-day precisions, specificity, sensitivity, reproducibility, and sample detective concentration range were evaluated. This is the first reported phytoestrogens analysis and validation study that demonstrates the feasibility of using liquid chromatography-electrospray ionization mass spectrometry to simultaneously analyze ten analytes including both phytoestrogens and their key metabolites in urine samples collected for epidemiological studies in human.

  19. Exercise and supraphysiological dose of nandrolone decanoate increase apoptosis in spermatogenic cells.

    PubMed

    Shokri, Saeed; Aitken, Robert John; Abdolvahhabi, Mirabbas; Abolhasani, Farid; Ghasemi, Fahimeh Mohammad; Kashani, Iraj; Ejtemaeimehr, Shahram; Ahmadian, Shahin; Minaei, Bagher; Naraghi, Mohammad Ali; Barbarestani, Mohammad

    2010-04-01

    Anabolic-androgenic steroids are used at high doses by athletes for improving athletic ability, physical appearance and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of anabolic-androgenic steroids may influence the hypothalamic-pituitary-gonadal axis, which can in turn affect testicular apoptosis. However, the effect of the combination of exercise and high dose of anabolic-androgenic steroids on testicular apoptosis is not known. We investigated the combined effects of exercise and high doses of nandrolone decanoate on apoptosis in the spermatogenic cell lineage. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (Sham); nandrolone decanoate (10 mg/kg/weekly) (nandrolone decanoate); exercise (1 hr/day, 5 days a week) (exercise); nandrolone decanoate (10 mg/kg/weekly) and exercise (1 hr/day, 5 days a week) (nandrolone decanoate exercise); and sedentary control without any injection or exercise (Control). Apoptosis in the male germ line was characterized by TUNEL, caspase-3 assay and transmission electron microscopy. The weights of the testis and accessory sex organs, as well as sperm parameters significantly decreased in the experimental groups relative to the sham and control groups (p < or = 0.05). Germ cell apoptosis and a significant decrease in the number of germ cell layers in nandrolone decanoate exercise-treated testes were observed (p < or = 0.05). Exercise training seems to increase the extent of apoptotic changes caused by supraphysiological dose of nandrolone decanoate in rats, which in turn affects fertility.

  20. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure.

    PubMed

    Lardone, M C; Castillo, P; Valdevenito, R; Ebensperger, M; Ronco, A M; Pommer, R; Piottante, A; Castro, A

    2010-08-01

    There is evidence that impaired spermatogenesis is associated with an imbalance in the oestradiol/testosterone ratio and with Leydig cell (LC) dysfunction. In testis, P450-aromatase, encoded by CYP19, is responsible for the conversion of testosterone to oestradiol. The aims of this study were to quantify CYP19 mRNA expression, aromatase activity and protein localization, and to measure the oestradiol to testosterone ratio in testicular tissues of men with spermatogenic impairment. Twenty-four men with complete Sertoli cell-only syndrome (SCOS), 14 with focal SCOS, 14 with maturation arrest (MA), 8 with mixed atrophy and 30 controls with normal spermatogenesis were subjected to testicular biopsy. All subjects underwent a physical examination, cytogenetic and serum hormonal studies. Testicular CYP19 mRNA was quantified using real time RT-PCR. Testicular aromatase activity was measured using the (3)H(2)0 assay and protein expression was evaluated using immunohistochemistry. In cases, serum testosterone and oestradiol were normal, but the testosterone/LH ratio was lower compared with controls (p < 0.05). Aromatase was localized in the Leydig, Sertoli and germ cells of all tissues, although stronger intensity was observed in LC. Aromatase mRNA and activity were not altered in cases and correlated positively with LC number (r = 0.516 and r = 0.369; p < 0.008). The intratesticular oestradiol/testosterone ratio was elevated (p = 0.005) in complete SCOS patients compared with controls. In conclusion, testicular aromatase seems to be normal in most subjects with impaired spermatogenesis. However, an altered intratesticular oestradiol/testosterone ratio in some patients with complete SCOS suggests that aromatase is increased, which might contribute to Leydig cell dysfunction.

  1. Elucidating the identity and behavior of spermatogenic stem cells in the mouse testis.

    PubMed

    Yoshida, Shosei

    2012-09-01

    Spermatogenesis in mice and other mammalians is supported by a robust stem cell system. Stem cells maintain themselves and continue to produce progeny that will differentiate into sperm over a long period. The pioneering studies conducted from the 1950s to the 1970s, which were based largely on extensive morphological analyses, have established the fundamentals of mammalian spermatogenesis and its stem cells. The prevailing so-called A(single) (A(s)) model, which was originally established in 1971, proposes that singly isolated A(s) spermatogonia are in fact the stem cells. In 1994, the first functional stem cell assay was established based on the formation of repopulating colonies after transplantation in germ cell-depleted host testes, which substantially accelerated the understanding of spermatogenic stem cells. However, because testicular tissues are dissociated into single-cell suspension before transplantation, it was impossible to evaluate the A(s) and other classical models solely by this technique. From 2007 onwards, functional assessment of stem cells without destroying the tissue architecture has become feasible by means of pulse-labeling and live-imaging strategies. Results obtained from these experiments have been challenging the classical thought of stem cells, in which stem cells are a limited number of specialized cells undergoing asymmetric division to produce one self-renewing and one differentiating daughter cells. In contrast, the emerging data suggest that an extended and heterogeneous population of cells exhibiting different degrees of self-renewing and differentiating probabilities forms a reversible, flexible, and stochastic stem cell system as a population. These features may lead to establishment of a more universal principle on stem cells that is shared by other systems.

  2. Dietary phytoestrogens present in soy dramatically increase cardiotoxicity in male mice receiving a chemotherapeutic tyrosine kinase inhibitor.

    PubMed

    Harvey, Pamela Ann; Leinwand, Leslie Anne

    2015-01-01

    Use of soy supplements to inhibit cancer cell growth is increasing among patients due to the perception that phytoestrogens in soy inhibit carcinogenesis via induction of apoptosis. Genistein, the most prevalent phytoestrogen in soy, is a potent endocrine disruptor and tyrosine kinase inhibitor (TKI) that causes apoptosis in many cells types. Chemotherapeutic TKIs limit cancer cell growth via the same mechanisms. However, TKIs such as Sunitinib cause cardiotoxicity in a significant number of patients. Molecular interactions between Sunitinib and dietary TKIs like genistein have not been examined in cardiomyocytes. Significant lethality occurred in mice treated with Sunitinib and fed a phytoestrogen-supplemented diet. Isolated cardiomyocytes co-treated with genistein and Sunitinib exhibited additive inhibition of signaling molecules important for normal cardiac function and increased apoptosis compared with Sunitinib alone. Thus, dietary soy supplementation should be avoided during administration of Sunitinib due to exacerbated cardiotoxicity, despite evidence for positive effects in cancer.

  3. Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

    PubMed

    Lopes, Alexandra M; Aston, Kenneth I; Thompson, Emma; Carvalho, Filipa; Gonçalves, João; Huang, Ni; Matthiesen, Rune; Noordam, Michiel J; Quintela, Inés; Ramu, Avinash; Seabra, Catarina; Wilfert, Amy B; Dai, Juncheng; Downie, Jonathan M; Fernandes, Susana; Guo, Xuejiang; Sha, Jiahao; Amorim, António; Barros, Alberto; Carracedo, Angel; Hu, Zhibin; Hurles, Matthew E; Moskovtsev, Sergey; Ober, Carole; Paduch, Darius A; Schiffman, Joshua D; Schlegel, Peter N; Sousa, Mário; Carrell, Douglas T; Conrad, Donald F

    2013-03-01

    Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 × 10(-3)), rare X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 × 10(-3)), and rare Y-linked duplications by 88% (OR 1.88 [1.13-3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5)). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes. PMID:23555275

  4. Phytoestrogens enhance antioxidant enzymes after swimming exercise and modulate sex hormone plasma levels in female swimmers.

    PubMed

    Mestre-Alfaro, Antonia; Ferrer, Miguel D; Sureda, Antoni; Tauler, Pedro; Martínez, Elisa; Bibiloni, Maria M; Micol, Vicente; Tur, Josep A; Pons, Antoni

    2011-09-01

    Our aim was to investigate the effects of diet supplementation with phytoestrogens on sex hormone levels, antioxidant adaptive responses and oxidative damage induced by exercise. Ten female swimmers participated for 26 days in a diet intervention with either a functional beverage rich in vitamins C and E or the same beverage but also supplemented with Lippia citriodora extract (PLX) containing 20 mg/100 ml verbascoside. After the intervention all subjects participated in a swimming session for 30 min maintaining the intensity at about 75-80% of their individual best performance time for a 50-m swim. In lymphocytes, the superoxide dismutase activity increased after exercise, with a higher increase in the PLX group. Swimming increased the erythrocyte activity of glutathione peroxidase and glutathione reductase in the PLX group. Purified glutathione reductase activity increased after an in vitro incubation with PLX. No effects were observed on the lymphocyte levels of malondialdehyde and carbonyls, but exercise increased the percentage of high-damaged lymphocytes 2.8 times in the placebo group and 1.5 times in the PLX group. PLX decreased the levels of 17-β-estradiol and testosterone and increased the levels of the sex hormone binding globulin. In conclusion, supplementation with phytoestrogens enhances the glutathione-dependent enzyme activities in erythrocytes and the superoxide dismutase activity in lymphocytes in response to exercise. PLX also shows direct antioxidant properties, by increasing glutathione reductase enzyme activity in vitro. Supplementation with phytoestrogens also decreases the plasma steroid hormone levels, pointing towards a possible agonistic effect of verbascoside in the hypothalamic regulation of estradiol synthesis.

  5. Characterization of estrogenicity of phytoestrogens in an endometrial-derived experimental model.

    PubMed Central

    Hopert, A C; Beyer, A; Frank, K; Strunck, E; Wünsche, W; Vollmer, G

    1998-01-01

    Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17beta-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9721258

  6. Effect of dietary phytoestrogens on human growth regulation: imprinting in health & disease.

    PubMed

    Griffiths, K; Wilson, D W; Singh, R B; De Meester, F

    2014-11-01

    This group has advocated a return to the notional Palæolithic diet with fruits, vegetables, roots, leaves, seeds, phytochemical antioxidants and proteins, etc. Phytoestrogens, viz. lignans, isoflavonoids and flavonoids are weak oestrogenic constituents of such a diet and may have a considerable impact on human health and disease. The aim of this paper was to conduct a preliminary overview of about 2000 research-led studies from the 1930s to the present time reported in the literature on flavonoids/isoflavonoids/lignans and to assemble evidence for a future strictly formal literature review on the health benefits and risks of flavonoids in a variety of diseases. PMID:25673549

  7. Effect of dietary phytoestrogens on human growth regulation: imprinting in health & disease

    PubMed Central

    Griffiths, K.; Wilson, D.W.; Singh, R.B.; De Meester, F.

    2014-01-01

    This group has advocated a return to the notional Palæolithic diet with fruits, vegetables, roots, leaves, seeds, phytochemical antioxidants and proteins, etc. Phytoestrogens, viz. lignans, isoflavonoids and flavonoids are weak oestrogenic constituents of such a diet and may have a considerable impact on human health and disease. The aim of this paper was to conduct a preliminary overview of about 2000 research-led studies from the 1930s to the present time reported in the literature on flavonoids/isoflavonoids/lignans and to assemble evidence for a future strictly formal literature review on the health benefits and risks of flavonoids in a variety of diseases. PMID:25673549

  8. Effect of dietary phytoestrogens on human growth regulation: imprinting in health & disease.

    PubMed

    Griffiths, K; Wilson, D W; Singh, R B; De Meester, F

    2014-11-01

    This group has advocated a return to the notional Palæolithic diet with fruits, vegetables, roots, leaves, seeds, phytochemical antioxidants and proteins, etc. Phytoestrogens, viz. lignans, isoflavonoids and flavonoids are weak oestrogenic constituents of such a diet and may have a considerable impact on human health and disease. The aim of this paper was to conduct a preliminary overview of about 2000 research-led studies from the 1930s to the present time reported in the literature on flavonoids/isoflavonoids/lignans and to assemble evidence for a future strictly formal literature review on the health benefits and risks of flavonoids in a variety of diseases.

  9. Dietary phytoestrogens and cancer: in vitro and in vivo studies.

    PubMed

    Adlercreutz, H; Mousavi, Y; Clark, J; Höckerstedt, K; Hämäläinen, E; Wähälä, K; Mäkelä, T; Hase, T

    1992-03-01

    Thirty postmenopausal women (11 omnivores, 10 vegetarians and 9 apparently healthy women with surgically removed breast cancer) were investigated with regard to the association of their urinary excretion of estrogens, lignans and isoflavonoids (all diphenols) with plasma sex hormone binding globulin (SHBG). A statistically significant positive correlation between urinary total diphenol excretion and plasma SHBG was found which remained statistically significant after elimination of the confounding effect of body mass determined by body mass index (BMI). Furthermore we found a statistically significant negative correlation between plasma SHBG and urinary excretion of 16 alpha-hydroxyestrone and estriol which also remained significant after eliminating the effect of BMI. Furthermore we observed that enterolactone (Enl) stimulates the synthesis of SHBG by HepG2 liver cancer cells in culture acting synergistically with estradiol and at physiological concentrations. Enl was rapidly conjugated by the liver cells, mainly to its monosulfate. Several lignans and the isoflavonoids daidzein and equol were found to compete with estradiol for binding to the rat uterine type II estrogen binding site (the s.c. bioflavonoid receptor). It is suggested that lignans and isoflavonoids may affect uptake and metabolism of sex hormones by participating in the regulation of plasma SHBG levels and in this way influence their biological activity and that they may inhibit cancer cell growth like some flavonoids by competing with estradiol for the type II estrogen binding sites.

  10. Sertoli cell numbers and spermatogenic efficiency are increased in inducible nitric oxide synthase mutant mice.

    PubMed

    Auharek, S A; Avelar, G F; Lara, N L M; Sharpe, R M; França, L R

    2011-12-01

    Nitric oxide (NO) is produced via oxidation of l-arginine by nitric oxide synthases (NOSs), and is known as inducible (iNOS), neuronal, endothelial or testis-specific. Suggesting important functions for NOS in the normal rat and mouse testis, iNOS is reported to be constitutively expressed in Leydig cells (LC), Sertoli cells (SC) and germ cells. In our study, we sought to provide further insights into the roles of iNOS in the adult mouse testis using iNOS(-/-) mice. Perfusion-fixed testes from wild type (WT) and iNOS(-/-) mice were used for histological and stereological evaluations. Some of the mice had been injected with (3) H-thymidine to label proliferating cells and to determine the duration of spermatogenesis that was unaffected in iNOS(-/-) mice. Both LC nuclear volume and individual cell size were significantly decreased in iNOS(-/-) mice, but the total number of LC per testis was increased (p < 0.05) by approximately 16%. The number of SC per testis was strikingly increased (approximately twofold) in iNOS(-/-) mice, and testis weight and DSP per gram of testis (spermatogenic efficiency) were similarly increased. The anogenital distance was also significantly increased in iNOS(-/-) mice, and this key endpoint suggests that the augmentation observed for the SC number may be related to increased foetal T-exposure during the masculinization programming window. Compared with WT testes, the numbers of spermatocytes and spermatids and SC per tubule cross sections were significantly increased in iNOS(-/-) mice. Except for stages V-VI and VII-VIII, iNOS(-/-) mice exhibited approximately 3.5-fold fewer apoptotic germ cells than in WT mice. Taken together, our results provide new evidence that iNOS plays an important role in numerical and functional regulation of key somatic cells in the testis, which in turn impacts on germ cells and their survival and thus on daily sperm production.

  11. Effect of maca supplementation on bovine sperm quantity and quality followed over two spermatogenic cycles.

    PubMed

    Clément, C; Kneubühler, J; Urwyler, A; Witschi, U; Kreuzer, M

    2010-07-15

    Maca (Lepidium meyenii Walpers), is an Andean crop that grows between 3,800 and 4,500 m a.s.l. The persistent interest in this plant is based on its assumed effects on fertility of male mammals due to the prevalence of certain, partially specific, secondary compounds. The present study aimed at evaluating the effect of maca supplementation on quality and quantity of semen, mating behavior, and clinical status of peripubertal breeding bulls. The experiment followed a cross-over design lasting for 23 wk with 3 wk of adaptation and baseline measurements, and 2 x 10 wk of treatment feeding thus covering two times the complete 8-wk spermatogenic cycle. Seventy-eight 55 wk to 84 wk old breeding bulls received either no maca (control) or maca (233 mg dried hypocotyls/kg body weight/day) for 10 wk followed by 10 wk without maca (maca early) or maca only in the last 10 wk (maca late). Measurements were always made in the last 2 wk of each period. Apart from standard analyses, ejaculates were analyzed by flow cytometry. Data was evaluated by analysis of variance considering the repeated measurement structure of the data. Significant treatment by measurement period indicated direct or carry-over effects of maca. Maca supplementation had no direct effect on body weight, testes circumference, rectal temperature, mating behavior, and ejaculate volume. However, supplementing maca in the first 10 wk period increased the number of sperms in the second 10 wk period, i.e., when the animals no longer received maca. The DNA fragmentation index and the visually assessed motility of the sperms of bulls, that initially showed a borderline sperm quality, were significantly improved with early maca supplementation, while no such effect was observed in the two other groups. No effects occurred in the proportion of intact sperm plasma membranes or acrosomes or both. In conclusion, maca supplementation seems to improve sperm quantity and quality of bulls to a certain degree, while mating

  12. Molecular cloning of a novel nuclear factor, TDRP1, in spermatogenic cells of testis and its relationship with spermatogenesis

    SciTech Connect

    Wang, Xuanchun; Jiang, Haowen; Zhou, Wenbai; Zhang, Zhaoyun; Yang, Zhihong; Lu, Yong; Lu, Bin; Wang, Xiang; Ding, Qiang; Hu, Renming

    2010-03-26

    We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3 weeks postpartum, and peaked at 2 months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.

  13. Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption

    PubMed Central

    Bayele, Henry K.; Balesaria, Sara; Srai, Surjit K.S.

    2015-01-01

    Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis. PMID:26546695

  14. Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens

    SciTech Connect

    Lyn-Cook, B.D.; Blann, E.; Bo, J.

    1995-01-01

    Specific gene hypermethylation has been shown in DNA from neonatal rats exposed to the phytoestrogens, coumestrol, and equol. The pancreas is an organ in which estrogen receptors have been shown to be present. Studies have correlated the development of acute pancreatitis with rising levels of human estrogen binding proteins. Neonatal rats were dosed with 10 or 100 {mu}g of coumestrol or equol on postnatal day (PND) 1-10. The animals were sacrificed at Day 15. The pancreas was excised and pancreatic acinar cells isolated for molecular analysis. DNA was isolated from the cells by lysis in TEN-9 buffer supplemented with proteinase K and 0.1% SDS. High molecular weight (HMW) DNA was digested with the methylated DNA specific restriction enzymes, Hpa II and Msp I, for determination of methylation profiles. Both coumestrol and equol at high doses caused hypermethylation of the c-H-ras proto-oncogene. No hypermethylation or hypomethylation was observed in the proto-oncogenes, c-myc or c-fos. Methylation is thought to be an epigenetic mechanism involved in the activation (hypomethylation) or inactivation (hypermethylation) of cellular genes which are known to play a role in carcinogenesis. Epidemiology studies have shown that equol may have anti-carcinogenic effects on some hormone-dependent cancers. Additional studies are needed to further understand the role of phytoestrogens and methylation in relation to pancreatic disorders. 15 refs., 4 figs.

  15. Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption.

    PubMed

    Bayele, Henry K; Balesaria, Sara; Srai, Surjit K S

    2015-12-01

    Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis.

  16. Gastrointestinal metabolism of phytoestrogens in lactating dairy cows fed silages with different botanical composition.

    PubMed

    Njåstad, K M; Adler, S A; Hansen-Møller, J; Thuen, E; Gustavsson, A-M; Steinshamn, H

    2014-12-01

    Dietary phytoestrogens are metabolized or converted in the gastrointestinal tract of ruminants, only limited knowledge exists on the extent and location of this conversion in vivo. The objective of this study was to quantify the gastro-intestinal metabolism of phytoestrogens in lactating dairy cows fed silages with different botanical composition. Four lactating rumen cannulated Norwegian Red cattle were assigned to a 4 × 4 Latin square with 1 cow per treatment period of 3 wk. The 4 treatment silages were prepared from grasslands with different botanical compositions: organically managed short-term timothy (Phleum pratense L.) and red clover (Trifolium pratense L.) ley (2 yr old: ORG-SG); organically managed long-term grassland with a high proportion of unsown species (6 yr old; ORG-LG); conventionally managed perennial ryegrass (Lolium perenne L.) ley (CON-PR); and conventionally managed timothy ley (CON-TI). The herbages were cut, wilted, and preserved with additive in round bales, fed as a mix of the first and third cut at 90% of ad libitum intake, and contributed to 70% of the total dry matter intake. Milk, feed, omasal digesta, urine, and feces were collected at the end of each period and analyzed for the concentrations of phytoestrogens by using a liquid chromatography-tandem mass spectrometry technique. Concentration of total isoflavones was highest in ORG-SG and lowest in CON-TI silage, whereas the content of total lignans was highest in the grass silages. The isoflavones were extensively metabolized in the rumen on all diets, and the recovery of formononetin and daidzein in omasum, mainly as equol, averaged 0.11 mg/mg. The apparent intestinal metabolism was less severe as, on average, 0.29 mg/mg of the omasal flow was recovered in feces. The plant lignans were also strongly degraded in the rumen. However, the flow of lignans to omasum and excretion in feces were, on average, 7.2- and 5.2-fold higher, respectively, than the intake of the plant lignans

  17. Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2 cells treated with estradiol and phytoestrogens.

    PubMed

    Kelly, Lynne A; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; O'Leary, John J; Norris, Lucy A

    2014-01-15

    Phytoestrogens are popular alternatives to estrogen therapy however their effects on hemostasis in post-menopausal women are unknown. The aim of this study was to determine the effect of the phytoestrogens, genistein, daidzein and equol on the expression of key genes from the hemostatic system in human hepatocyte cell models and to determine the role of estrogen receptors in mediating any response seen. HepG2 cells and Hep89 cells (expressing estrogen receptor alpha (ERα)) were incubated for 24 h with 50 nM 17β-estradiol, genistein, daidzein or equol. Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), Factor VII, fibrinogen γ, protein C and protein S mRNA expression were determined using TaqMan PCR. Genistein and equol increased tPA and PAI-1 expression in Hep89 cells with fold changes greater than those observed for estradiol. In HepG2 cells (which do not express ERα), PAI-1 and tPA expression were unchanged. Increased expression of Factor VII was observed in phytoestrogen treated Hep89 cells but not in similarly treated HepG2s. Prothrombin gene expression was increased in equol and daidzein treated HepG2 cells in the absence of the classical estrogen receptors. These data suggest that phytoestrogens can regulate the expression of coagulation and fibrinolytic genes in a human hepatocyte cell line; an effect which is augmented by ERα.

  18. [Phytoestrogens--whether can they be an alternative to hormone replacement therapy for women during menopause period?].

    PubMed

    Dittfeld, Anna; Koszowska, Aneta; Brończyk, Anna Puzoń; Nowak, Justyna; Gwizdek, Katarzyna; Zubelewicz-Szkodzińska, Barbara

    2015-01-01

    Menopause is a turning point in a woman's life. Decreasing of secretion of estrogens can cause appearing of many health problems, which make that life is becoming harder in each partof life. Hormonal ReplacementTherapy (HRT) is using for relieving the symptoms of menopause, however, because of the possibility of adverse reactions cannot be used by all women. Alternative for HTC are phytoestrogens--compounds naturally occurring in plants, structurally similar to endogenous estrogen, so that they have an affinity for estrogen receptors, and in this way they can modulate functions of endocrine system. Phytoestrogens can play an important role in symptoms of menopause, but their positive impacts are being described for cardiovascular system, especially for lipid metabolism, bone metabolism. Moreover consumption of phytoestrogens could relieve as symptoms as: fatigue, insomnia, problems with concentrations and depression symptoms. Phytoestrogens are acting as antioxidants against free radicals, and reactive oxygen forms which are known as carcinogenic factors. Article is a review of the most important information about phitoestrogens and their influence on women organism during menopausal period.

  19. Are the phytoestrogens genistein and daidzein anti-herbivore defenses? A test using the gypsy moth (Lymantria dispar).

    PubMed

    Karowe, David Nathan; Radi, Joshua Karl

    2011-08-01

    Phytoestrogens are compounds that have moderate estrogenic or anti-estrogenic activity toward mammals. Although genistein and daidzein, the main phytoestrogens of soybean, have been the subject of thousands of studies that address their benefit to human health, relatively little is known about their benefits to plants that produce them. It has been suggested that genistein and daidzein protect plants against arthropod herbivores, but direct tests of this hypothesis are rare. In this study, we evaluated the effect of genistein and daidzein on the survivorship, growth, and fecundity of the gypsy moth, a generalist insect herbivore that does not encounter phytoestrogens in its normal diet. We compared survivorship, egg-to-pupa growth rate, and 4th instar performance of gypsy moth caterpillars on artificial diets containing no phytoestrogen, genistein, daidzein, or a combination of genistein and daidzein. Our results indicate that genistein and daidzein do not decrease survivorship, growth, or fecundity of this insect herbivore. Therefore, it seems unlikely that the primary function of these compounds in aboveground plant tissues is anti-herbivore defense.

  20. Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial.

    PubMed

    Riesco, Eléonor; Choquette, Stéphane; Audet, Mélisa; Lebon, Johann; Tessier, Daniel; Dionne, Isabelle J

    2012-02-01

    Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women. Nevertheless, the impact of their combination on adipokines and systemic inflammation was never investigated. The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women. Fifty-two obese women aged between 50 and 70 years were randomly assigned to (1) exercise with placebo (EX + PL; n = 25) or (2) exercise with phytoestrogens (EX + PHY; n = 27). Body weight, waist circumference, fat mass, and lean body mass (dual-energy x-ray absorptiometry) were assessed. Fasting plasma glucose and insulin, adiponectin, leptin, and C-reactive protein (CRP) levels were obtained after a 12-hour overnight fast. Total energy intake was measured with a 3-day dietary record. All measurements were performed before and after the 6-month intervention. Although energy intake remained unchanged, body composition was improved in all women (all Ps < .02). Plasma CRP and leptin levels decreased in both groups similarly (all Ps < .03), whereas plasma adiponectin and insulin did not change with exercise combined with placebo or phytoestrogens. Correlation analyses showed that homeostasis model assessment of insulin resistance (r = -0.58, P = .02) and fasting insulin levels (r = -0.42, P = .02) at baseline were both correlated with changes in leptin levels. Baseline fasting glucose (r = -0.36, P = .03) and adiponectin (r = 0.45, P = .005) levels were associated with changes in CRP concentrations. Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect, mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women.

  1. Silica nanoparticles induce reversible damage of spermatogenic cells via RIPK1 signal pathways in C57 mice

    PubMed Central

    Ren, Lihua; Zhang, Jin; Zou, Yang; Zhang, Lianshuang; Wei, Jialiu; Shi, Zhixiong; Li, Yanbo; Guo, Caixia; Sun, Zhiwei; Zhou, Xianqing

    2016-01-01

    The reproductive toxicity of silica nanoparticles (SiNPs) is well known, but the underlying mechanism is still not clear. To investigate the toxic mechanism of SiNPs on spermatogenic cells, 60 C57 male mice were randomly and equally divided into three groups (the control group, the saline control group, and the SiNPs group) with two observed time points (45 days and 75 days). The mice in the SiNPs group were administered with SiNPs 2 mg/kg diluted in normal saline, and the mice of the saline control group were given equivoluminal normal saline by tracheal perfusion every 3 days for 45 days (in total 15 times). The control group mice were bred without treatment. In each group, a half number of the mice were sacrificed on the 45th day after the first dose, and the remaining half were sacrificed on the 75th day. The results showed that SiNPs increased the malformation of sperms and decreased the motility and concentration of sperms in epididymis on the 45th day after the first dose. SiNPs induced oxidative stress in testis and led to apoptosis and necroptosis of the spermatogenic cells. Furthermore, SiNPs increased the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3 and RIPK3/MLKL on the 45th day after the first dose. However, compared with the saline control group, the index of sperms and the expression of Fas/FasL/RIPK1/FADD/caspase-8/caspase-3/RIPK3/MLKL showed no significant changes in the SiNPs group on the 75th day after the first dose. These data suggested that SiNPs could induce apoptosis and necroptosis in the spermatogenic cells by activating the RIPK1 pathway resulting from oxidative stress in male mice. SiNPs-induced damage recovered on the 75th day after the first dose, which suggested that SiNPs-induced toxicity is reversible. PMID:27307728

  2. Ultrastructural immunogold localization of major sperm protein (MSP) in spermatogenic cells of the nematode Acrobeles complexus (Nematoda, Rhabditida).

    PubMed

    Yushin, Vladimir V; Claeys, Myriam; Bert, Wim

    2016-10-01

    The nematode spermatozoa represent a highly modified (aberrant) type of male gametes that lack a flagellum but for which the process of spermatogenesis culminates in the production of a crawling spermatozoon on the basis of the cytoskeletal component known as "major sperm protein", or MSP. MSP is also known as an important hormone triggering oocyte maturation and ovulation in the model nematode Caenorhabditis elegans, where this protein was first identified. However, direct evidence of MSP localization and of its fate in nematode spermatogenic cells is rare. In this study, the spermatogenesis and sperm structure in the rhabditid nematode Acrobeles complexus (Rhabditida: Tylenchina: Cephalobomorpha: Cephaloboidea: Cephalobidae) has been examined with electron microscopy. Morphological observations were followed by high-pressure freezing and freeze-substitution fixation which allows post-embedding immunogold localization of MSP in all stages of sperm development using antibodies raised for MSP of C. elegans. In spermatocytes, synthetic activity results in the development of specific cellular components, fibrous bodies (FB) and membranous organelles (MO), which appear as FB-MO complexes where the filamentous matter of FB has been MSP-labeled. The spermatids subdivide into a residual body with superfluous cytoplasm, and a main cell body which contains nucleus, mitochondria and FB-MO complexes. These complexes dissociate into individual components, MO and FB, with the MSP being localized in FB. Immature spermatozoa from testes are opaque cells where a centrally located nucleus is surrounded by mitochondria, MO and FB clustered together, the MSP still being localized only in FB. Cytoplasm of mature spermatozoa from spermatheca is segregated into external pseudopods lacking organelles and a central cluster of mitochondria with intact MO surrounding the central nucleus. The FB ultimately disappear, and the MSP labeling becomes concentrated in the filamentous content of

  3. Ultrastructural immunogold localization of major sperm protein (MSP) in spermatogenic cells of the nematode Acrobeles complexus (Nematoda, Rhabditida).

    PubMed

    Yushin, Vladimir V; Claeys, Myriam; Bert, Wim

    2016-10-01

    The nematode spermatozoa represent a highly modified (aberrant) type of male gametes that lack a flagellum but for which the process of spermatogenesis culminates in the production of a crawling spermatozoon on the basis of the cytoskeletal component known as "major sperm protein", or MSP. MSP is also known as an important hormone triggering oocyte maturation and ovulation in the model nematode Caenorhabditis elegans, where this protein was first identified. However, direct evidence of MSP localization and of its fate in nematode spermatogenic cells is rare. In this study, the spermatogenesis and sperm structure in the rhabditid nematode Acrobeles complexus (Rhabditida: Tylenchina: Cephalobomorpha: Cephaloboidea: Cephalobidae) has been examined with electron microscopy. Morphological observations were followed by high-pressure freezing and freeze-substitution fixation which allows post-embedding immunogold localization of MSP in all stages of sperm development using antibodies raised for MSP of C. elegans. In spermatocytes, synthetic activity results in the development of specific cellular components, fibrous bodies (FB) and membranous organelles (MO), which appear as FB-MO complexes where the filamentous matter of FB has been MSP-labeled. The spermatids subdivide into a residual body with superfluous cytoplasm, and a main cell body which contains nucleus, mitochondria and FB-MO complexes. These complexes dissociate into individual components, MO and FB, with the MSP being localized in FB. Immature spermatozoa from testes are opaque cells where a centrally located nucleus is surrounded by mitochondria, MO and FB clustered together, the MSP still being localized only in FB. Cytoplasm of mature spermatozoa from spermatheca is segregated into external pseudopods lacking organelles and a central cluster of mitochondria with intact MO surrounding the central nucleus. The FB ultimately disappear, and the MSP labeling becomes concentrated in the filamentous content of

  4. Chemical studies of phytoestrogens and related compounds in dietary supplements: flax and chaparral.

    PubMed

    Obermeyer, W R; Musser, S M; Betz, J M; Casey, R E; Pohland, A E; Page, S W

    1995-01-01

    High-performance liquid chromatographic (HPLC) and mass spectrometric (MS) procedures were developed to determine lignans in flaxseed (Linum usitatissimum) and chaparral (Larrea tridentata). Flaxseed contains high levels of phytoestrogens. Chaparral has been associated with acute nonviral toxic hepatitis and contains lignans that are structurally similar to known estrogenic compounds. Both flaxseed and chaparral products have been marketed as dietary supplements. A mild enzyme hydrolysis procedure to prevent the formation of artifacts in the isolation step was used in the determination of secoisolariciresinol in flaxseed products. HPLC with ultraviolet spectral (UV) or MS detection was used as the determinative steps. HPLC procedures with UV detection and mass spectrometry were developed to characterize the phenolic components, including lignans and flavonoids, of chaparral and to direct fractionation studies for the bioassays.

  5. A critical view of the effects of phytoestrogens on hot flashes and breast cancer risk.

    PubMed

    This, Pascale; de Cremoux, Patricia; Leclercq, Guy; Jacquot, Yves

    2011-11-01

    The increased risk of breast cancer recently observed with some specific estro-progestin associations has raised concerns about the harmful effects of menopausal hormone replacement therapy (HRT). It has been proposed that phytoestrogens (PEs), which have a similar chemical structure to estrogens, could be used as HRT. The main selling points of these preparations concern the management of hot flashes and their potential beneficial effects on breast tissue. In this review, we will address the effects of PE on hot flashes and breast cancer risk as well as the questions raised on a chemical point of view. We conclude that the efficacy of a PE rich diet or nutritional supplements is not clearly established. The use of PE as an alternative for HRT cannot be advocated for now, due to insufficient and conflicting data on efficacy and safety. Moreover, due to the hormone dependence of breast cancer, PE use must be contraindicated in breast cancer survivors.

  6. Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown.

    PubMed

    Moreira, Ana C; Silva, Ana M; Santos, Maria S; Sardão, Vilma A

    2014-09-01

    Menopause is characterized by an altered hormonal status and by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, with increasing life span, women spend one-third of their lifetime under menopause. Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important topic in the clinic. This review describes physiological and hormone alterations observed during menopause and therapeutic strategies used during this period. We critically address the benefits and doubts associated with estrogen/progesterone-based hormone replacement therapy (HRT) and discuss the use of phytoestrogens (PEs) as a possible alternative. These relevant plant-derived compounds have structural similarities to estradiol, interacting with cell proteins and organelles, presenting several advantages and disadvantages versus traditional HRT in the context of menopause. However, a better assessment of PEs safety/efficacy would warrant a possible widespread clinical use.

  7. Development of a high-throughput LC/APCI-MS method for the determination of thirteen phytoestrogens including gut microbial metabolites in human urine and serum.

    PubMed

    Wyns, Ciska; Bolca, Selin; De Keukeleire, Denis; Heyerick, Arne

    2010-04-15

    The investigation into the potential usefulness of phytoestrogens in the treatment of menopausal symptoms requires large-scale clinical trials that involve rapid, validated assays for the characterization and quantification of the phytoestrogenic precursors and their metabolites in biological matrices, as large interindividual differences in metabolism and bioavailability have been reported. Consequently, a new sensitive high-performance liquid chromatography-mass spectrometry method (HPLC-MS) for the quantitative determination of thirteen phytoestrogens including their most important gut microbial metabolites (genistein, daidzein, equol, dihydrodaidzein, O-desmethylangolensin, coumestrol, secoisolariciresinol, matairesinol, enterodiol, enterolactone, isoxanthohumol, xanthohumol and 8-prenylnaringenin) in human urine and serum within one single analytical run was developed. The method uses a simple sample preparation procedure consisting of enzymatic deconjugation followed by liquid-liquid extraction (LLE) or solid-phase extraction (SPE) for urine or serum, respectively. The phytoestrogens and their metabolites are detected with a single quadrupole mass spectrometer using atmospheric pressure chemical ionization (APCI), operating both in the positive and the negative mode. This bioanalytical method has been fully validated and proved to allow an accurate and precise quantification of the targeted phytoestrogens and their metabolites covering the lower parts-per-billion range for the measurement of relevant urine and serum levels following ingestion of phytoestrogen-rich dietary supplements.

  8. Effects of phytoestrogens on growth-related and lipogenic genes in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Cleveland, Beth M; Manor, Meghan L

    2015-04-01

    This study determined whether estradiol (E2) or the phytoestrogens genistein and daidzein regulate expression of growth-related and lipogenic genes in rainbow trout. Juvenile fish (5 mon, 65.8±1.8 g) received intraperitoneal injections of E2, genistein, or daidzein (5 μg/g body weight) or a higher dose of genistein (50 μg/g body weight). Liver and white muscle were harvested 24h post-injection. In liver, expression of vitellogenin (vtg) and estrogen receptor alpha (era1) increased in all treatments and reflected treatment estrogenicity (E2>genistein (50 μg/g)>genistein (5 μg/g)=daidzein (5 μg/g)). Estradiol and genistein (50 μg/g) reduced components of the growth hormone (GH)/insulin-like growth factor (IGF) axis in liver, including increased expression of IGF binding protein-2b1 (igfbp2b1) and reduced igfbp5b1. In liver E2 and genistein (50 μg/g) affected expression of components of the transforming growth factor beta signaling mechanism, reduced expression of ppar and rxr transcription factors, and increased expression of fatty acid synthesis genes srebp1, acly, fas, scd1, and gpat and lipid binding proteins fabp3 and lpl. In muscle E2 and genistein (50 μg/g) increased era1 and erb1 expression and decreased erb2 expression. Other genes responded to phytoestrogens in a manner that suggested regulation by estrogen receptor-independent mechanisms, including increased ghr2, igfbp2a, igfbp4, and igfbp5b1. Expression of muscle regulatory factors pax7 and myod was increased by E2 and genistein. These data indicate that genistein and daidzein affect expression of genes in rainbow trout that regulate physiological mechanisms central to growth and nutrient retention.

  9. Effect of a 60-day oral gavage of a crude alkaloid extract from Chromolaena odorata leaves on hormonal and spermatogenic indices of male rats.

    PubMed

    Yakubu, Musa T

    2012-01-01

    The present study was aimed at investigating the effects of the crude alkaloids isolated from Chromolaena odorata leaves on the hormonal and spermatogenic indices of male rats. The alkaloids obtained from C odorata leaves using standard methods were administered to male rats for 60 days at the doses of 250, 500, and 1000 mg/kg body weight. Thin-layer chromatographic analysis of the alkaloid mixture produced 8 spots, 3 of which were alkaloids with R(f) values of 0.41, 0.49, and 0.55 as confirmed by the formation of orange color and creamy precipitates with both Dragendorff and Mayer reagents, respectively. The alkaloids were represented in the extract by a yield of 20.28 g, corresponding to a percentage yield of 90.05% of the total extract of 22.52 g. The final body weights of both the control and alkaloid-treated animals increased significantly (P < .05) compared with their respective body weights before treatment. The alkaloids significantly decreased (P < .05) the testes-body weight ratio; the concentrations of testicular total protein, glycogen, sialic acid, and cholesterol; and the activities of γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase. The serum luteinizing hormone and follicle-stimulating hormone levels, as well as testicular and serum testosterone levels, also decreased significantly (P < .05). There were decreases in the sperm count, motility, and density, as well as morphological changes in the sperm cells. The pH and whitish-gray color of the semen were not significantly affected. All of the doses of the alkaloids increased the total mean number of sperm cell abnormalities, with the secondary type predominating over the primary sperm cell abnormality. The alterations in the levels of the hormones and secretory and synthetic constituents of the testes and the spermatotoxic effects by the alkaloids from C odorata leaves may be due to nonavailability or deprivation of testosterone to the target organ. This lack of testosterone may

  10. A putative role for GnRH-II and its receptor in spermatogenic function of boars

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unlike the classical gonadotropin-releasing hormone (GnRH-I), the second mammalian isoform of GnRH (GnRH-II) is ubiquitously expressed with the most abundant transcript levels found in tissues outside of the hypothalamus. Moreover, GnRH-II is only an inefficient stimulator of gonadotropin release. I...

  11. Preventive effects of phytoestrogens against postmenopausal osteoporosis as compared to the available therapeutic choices: An overview

    PubMed Central

    Al-Anazi, Abdullah Foraih; Qureshi, Viquar Fatima; Javaid, Khalida; Qureshi, Shoeb

    2011-01-01

    Estrogen deficiency is a major risk factor for osteoporosis in postmenopausal women. Although hormone replacement therapy (HRT) has been rampantly used to recompense for the bone loss, but the procedure is coupled with severe adverse effects. Hence, there is a boost in the production of newer synthetic products to ward off the effects of menopause-related osteoporosis. As of today, there are several prescription products available for the treatment of postmenopause osteoporosis; most of these are estrogenic agents and combination products. Nevertheless, in view of the lack of effect and/or toxicity of these products, majority of the postmenopausal women are now fascinated by highly publicized natural products. This is an offshoot of the generalized consensus that these products are more effective and free from any adverse effects. Recently, certain plant-derived natural products, mostly phytoestrogens (isoflavones, lignans, coumestanes, stilbenes, flavonoids) and many more novel estrogen-like compounds in plants have been immensely used to prevent menopause-related depletion in bone mineral density (BMD). Although, a number of papers are published on menopause-related general symptoms, sexual dysfunction, cardiovascular diseases, Alzheimer's disease, diabetes, colon, and breast cancers, there is paucity of literature on the accompanying osteoporosis and its treatment. In view of the controversies on synthetic hormones and drugs and drift of a major population of patients toward natural drugs, it was found worthwhile to investigate if these drugs are suitable to be used in the treatment of postmenopausal osteoporosis. Preparation of this paper is an attempt to review the (a) epidemiology of postmenopausal osteoporosis, (b) treatment modalities of postmenopausal osteoporosis by hormones and synthetic drugs and the associated drawbacks and adverse effects, and (c) prevention and treatment of postmenopausal osteoporosis by phytoestrogens, their drawbacks and toxicity

  12. Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

    PubMed Central

    Zhang, Mingyue; Duan, Zhenghua; Wu, Yinghong; Liu, Zhen; Li, Ke; Wang, Lei

    2015-01-01

    Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256) collected from children in China were measured by liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S. PMID:26633438

  13. Argonaute2 Protein in Rat Spermatogenic Cells Is Localized to Nuage Structures and LAMP2-Positive Vesicles Surrounding Chromatoid Bodies.

    PubMed

    Fujii, Yuki; Onohara, Yuko; Fujita, Hideaki; Yokota, Sadaki

    2016-04-01

    Localization of Argonaute2 (AGO2) protein--an essential component for the processing of small interfering RNA (siRNA)-directed RNA interference (RNAi) in RNA-induced silencing complex (RISC) in nuage of rat spermatogenic cells--was evaluated by immunofluorescence microscopy (IFM) and immunoelectron microscopy (IEM). AGO2 was shown, for the first time, to be localized to four previously classified types of nuage: irregularly shaped perinuclear granules (ISPGs), intermitochondrial cement (IMC), satellite bodies (SBs), and chromatoid bodies (CBs). Dual IEM staining for AGO2/Maelstrom (MAEL) protein or AGO2/MIWI protein demonstrated that AGO2 is colocalized with MAEL or MIWI proteins in these types of nuage. Dual IFM and IEM staining of AGO2/lysosomal-associated membrane protein 2 (LAMP2) showed that CB in round spermatids are in contact with and surrounded by LAMP2-positive vesicles, whereas nuage in pachytene spermatocytes are not. Taken together, our findings indicate that: (i) AGO2 in pachytene spermatocytes functions in ISPGs, IMC, and SBs; (ii) AGO2 in round spermatids functions in CBs, and that CBs are associated with lysosomal compartments. PMID:27029769

  14. Fractionation of human spermatogenic cells using STA-PUT gravity sedimentation and their miRNA profiling.

    PubMed

    Liu, Yun; Niu, Minghui; Yao, Chencheng; Hai, Yanan; Yuan, Qingqing; Liu, Yang; Guo, Ying; Li, Zheng; He, Zuping

    2015-01-30

    Human spermatogenic cells have not yet been isolated, and notably, their global miRNA profiles remain unknown. Here we have effectively isolated human spermatogonia, pachytene spermatocytes and round spermatids using STA-PUT velocity sedimentation. RT-PCR, immunocytochemistry and meiosis spread assays revealed that the purities of isolated human spermatogonia, pachytene spermatocytes, and round spermatids were 90%, and the viability of these isolated cells was over 98%. MiRNA microarrays showed distinct global miRNA profiles among human spermatogonia, pachytene spermatocytes, and round spermatids. Thirty-two miRNAs were significantly up-regulated whereas 78 miRNAs were down-regulated between human spermatogonia and pachytene spermatocytes, suggesting that these miRNAs are involved in the meiosis and mitosis, respectively. In total, 144 miRNAs were significantly up-regulated while 29 miRNAs were down-regulated between pachytene spermatocytes and round spermatids, reflecting potential roles of these miRNAs in mediating spermiogenesis. A number of novel binding targets of miRNAs were further identified using various softwares and verified by real-time PCR. Our ability of isolating human spermatogonia, pachytene spermatocytes and round spermatids and unveiling their distinct global miRNA signatures and novel targets could provide novel small RNA regulatory mechanisms mediating three phases of human spermatogenesis and offer new targets for the treatment of male infertility.

  15. Cres2 and Cres3: new members of the cystatin-related epididymal spermatogenic subgroup of family 2 cystatins.

    PubMed

    Hsia, Nelson; Cornwall, Gail A

    2003-03-01

    The cystatin-related epididymal spermatogenic (CRES) and recently identified testatin and cystatin T proteins define a new subgroup within the family 2 cystatins of cysteine protease inhibitors. Members of the CRES subgroup are predominantly expressed in reproductive tissues and lack critical cystatin active-site sequences implying divergent functions. To determine whether there are additional members of the subgroup, we searched nucleotide databases and identified two novel genes that we designated Cres2 and Cres3. These genes, like other subgroup members, encode proteins with four conserved cysteine residues and predicted molecular weights characteristic of family 2 cystatins but have divergent cystatin inhibitory sequences. Furthermore, the genes exhibited reproductive-specific expression with Cres2 exclusively expressed in the epithelial cells of the proximal and midcaput epididymal regions and Cres3 expressed in the proximal caput epididymal epithelium, Sertoli cells of the testis, and early follicles and corpora lutea in the ovary. Additional studies showed that, like Cres, both Cres2 and Cres3 genes are dependent on testicular factors for epididymal expression. Taken together, CRES2 and CRES3 represent new members of a subgroup of cystatin family 2 proteins that likely carry out tissue-specific functions distinct from that of typical cystatins.

  16. Testis-Specific Y-Centric Protein-Protein Interaction Network Provides Clues to the Etiology of Severe Spermatogenic Failure.

    PubMed

    Ansari-Pour, Naser; Razaghi-Moghadam, Zahra; Barneh, Farnaz; Jafari, Mohieddin

    2016-03-01

    Pinpointing causal genes for spermatogenic failure (SpF) on the Y chromosome has been an ever daunting challenge with setbacks during the past decade. Since complex diseases result from the interaction of multiple genes and also display considerable missing heritability, network analysis is more likely to explicate an etiological molecular basis. We therefore took a network medicine approach by integrating interactome (protein-protein interaction (PPI)) and transcriptome data to reconstruct a Y-centric SpF network. Two sets of seed genes (Y genes and SpF-implicated genes (SIGs)) were used for network reconstruction. Since no PPI was observed among Y genes, we identified their common immediate interactors. Interestingly, 81% (N = 175) of these interactors not only interacted directly with SIGs, but also they were enriched for differentially expressed genes (89.6%; N = 43). The SpF network, formed mainly by the dys-regulated interactors and the two seed gene sets, comprised three modules enriched for ribosomal proteins and nuclear receptors for sex hormones. Ribosomal proteins generally showed significant dys-regulation with RPL39L, thought to be expressed at the onset of spermatogenesis, strongly down-regulated. This network is the first global PPI network pertaining to severe SpF and if experimentally validated on independent data sets can lead to more accurate diagnosis and potential fertility recovery of patients.

  17. Urinary phytoestrogen levels related to idiopathic male infertility in Chinese men.

    PubMed

    Xia, Yankai; Chen, Minjian; Zhu, Pengfei; Lu, Chuncheng; Fu, Guangbo; Zhou, Xiaojin; Chen, Daozhen; Wang, Honghua; Hang, Bo; Wang, Shoulin; Zhou, Zuomin; Sha, Jiahao; Wang, Xinru

    2013-09-01

    Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC-MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China.

  18. Effects of neonatal treatment with two phytoestrogens on male rat sexual behavior and partner preference.

    PubMed

    Morales-Otal, Adriana; Ferreira-Nuño, Armando; Olayo-Lortia, Jesús; Barrios-González, Javier; Tarragó-Castellanos, Rosario

    2016-10-01

    The aim of this work was to compare the effect of neonatal treatment with the phytoestrogens coumestrol (COU) and genistein (GEN), administered in equimolecular doses, on the sexual behavior and partner preference of male rats. Four groups of male rats were injected daily from day 1 to 5 with 150 µg of GEN, an equivalent amount of COU, 1 µg of β-estradiol 3-benzoato (EB), or olive oil (VEH) (control). A fifth group remained intact. In the GEN group, intromission and ejaculation latencies decreased, whereas ejaculatory frequency increased. Contrasting results were observed in COU males. EB males could not ejaculate and their mount and intromission latencies increased significantly. To determine sexual-partner preferences, a multiple partner preference arena was used and two types of tests were performed, the first one without allowing contact test (CT) with the stimulus animals, followed by a CT. COU and GEN groups did not show preference for any stimulus animal, whereas the EB males preferred the expert male. When CT with the stimulus animals was allowed, GEN-males preferred the receptive female, unlike the COU and EB groups. It is concluded that neonatal treatment with COU and GEN induced opposite effects, the effects of COU being more estrogenic.

  19. The phytoestrogen prunetin affects body composition and improves fitness and lifespan in male Drosophila melanogaster.

    PubMed

    Piegholdt, Stefanie; Rimbach, Gerald; Wagner, Anika E

    2016-02-01

    Dietary isoflavones, a group of secondary plant compounds that exhibit phytoestrogenic properties, are primarily found in soy. Prunetin, a representative isoflavone, was recently found to affect cell signaling in cultured cells; however, in vivo effects remain elusive. In this study, the model organism Drosophila melanogaster was used to investigate the effects of prunetin in vivo with respect to lifespan, locomotion, body composition, metabolism, and gut health. Adult flies were chronically administered a prunetin-supplemented diet. Prunetin improved median survival by 3 d, and climbing activity increased by 54% in males. In comparison with the females, male flies exhibited lower climbing activity, which was reversed by prunetin intake. Furthermore, prunetin-fed males exhibited increased expression of the longevity gene Sirtuin 1 (Sir2) (22%), as well as elevated AMPK activation (51%) and triglyceride levels (29%), whereas glucose levels decreased (36%). As females are long-lived compared with their male counterparts and exhibit higher triglyceride levels, prunetin apparently "feminizes" male flies via its estrogenicity. We conclude that the lifespan-prolonging effects of prunetin in the male fruit fly depend on changes in AMPK-regulated energy homeostasis via male "feminization." Collectively, we identified prunetin as a plant bioactive compound capable of improving health status and survival in male D. melanogaster. PMID:26538555

  20. Major isoflavonoid contents of the 1-year-cultivated phytoestrogen-rich herb, Pueraria mirifica.

    PubMed

    Cherdshewasart, Wichai; Sriwatcharakul, Suttijit

    2007-10-01

    Pueraria mirifica is a tuberous plant enriched with active phytoestrogens. There is no established information about the factors influencing isoflavonoid storage in the tubers. We investigated the tuberous storage of the major isoflavonoids of 1-year-old plants. Four cultivars of P. mirifica were cultivated in the same field trial during the same period to establish a unique plant age and differentiation under the same environment and soil conditions. The tubers collected from the 1-year-old plants in the summer, rainy season and winter were submitted to an HPLC analysis with a gradient system comprising 0.1% acetic acid and acetonitrile. Five major isoflavonoids, puerarin, daidzin, genistin, daidzein and genistein, were adopted as standards. P. mirifica tubers of different cultivars collected in the same season exhibited significant differences in individual and total isoflavonoid contents, showing chemovariety. P. mirifica tubers of the same cultivar collected from different seasons also exhibited significant differences in individual and total isoflavonoid contents, showing the influence of season. In conclusion, the tuberous storage of major isoflavonoids in 1-year-cultivated plants was greatly diverse and was strongly influenced by the season and plant genetics.

  1. Effects of neonatal treatment with two phytoestrogens on male rat sexual behavior and partner preference.

    PubMed

    Morales-Otal, Adriana; Ferreira-Nuño, Armando; Olayo-Lortia, Jesús; Barrios-González, Javier; Tarragó-Castellanos, Rosario

    2016-10-01

    The aim of this work was to compare the effect of neonatal treatment with the phytoestrogens coumestrol (COU) and genistein (GEN), administered in equimolecular doses, on the sexual behavior and partner preference of male rats. Four groups of male rats were injected daily from day 1 to 5 with 150 µg of GEN, an equivalent amount of COU, 1 µg of β-estradiol 3-benzoato (EB), or olive oil (VEH) (control). A fifth group remained intact. In the GEN group, intromission and ejaculation latencies decreased, whereas ejaculatory frequency increased. Contrasting results were observed in COU males. EB males could not ejaculate and their mount and intromission latencies increased significantly. To determine sexual-partner preferences, a multiple partner preference arena was used and two types of tests were performed, the first one without allowing contact test (CT) with the stimulus animals, followed by a CT. COU and GEN groups did not show preference for any stimulus animal, whereas the EB males preferred the expert male. When CT with the stimulus animals was allowed, GEN-males preferred the receptive female, unlike the COU and EB groups. It is concluded that neonatal treatment with COU and GEN induced opposite effects, the effects of COU being more estrogenic. PMID:27482864

  2. Phytoestrogens and mycoestrogens in surface waters--Their sources, occurrence, and potential contribution to estrogenic activity.

    PubMed

    Jarošová, Barbora; Javůrek, Jakub; Adamovský, Ondřej; Hilscherová, Klára

    2015-08-01

    This review discusses the potential contribution of phytoestrogens and mycoestrogens to in vitro estrogenic activities occurring in surface waters and in vivo estrogenic effects in fish. Main types, sources, and pathways of entry into aquatic environment of these detected compounds were summarized. Reviewed concentrations of phyto/mycoestrogens in surface waters were mostly undetectable or in low ng/L ranges, but exceeded tens of μg/L for the flavonoids biochanin A, daidzein and genistein at some sites. While a few phytosterols were reported to occur at relatively high concentrations in surface waters, information about their potencies in in vitro systems is very limited, and contradictory in some cases. The relative estrogenic activities of compounds (compared to standard estrogen 17β-estradiol) by various in vitro assays were included, and found to differ by orders of magnitude. These potencies were used to estimate total potential estrogenic activities based on chemical analyses of phyto/mycoestrogens. In vivo effective concentrations of waterborne phyto/mycoestrogens were available only for biochanin A, daidzein, formononetin, genistein, equol, sitosterol, and zearalenone. The lowest observable effect concentrations in vivo were reported for the mycoestrogen zearalenone. This compound and especially its metabolites also elicited the highest in vitro estrogenic potencies. Despite the limited information available, the review documents low contribution of phyto/mycoestrogens to estrogenic activity in vast majority of surface waters, but significant contribution to in vitro responses and potentially also to in vivo effects in areas with high concentrations.

  3. [Spermatogenic function under the influence of heavy metal salts and its correction by preparation Tivortin].

    PubMed

    Romaniuk, A M; Sauliak, S V; Moskalenko, R A; Moskalenko, Iu V

    2012-01-01

    Entrance of threshold concentrations of copper, zinc, iron, manganese, lead, chromium into the body of sexually mature male rats leads to secretory malfunction of the testicles, which manifests by a decrease of sperm concentration in the ejaculate, a decrease of percentage of motile gametes, an increase in the proportion of morphologically abnormal sperm forms. The evidence of disorders in spermatogram's parameters is directly depends on the duration of the influence of combination of heavy metal salts. The application of the drug Tivortin against intoxication of heavy metal salts decrease the adverse movement of quantitative and qualitative parameters of rat's spermatogramms, so far as Tivortin improves blood circulation, stimulates cell proliferation and cell differentiation, inhibits oxidative apoptosis. These explain beneficial effects of the drug on the growth and maturation of germ cells in case of the influence heavy metal salts combination on organ and the whole body. PMID:23035612

  4. Dose-response effects of phytoestrogens on the activity and expression of 3beta-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells.

    PubMed

    Lacey, Michael; Bohday, Jemma; Fonseka, Shamara M R; Ullah, Amer I; Whitehead, Saffron A

    2005-08-01

    There is evidence that certain phytoestrogens can inhibit key steroidogenic enzymes although most studies have been carried out on microsomal or purified enzyme preparations, some using cell lines. This study was designed to test the hypothesis that low doses of phytoestrogens, at concentrations that would be attained through the diet, could inhibit 3beta-hydroxysteroid dehydrogenase (HSD) and/or aromatase in primary cultures of human granulosa-luteal (GL) cells and that this effect was due to a decrease in the expression of these proteins. Based on published evidence, eight compounds were selected for investigation and these included the flavones apigenin and quercetin, the isoflavones genistein, biochanin A and daidzein, the lignans, enterodiol and enterolactone, and the mycotoxin zearalenone. Human GL cells were cultured for 48 h in the presence of these phytoestrogens at concentrations ranging from 0.01 to 100 microM and after addition of fresh media the conversion of pregnenolone to progesterone or androstenedione to oestradiol over a 4h period was measured. Biochanin A was the only phytoestrogen that displayed any dose-dependent inhibition of 3beta-HSD, others showing inhibition at doses >/=10 microM. Apigenin and quercetin only inhibited aromatase/17beta-HSD at high doses as did genistein, biochanin A and daidzein. The lignans had weak inhibitory effects on aromatase/17beta-HSD, whilst zearalenone showed potent inhibition at 0.1 microM. Phytoestrogens did not exert any significant effects on protein expression of 3beta-HSD or aromatase as determined by Western blots. It is concluded that steroidogenic enzymes are inhibited by phytoestrogens in primary cultures of human GL cells but these cells are less sensitive to the effects of phytoestrogens than cell-free systems. This may be due to poor lipid solubility or cellular metabolism. We have also shown for the first time that phytoestrogens do not act by inhibiting the cellular concentration of 3beta-HSD and

  5. Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study.

    PubMed

    Atteritano, Marco; Pernice, Francesco; Mazzaferro, Susanna; Mantuano, Stefania; Frisina, Alessia; D'Anna, Rosario; Cannata, Maria Letizia; Bitto, Alessandra; Squadrito, Francesco; Frisina, Nicola; Buemi, Michele

    2008-07-28

    To evaluate in a twelve-month, randomized placebo-controlled study whether pure administration of phytoestrogen genistein (54 mg/day) might reduce cytogenetic biomarkers in peripheral lymphocytes of postmenopausal women. A total of 57 postmenopausal women met the criteria and were randomly assigned to receive phytoestrogen genistein (n = 30) or placebo (n = 27). There was no significant difference in age, length of time since menopause or body mass index between the two groups. After one year, plasma genistein level was 0.14 +/- 0.01 micromol/L in the control group and 0.72 +/- 0.08 micromol/L in the genistein group (P < 0.0001). At baseline, sister chromatid exchange rate was 4.97 +/- 2.17 in the control group and 4.96 +/- 1.83 in the genistein group (P = 0.89). After one year, sister chromatid exchange rate was 4.96 +/- 2.16 in the control group and 3.98 +/- 1.14 in the genistein group (P < 0.05). High frequency cells count was 3% in the genistein group and 5% in the control group (P < 0.05) at the end of the study. Chromosomal aberration frequency was 5.55% in the control group at time 0 and 5.75% in the genistein group; after one year, the figures were 5.86% in the control group and 4.5% in the genistein group (P < 0.05). After one year, there was a negative relationship between sister chromatid exchange rate and plasma levels (r = - 0.43; P < 0.05) in the genistein group. Phytoestrogen genistein has been shown in postmenopausal women to be effective in the reduction of cytogenetic biomarkers. The protective effect on genomic damage appears to be a particularly promising tool in reducing the risk of cancer.

  6. Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study

    PubMed Central

    Ambiye, Vijay R.; Dongre, Swati; Aptikar, Pradnya; Kulkarni, Madhura; Dongre, Atul

    2013-01-01

    Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment (n = 21) with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo (n = 25) in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; P < 0.0001), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; P < 0.0001), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; P < 0.0001) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility. PMID:24371462

  7. The phytoestrogen genistein enhances osteogenesis and represses adipogenic differentiation of human primary bone marrow stromal cells.

    PubMed

    Heim, M; Frank, O; Kampmann, G; Sochocky, N; Pennimpede, T; Fuchs, P; Hunziker, W; Weber, P; Martin, I; Bendik, I

    2004-02-01

    In the present study, we investigated the role of the phytoestrogen genistein and 17beta-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-alpha, -beta1, -beta2, -beta3, -beta4, -beta5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-alpha1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor gamma (PPARgamma) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-kappaB ligand gene expression ratio, and the expression of TGFbeta1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARgamma and CCAAT/enhancer-binding protein-alpha at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFbeta1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFbeta1 pathway abolished the effects of genistein on PPARgamma protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17beta-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFbeta1 signaling. PMID:14605006

  8. The Phytoestrogen Genistein Affects Breast Cancer Cells Treatment Depending on the ERα/ERβ Ratio.

    PubMed

    Pons, Daniel Gabriel; Nadal-Serrano, Mercedes; Torrens-Mas, Margalida; Oliver, Jordi; Roca, Pilar

    2016-01-01

    Genistein (GEN) is a phytoestrogen found in soybeans. GEN exerts its functions through its interaction with the estrogen receptors (ER), ERα and ERβ, and we previously reported that the ERα/ERβ ratio is an important factor to consider in GEN-treated breast cancer cells. The aim of this study was to investigate the effects of GEN in breast cancer cells with different ERα/ERβ ratio: MCF-7 (high ratio), T47D (low ratio), and MCF-7 overexpressing ERβ (MCF7 + ERβ) treated with cisplatin (CDDP), paclitaxel (PTX) or tamoxifen (TAM). Cell viability, ROS production, autophagy, apoptosis, antioxidant enzymes protein levels, and cell cycle were analyzed. GEN treatment provoked an increase in cell viability in MCF-7 cells and in the antioxidant enzymes protein levels in combination with the cytotoxic agents, decreasing ROS production (CDDP + GEN and TAM+GEN) and autophagy (TAM + GEN) or apoptosis (CDDP + GEN and TAM + GEN). Moreover GEN treatment enhanced the cell cycle S phase entry in CDDP+GEN- and TAM + GEN-treated MCF-7 cells and, in the case of CDDP + GEN, increased the proportion of cells in the G2/M phase and decreased it in the subG0 /G1 phase. Otherwise, in the T47D and MCF7 + ERβ cells the combination of GEN with cytotoxic treatments did not cause significant changes in these parameters, even TAM + GEN-treated T47D cells showed less cell viability due to an increment in the autophagy. In conclusion, GEN consumption may be counterproductive in those patients receiving anticancer treatment with a high ERα/ERβ ratio diagnosed breast cancer and it could be harmless or even beneficial in those patients with a lower ERα/ERβ ratio breast cancer cells.

  9. Vitamin A Deprivation Affects the Progression of the Spermatogenic Wave and Initial Formation of the Blood-testis Barrier, Resulting in Irreversible Testicular Degeneration in Mice

    PubMed Central

    CHIHARA, Masataka; OTSUKA, Saori; ICHII, Osamu; KON, Yasuhiro

    2013-01-01

    Abstract The blood testis-barrier (BTB) is essential for maintaining homeostasis in the seminiferous epithelium. Although many studies have reported that vitamin A (VA) is required for the maintenance of spermatogenesis, the relationships between the BTB, spermatogenesis and VA have not been elucidated. In this study, we analyzed BTB assembly and spermatogenesis in the testes of mice fed the VA-deficient (VAD) diet from the prepubertal period to adulthood. During the prepubertal period, no changes were observed in the initiation and progression of the first spermatogenic wave in mice fed the VAD diet. However, the numbers of preleptotene/leptotene spermatocytes derived from the second spermatogenic wave onwards were decreased, and initial BTB formation was also delayed, as evidenced by the decreased expression of mRNAs encoding BTB components and VA signaling molecules. From 60 days postpartum, mice fed the VAD diet exhibited apoptosis of germ cells, arrest of meiosis, disruption of the BTB, and dramatically decreased testis size. Furthermore, vacuolization and calcification were observed in the seminiferous epithelium of adult mice fed the VAD diet. Re-initiation of spermatogenesis by VA replenishment in adult mice fed the VAD diet rescued BTB assembly after when the second spermatogenic wave initiated from the arrested spermatogonia reached the preleptotene/leptotene spermatocytes. These results suggested that BTB integrity was regulated by VA metabolism with meiotic progression and that the impermeable BTB was required for persistent spermatogenesis rather than meiotic initiation. In conclusion, consumption of the VAD diet led to critical defects in spermatogenesis progression and altered the dynamics of BTB assembly. PMID:23934320

  10. Altered miRNA Signature of Developing Germ-cells in Infertile Patients Relates to the Severity of Spermatogenic Failure and Persists in Spermatozoa

    PubMed Central

    Muñoz, Xavier; Mata, Ana; Bassas, Lluís; Larriba, Sara

    2015-01-01

    The aim of this study was to assess the cellular miRNA expression behaviour in testes with spermatogenic failure (SpF). We performed a high-throughput screen of 623 mature miRNAs by a quantitative RT-qPCR-based approach in histologically well-defined testicular samples with spermatogenic disruption at different germ-cell stages, which revealed altered patterns of miRNA expression. We focussed on the differentially expressed miRNAs whose expression correlated with the number of testicular mature germ-cells and described the combined expression values of a panel of three miRNAs (miR-449a, miR-34c-5p and miR-122) as a predictive test for the presence of mature germ-cells in testicular biopsy. Additionally, we determined decreased cellular miRNA content in developing germ-cells of SpF testis; this was more noticeable the earlier the stage of germ-cell differentiation was affected by maturation failure. Furthermore, we showed that the miRNA expression profile in mature sperm from mild SpF patients was widely altered. Our results suggest that the cellular miRNA content of developed germ-cells depends heavily on the efficacy of the spermatogenic process. What is more, spermatozoa that have fulfilled the differentiation process still retain the dysregulated miRNA pattern observed in the developing SpF germ-cells. This altered miRNA molecular signature may have functional implications for the male gamete. PMID:26648257

  11. Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells.

    PubMed

    Seo, Hye-Sook; Ju, Ji-Hyun; Jang, Kibeom; Shin, Incheol

    2011-02-01

    In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-MB-231) estrogen receptor α (ERα)-negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ERα-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ERα-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ERα-negative breast cancer.

  12. Phytoestrogenic effects of black tea extract (Camellia sinensis) in an oophorectomized rat (Rattus norvegicus) model of osteoporosis.

    PubMed

    Das, Asankur Sekhar; Das, Dolan; Mukherjee, Maitrayee; Mukherjee, Sandip; Mitra, Chandan

    2005-10-28

    The adverse side effects of currently available anti-osteoporotic agents warrant the search for compounds with less toxic effects. In this study, we assessed the phytoestrogenic potentiality of whole aqueous extract of black tea (BTE) in a bilaterally oophorectomized rat model (2.5%, 1 ml/100 g body weight/day for 28 days). Although the supplementation was given for 28 days but, sign of revival of copulation period (estrous stage) from non-receptive diestrous stage was first noticed after 21 days of BTE supplementation in bilaterally oophorectomized rats. This was accompanied by a significant increase in serum estradiol level. To test whether this increase in serum estradiol level could have an influence upon the oophorectomy-induced damage of bone, we assessed marker parameters of bone resorption and osteoclastic activity (tartrate-resistant acid phosphatase), collagen degradation (urinary hydroxyproline), bone loss (bone ash mineral content) and bone breaking strength (bone density). Results indicated that increase in serum estradiol level after BTE supplementation could significantly diminish oophorectomy-induced decaying changes in bone. This study proposes that aqueous BTE may be assessed as a phytoestrogenic compound for prevention against estrogen deficiency-related osteoporotic damages.

  13. Phytoestrogens regulate the proliferation and expression of stem cell factors in cell lines of malignant testicular germ cell tumors.

    PubMed

    Hasibeder, Astrid; Venkataramani, Vivek; Thelen, Paul; Radzun, Heinz-Joachim; Schweyer, Stefan

    2013-11-01

    Phytoestrogens have been shown to exert anti-proliferative effects on different cancer cells. In addition it could be demonstrated that inhibition of proliferation is associated with downregulation of the known stem cell factors NANOG, POU5F1 and SOX2 in tumor cells. We demonstrate the potential of Belamcanda chinensis extract (BCE) and tectorigenin as anticancer drugs in cell lines of malignant testicular germ cell tumor cells (TGCT) by inhibition of proliferation and regulating the expression of stem cell factors. The TGCT cell lines TCam-2 and NTera-2 were treated with BCE or tectorigenin and MTT assay was used to measure the proliferation of tumor cells. In addition, the expression of stem cell factors was analyzed by quantitative PCR and western blot analysis. Furthermore, global expression analysis was performed by microarray technique. BCE and tectorigenin inhibited proliferation and downregulated the stem cell factors NANOG and POU5F1 in TGCT cells. In addition, gene expression profiling revealed induction of genes important for the differentiation and inhibition of oncogenes. Utilizing connectivity map in an attempt to elucidate mechanism underlying BCE treatments we found highly positive association to histone deacetylase inhibitors (HDACi) amongst others. Causing no histone deacetylase inhibition, the effects of BCE on proliferation and stem cell factors may be based on histone-independent mechanisms such as direct hyperacetylation of transcription factors. Based on these findings, phytoestrogens may be useful as new agents in the treatment of TGCT.

  14. Development of an updated phytoestrogen database for use with the SWAN food frequency questionnaire: intakes and food sources in a community-based, multiethnic cohort study.

    PubMed

    Huang, Mei-Hua; Norris, Jean; Han, Weijuan; Block, Torin; Gold, Ellen; Crawford, Sybil; Greendale, Gail A

    2012-01-01

    Phytoestrogens, heterocyclic phenols found in plants, may benefit several health outcomes. However, epidemiologic studies of the health effects of dietary phytoestrogens have yielded mixed results, in part due to challenges inherent in estimating dietary intakes. The goal of this study was to improve the estimates of dietary phytoestrogen consumption using a modified Block Food Frequency Questionnaire (FFQ), a 137-item FFQ created for the Study of Women's Health Across the Nation (SWAN) in 1994. To expand the database of sources from which phytonutrient intakes were computed, we conducted a comprehensive PubMed/Medline search covering January 1994 through September 2008. The expanded database included 4 isoflavones, coumestrol, and 4 lignans. The new database estimated isoflavone content of 105 food items (76.6%) vs. 14 (10.2%) in the 1994 version and computed coumestrol content of 52 food items (38.0%), compared to 1 (0.7%) in the original version. Newly added were lignans; values for 104 FFQ food items (75.9%) were calculated. In addition, we report here the phytonutrient intakes for each racial and language group in the SWAN sample and present major food sources from which the phytonutrients came. This enhanced ascertainment of phytoestrogens will permit improved studies of their health effects.

  15. Comparative effects of soy phytoestrogens and 17β-estradiol on DNA methylation of a panel of 24 genes in prostate cancer cell lines.

    PubMed

    Adjakly, Mawussi; Ngollo, Marjolaine; Lebert, André; Dagdemir, Aslihan; Penault-Llorca, Frédérique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2014-01-01

    Major phytoestrogens genistein and daidzein have been reported to have the ability to reverse DNA methylation in cancer cell lines. The mechanism by which genistein and daidzein have an inhibiting action on DNA methylation is not well understood. The aim of this study was to investigate the effects of soy phytoestrogens and the natural estrogen 17β-estradiol (E2) to determine whether one of the estrogen receptors is mobilized for the action of these compounds on DNA methylation. We also made a comparative study with a DNA methylation inhibitor (5-azacytidine) and a DNA methylation activator (budesonide). Three prostate cell lines, PC-3, DU-145, and LNCaP, were treated with 40 μM genistein, 110 μM daidzein, 2 μM budesonide, 2 μM 5-azacytidine, and 10 μM E2. In these 3 human prostate cancer cell lines, we performed methylation quantification using methyl-profiler-DNA-methylation analysis. Soy phytoestrogens and E2 induced a demethylation of all the promoter regions studied except for those that were unmethylated in control cells. Our results showed that E2 induces, like soy phytoestrogen, a decrease in DNA methylation in prostate cancer cell lines. This action may be mediated through ERβ.

  16. Influence of partial replacement of soya bean meal by faba beans or peas in heavy pigs diet on meat quality, residual anti-nutritional factors and phytoestrogen content.

    PubMed

    Gatta, Domenico; Russo, Claudia; Giuliotti, Lorella; Mannari, Claudio; Picciarelli, Piero; Lombardi, Lara; Giovannini, Luca; Ceccarelli, Nello; Mariotti, Lorenzo

    2013-06-01

    The study evaluated the partial substitution of soybean meal by faba beans (18%) or peas (20%) as additional protein sources in diets destined for typical Italian heavy pig production. It compared animal performances, meat quality, the presence of residual anti-nutritional factors (ANF) and phytoestrogens in plasma and meat and the possible effects on pig health, by evaluating oxidative, inflammatory and pro-atherogenic markers. The results showed that the productive performances, expressed as body weight and feed conversion ratio, of pigs fed with faba bean and pea diets were similar to those of pigs fed only the soybean meal. Meat quality of pigs fed with the three diets was similar in colour, water-holding capacity, tenderness and chemical composition. Despite the higher levels of phytoestrogen in the plasma of pigs fed only the soybean meal, phytoestrogen concentration in the muscle was equivalent to that of animals fed diets with faba beans, whereas pigs fed a diet with peas showed a lower concentration. Inflammation and pro-atherogenic parameters did not show significant differences among the three diets. Overall, the partial substitution of soybean meal by faba beans appears more interesting than with peas, particularly in relation to the higher amount of polyphenols in the diet and the highest concentration of phytoestrogens found in the plasma and muscle of animals, while the pyrimidine anti-nutritional compounds present in the diet did not appear to accumulate and had no effect on the growth performance of animals.

  17. Phytoestrogens directly inhibit TNF-α-induced bone resorption in RAW264.7 cells by suppressing c-fos-induced NFATc1 expression.

    PubMed

    Karieb, Sahar; Fox, Simon W

    2011-02-01

    TNF-α-induced osteoclastogenesis is central to post-menopausal and inflammatory bone loss, however, the effect of phytoestrogens on TNF-α-induced bone resorption has not been studied. The phytoestrogens genistein, daidzein, and coumestrol directly suppressed TNF-α-induced osteoclastogenesis and bone resorption. TRAP positive osteoclast formation and resorption area were significantly reduced by genistein (10(-7)  M), daidzein (10(-5)  M), and coumestrol (10(-7)  M), which was prevented by the estrogen antagonist ICI 182,780. TRAP expression in mature TNF-α-induced osteoclasts was also significantly reduced by these phytoestrogen concentrations. In addition, in the presence of ICI 182,780 genistein and coumestrol (10(-5) -10(-6)  M) augmented TNF-α-induced osteoclast formation and resorption. However, this effect was not observed in the absence of estrogen antagonist indicating that genistein's and coumestrol's ER-dependent anti-osteoclastic action normally negates this pro-osteoclastic effect. To determine the mechanism mediating the anti-osteoclastic action we examined the effect of genistein, coumestrol, and daidzein on caspase 3/7 activity, cell viability and expression of key genes regulating osteoclast differentiation and fusion. While anti-osteoclastic phytoestrogen concentrations had no effect on caspase 3/7 activity or cell viability they did significantly reduce TNF-α-induced c-fos and NFATc1 expression in an ER dependent manner and also inhibited NFATc1 nuclear translocation. Significant decreases in NFκB and DC-STAMP levels were also noted. Interestingly, constitutive c-fos expression prevented the anti-osteoclastic action of phytoestrogens on differentiation, resorption and NFATc1. This suggests that phytoestrogens suppress TNF-α-induced osteoclastogenesis via inhibition of c-fos-dependent NFATc1 expression. Our data provides further evidence that phytoestrogens have a potential role in the treatment of post-menopausal and inflammatory

  18. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model

    SciTech Connect

    Duursen, Majorie B.M. van; Smeets, Evelien E.J.W.; Rijk, Jeroen C.W.; Nijmeijer, Sandra M.; Berg, Martin van den

    2013-06-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. - Highlights: • Supplements containing phytoestrogens are commonly used by women with breast cancer. • Phytoestrogens alter steroidogenesis in a co-culture breast

  19. Hormonal concentrations and reproductive performance of Holstein heifers fed Trifolium alexandrinum as a phytoestrogenic roughage.

    PubMed

    Hashem, N M; El-Azrak, K M; Sallam, S M A

    2016-07-01

    Effects of phytoestrogen isoflavones in Berseem clover on hormonal balance during early pregnancy and fertility of heifers were studied. Holstein heifers (n=26) were divided into two equal homogenous groups. Heifers in the first group (Clover-fed group) were fed Egyptian clover (Trifolium alexandrinum) as oestrogenic roughage; whereas the heifers in the second group (Silage-fed group) were fed maize silage. Concentrations of four isoflavone aglycones (genistein. Daidzein, biochanin A and formononetein) were determined in the two roughages. Treatment lasted for 20 consecutive weeks (5 months) during which blood samples were collected biweekly for determining the metabolic profile of heifers. Heifers were subjected to oestrous synchronisation using a double prostaglandin F2α (PGF2α) based protocol, 14days apart (week 10 and 12), and were artificially inseminated 12h following detection of overt signs of oestrus. Concentrations of serum oestradiol (E2) and progesterone (P4) on the day of insemination (Day 0) and on Days 7, 14 and 21 post-insemination (early pregnancy) were determined and P4 to E2 ratio was calculated. Clover had greater total isoflavone content than maize silage. The dominant isoflavone detected in Berseem clover was biochanin A, whereas the least was formononetein. Metabolic profile was not affected (P>0.05) by the type of roughage and was in the same trend in both experimental groups. The overall mean concentration of serum E2 was greater (P<0.05) in the clover-fed group than in the silage-fed group. The overall mean concentration of serum P4 was less (P<0.05) in the clover-fed group than in the silage-fed group. During the period of early pregnancy (from Day 7-21 post-insemination) the concentration of serum P4 increased in the silage-fed group, however, no change was observed in the clover-fed group. The overall mean of P4 to E2 ratio was greater (P<0.001) in the silage-fed group compared with that in the clover-fed group. Heifers fed clover had

  20. Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison

    SciTech Connect

    Charles, Grantley D. . E-mail: charles_grantley@allergan.com; Gennings, Chris; Tornesi, Belen; Kan, H. Lynn; Zacharewski, Timothy R.; Bhaskar Gollapudi, B.; Carney, Edward W.

    2007-02-01

    In the evaluation of chemical mixture toxicity, it is desirable to develop an evaluation paradigm which incorporates some critical attributes of real world exposures, particularly low dose levels, larger numbers of chemicals, and chemicals from synthetic and natural sources. This study evaluated the impact of low level exposure to a mixture of six synthetic chemicals (SC) under conditions of co-exposure to various levels of plant-derived phytoestrogen (PE) compounds. Estrogenic activity was evaluated using an in vitro human estrogen receptor (ER) transcriptional activation assay and an in vivo immature rat uterotrophic assay. Initially, dose-response curves were characterized for each of the six SCs (methoxyclor, o,p-DDT, octylphenol, bisphenol A, {beta}-hexachlorocyclohexane, 2,3-bis(4-hydroxyphenyl)-propionitrile) in each of the assays. The six SCs were then combined at equipotent ratios and tested at 5-6 dose levels spanning from very low, sub-threshold levels, to a dose in which every chemical in the mixture was at its individual estrogenic response threshold. The SC mixtures also were tested in the absence or presence of 5-6 different levels of PEs, for a total of 36 (in vitro) or 25 (in vivo) treatment groups. Both in vitro and in vivo, low concentrations of the SC mixture failed to increase estrogenic responses relative to those induced by PEs alone. However, significant increases in response occurred when each chemical in the SC mixture was near or above its individual response threshold. In vitro, interactions between high-doses of SCs and PEs were greater than additive, whereas mixtures of SCs in the absence of PEs interacted in a less than additive fashion. In vivo, the SC and PE mixture responses were consistent with additivity. These data illustrate a novel approach for incorporating key attributes of real world exposures in chemical mixture toxicity assessments, and suggest that chemical mixture toxicity is likely to be of concern only when the

  1. Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens, in urine of women on various habitual diets.

    PubMed

    Adlercreutz, H; Fotsis, T; Bannwart, C; Wähälä, K; Mäkelä, T; Brunow, G; Hase, T

    1986-11-01

    Recently two groups of compounds with diphenolic structure, the lignans and the isoflavonic phytoestrogens, were detected and identified in human urine and other biological fluids. These compounds are of great biological interest because they exhibit both in vitro and in vivo weak estrogenic and sometimes also antiestrogenic activities and many plant lignans have been shown to have anticarcinogenic, antiviral, antifungal and other interesting biological effects. The compounds found in relatively large amounts (10-1000 times more than estrogens) in urine are modified by intestinal bacteria from plant lignans and phytoestrogens, which are present in fiber-rich food such as grain and beans. They bind with low affinity to estrogen receptors and preliminary results suggest that they may induce production of sex hormone binding globulin (SHBG) in the liver and in this way may influence sex hormone metabolism and biological effects. Five compounds, the lignans enterolactone (Enl), enterodiol (End) and the isoflavonic phytoestrogen metabolites daidzein (Da), equol (Eq) and O-desmethylangolensin (O-Dma) were measured in urine by gas chromatography-mass spectrometry (selected ion monitoring) using deuterated internal standards in 5 groups of women (total number 53). The members of three dietary groups (omnivores, lactovegetarians and macrobiotics) were living in Boston and of two groups in Helsinki (omnivores and lactovegetarians). Until now measurements have been carried out in 94 72-h samples. The highest mean excretion of the most abundant compound, enterolactone, was found in the macrobiotic group and the lowest in the omnivoric groups. Total mean 24-h excretion of enterolactone was 17,680 nmol in the macrobiotics, 4,170 nmol in the Boston lactovegetarians, 3,650 nmol in the Helsinki lactovegetarians, 2,460 nmol in the Helsinki omnivores and 2,050 nmol in the Boston omnivores. The other diphenols followed approximately the same pattern. In an earlier study the lowest

  2. Comparison of the effects of mesquite pod and Leucaena extracts with phytoestrogens on the reproductive physiology and sexual behavior in the male rat.

    PubMed

    Retana-Márquez, S; Juárez-Rojas, L; Hernández, A; Romero, C; López, G; Miranda, L; Guerrero-Aguilera, A; Solano, F; Hernández, E; Chemineau, P; Keller, M; Delgadillo, J A

    2016-10-01

    Mesquite (Prosopis sp.) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E2) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E2; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E2. The main disruptor of sexual behavior was E2, however after 40 and 50days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E2. The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in Leucaena extract and E2 groups, but not in mesquite- and phytoestrogens-treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E2

  3. Comparison of the effects of mesquite pod and Leucaena extracts with phytoestrogens on the reproductive physiology and sexual behavior in the male rat.

    PubMed

    Retana-Márquez, S; Juárez-Rojas, L; Hernández, A; Romero, C; López, G; Miranda, L; Guerrero-Aguilera, A; Solano, F; Hernández, E; Chemineau, P; Keller, M; Delgadillo, J A

    2016-10-01

    Mesquite (Prosopis sp.) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E2) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E2; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E2. The main disruptor of sexual behavior was E2, however after 40 and 50days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E2. The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in Leucaena extract and E2 groups, but not in mesquite- and phytoestrogens-treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E2

  4. Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women

    PubMed Central

    Myasoedova, Veronika A.; Kirichenko, Tatyana V.; Melnichenko, Alexandra A.; Orekhova, Varvara A.; Ravani, Alessio; Poggio, Paolo; Sobenin, Igor A.; Bobryshev, Yuri V.; Orekhov, Alexander N.

    2016-01-01

    The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT) for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6) were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT) were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011) and by 5.2% in placebo recipients (p = 0.020); low density lipoprotein (LDL) cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040) and by 5.2% in placebo recipients (non-significant, NS); high density lipoprotein (HDL) cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS) and by 4.5% in placebo recipients (p = 0.038); triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS) and by 7.1% in

  5. Anti-Atherosclerotic Effects of a Phytoestrogen-Rich Herbal Preparation in Postmenopausal Women.

    PubMed

    Myasoedova, Veronika A; Kirichenko, Tatyana V; Melnichenko, Alexandra A; Orekhova, Varvara A; Ravani, Alessio; Poggio, Paolo; Sobenin, Igor A; Bobryshev, Yuri V; Orekhov, Alexander N

    2016-01-01

    The risk of cardiovascular disease and atherosclerosis progression is significantly increased after menopause, probably due to the decrease of estrogen levels. The use of hormone replacement therapy (HRT) for prevention of cardiovascular disease in older postmenopausal failed to meet expectations. Phytoestrogens may induce some improvements in climacteric symptoms, but their effect on the progression of atherosclerosis remains unclear. The reduction of cholesterol accumulation at the cellular level should lead to inhibition of the atherosclerotic process in the arterial wall. The inhibition of intracellular lipid deposition with isoflavonoids was suggested as the effective way for the prevention of plaque formation in the arterial wall. The aim of this double-blind, placebo-controlled clinical study was to investigate the effect of an isoflavonoid-rich herbal preparation on atherosclerosis progression in postmenopausal women free of overt cardiovascular disease. One hundred fifty-seven healthy postmenopausal women (age 65 ± 6) were randomized to a 500 mg isoflavonoid-rich herbal preparation containing tannins from grape seeds, green tea leaves, hop cone powder, and garlic powder, or placebo. Conventional cardiovascular risk factors and intima-media thickness of common carotid arteries (cIMT) were evaluated at the baseline and after 12 months of treatment. After 12-months follow-up, total cholesterol decreased by 6.3% in isoflavonoid-rich herbal preparation recipients (p = 0.011) and by 5.2% in placebo recipients (p = 0.020); low density lipoprotein (LDL) cholesterol decreased by 7.6% in isoflavonoid-rich herbal preparation recipients (p = 0.040) and by 5.2% in placebo recipients (non-significant, NS); high density lipoprotein (HDL) cholesterol decreased by 3.4% in isoflavonoid-rich herbal preparation recipients (NS) and by 4.5% in placebo recipients (p = 0.038); triglycerides decreased by 6.0% in isoflavonoid-rich herbal preparation recipients (NS) and by 7.1% in

  6. Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis

    PubMed Central

    Li, Li; Chen, Xueping; Liu, Chi C.; Lee, Lai S.; Man, Cornelia; Cheng, Shuk H.

    2016-01-01

    Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae). The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well-studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP) dose-dependently (0–1 μg/ml), demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 μg/ml) induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the anti-estrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 μg/ml) inhibited breast cancer cell growth, with a stronger anti-proliferative effect than resveratrol, a widely studied analog of bakuchiol. High doses of bakuchiol (4, 7, and 10 μg/ml) were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15), Myt1, P-Wee1 (Ser642), p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce apoptosis via intrinsic

  7. Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis.

    PubMed

    Li, Li; Chen, Xueping; Liu, Chi C; Lee, Lai S; Man, Cornelia; Cheng, Shuk H

    2016-01-01

    Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae). The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well-studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP) dose-dependently (0-1 μg/ml), demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 μg/ml) induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the anti-estrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 μg/ml) inhibited breast cancer cell growth, with a stronger anti-proliferative effect than resveratrol, a widely studied analog of bakuchiol. High doses of bakuchiol (4, 7, and 10 μg/ml) were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15), Myt1, P-Wee1 (Ser642), p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce apoptosis via intrinsic

  8. The transillumination technique as a method for the assessment of spermatogenesis using medicinal plants: the effect of extracts of black maca (Lepidium meyenii) and camu camu (Myrciaria dubia) on stages of the spermatogenic cycle in male rats.

    PubMed

    Gonzales, Gustavo F; Vasquez, Vanessa Bertha; Gasco, Manuel

    2013-10-01

    Transillumination technique for assessment of stages of spermatogenic cycle is a useful tool for toxicological studies. This study was designed to determine the effect of two medicinal plants on spermatogenesis in male rats using the transillumination technique. For this, the effect of the combination of a fruit with highest content of ascorbic acid (Myrciaria dubia, camu camu) and extract of black maca (Lepidium meyenii) on seminiferous tubule stages scored by transillumination on intact tubules in adult male rats was assessed. Animals were treated during seven days with vehicle, black maca, camu camu or a mixture of black maca + camu camu and assessed for daily sperm production (DSP), stages of spermatogenic cycle as well as antioxidant activity and levels of flavonoids and polyphenols. Black maca increased stages of spermiation (VII-VIII) and mitosis of germ cells (IX-XI), whereas camu camu increased stages of mitosis (IX-XI) and meiosis (XII). Mixture of maca + camu camu increased stages of spermiation, mitosis and meiosis. All treatments increased DSP (p<0.05) and epididymal sperm count (p<0.05). Total polyphenols, flavonoids levels and antioxidant activity were higher in camu camu (p<0.001) than in black maca. In conclusion, M. dubia (camu camu) has potential effects improving spermatogenesis and co-administered with maca increase stages of mitosis, meiosis and spermiation of the spermatogenic cycle as assessed by the transillumination technique. This technique is becoming increasingly a useful tool for assessment spermatogenesis. PMID:23650963

  9. Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats.

    PubMed

    Hicks, Kimani D; Sullivan, Alana W; Cao, Jinyan; Sluzas, Emily; Rebuli, Meghan; Patisaul, Heather B

    2016-08-01

    Concerns have been raised regarding the potential for endocrine disrupting compounds (EDCs) to alter brain development and behavior. Developmental exposure to bisphenol A (BPA), a ubiquitous EDC, has been linked to altered sociosexual and mood-related behaviors in various animal models and children but effects are inconsistent across laboratories and animal models creating confusion about potential risk in humans. Exposure to endocrine active diets, such as soy, which is rich in phytoestrogens, may contribute to this variability. Here, we tested the individual and combined effects of low dose oral BPA and soy diet or the individual isoflavone genistein (GEN; administered as the aglycone genistin (GIN)) on rat sociosexual behaviors with the hypothesis that soy would obfuscate any BPA-related effects. Social and activity levels were unchanged by developmental exposure to BPA but soy diet had sex specific effects including suppressed novelty preference, and open field exploration in females. The data presented here reinforce that environmental factors, including anthropogenic chemical exposure and hormone active diets, can shape complex behaviors and even reverse expected sex differences.

  10. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats.

    PubMed

    King, Tristan J; Shandala, Tetyana; Lee, Alice M; Foster, Bruce K; Chen, Ke-Ming; Howe, Peter R; Xian, Cory J

    2015-08-06

    Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.

  11. The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters.

    PubMed

    Rigalli, Juan Pablo; Tocchetti, Guillermo Nicolás; Arana, Maite Rocío; Villanueva, Silvina Stella Maris; Catania, Viviana Alicia; Theile, Dirk; Ruiz, María Laura; Weiss, Johanna

    2016-06-28

    Breast cancer is the most frequent malignancy in women. Multidrug resistance due to overexpression of ABC drug transporters is a common cause of chemotherapy failure and disease recurrence. Genistein (GNT) is a phytoestrogen present in soybeans and hormone supplements. We investigated the effect of GNT on the expression and function of ABC transporters in MCF-7 and MDA-MB-231 breast cancer cell lines. Results demonstrated an induction at the protein level of ABCC1 and ABCG2 and of ABCC1 in MCF-7 and MDA-MB-231, respectively. MCF-7 cells showed a concomitant increase in doxorubicin and mitoxantrone efflux and resistance, dependent on ABCG2 activity. ABCC1 induction by GNT in MDA-MB-231 cells modified neither drug efflux nor chemoresistance due to simultaneous acute inhibition of the transporter activity by GNT. All inductions took place at the translational level, as no increment in mRNA was observed and protein increase was prevented by cycloheximide. miR-181a, already demonstrated to inhibit ABCG2 translation, was down-regulated by GNT, explaining translational induction. Effects were independent of classical estrogen receptors. Results suggest potential nutrient-drug interactions that could threaten chemotherapy efficacy, especially in ABCG2-expressing tumors treated with substrates of this transporter. PMID:27033456

  12. Simultaneous determination of phytoestrogens in different medicinal parts of Sophora japonica L. by capillary electrophoresis with electrochemical detection.

    PubMed

    Chu, Qingcui; Fu, Liang; Wu, Ting; Ye, Jiannong

    2005-03-01

    A high-performance capillary electrophoresis with electrochemical detection (CE-ED) method has been developed for the determination of phytoestrogens from the pericarps and seeds of Sophora japonica L. in this work. Genistin, genistein, rutin, kaempferol and quercetin are important bioactive constituents in these plants. The effects of several factors such as the acidity and concentration of running buffer, the separation voltage, the applied potential and the injection time on the CE-ED procedure were investigated. Under the optimum conditions, the five analytes could be well separated within 18 min in a 75 cm length capillary (i.d. 25 microm) at the separation voltage of 16 kV in a 50 mmol L(-1) borax running buffer (pH 9.0). A 300 microm diameter carbon disk electrode was used as the working electrode positioned carefully opposite the outlet of the capillary in a wall-jet configuration at the potential of +950 mV (vs SCE). Detection limits (S/N = 3) ranged from 1.1 x 10(-7) to 2.8 x 10(-7) g mL(-1) for all fi ve analytes. This method was successfully used to analyse dried Flos sophorae immaturus, pericarps and seeds of dried Fructus sophorae after a relatively simple extraction procedure, and the assay results were satisfactory. PMID:15558700

  13. Interaction of bisphenol A (BPA) and soy phytoestrogens on sexually dimorphic sociosexual behaviors in male and female rats.

    PubMed

    Hicks, Kimani D; Sullivan, Alana W; Cao, Jinyan; Sluzas, Emily; Rebuli, Meghan; Patisaul, Heather B

    2016-08-01

    Concerns have been raised regarding the potential for endocrine disrupting compounds (EDCs) to alter brain development and behavior. Developmental exposure to bisphenol A (BPA), a ubiquitous EDC, has been linked to altered sociosexual and mood-related behaviors in various animal models and children but effects are inconsistent across laboratories and animal models creating confusion about potential risk in humans. Exposure to endocrine active diets, such as soy, which is rich in phytoestrogens, may contribute to this variability. Here, we tested the individual and combined effects of low dose oral BPA and soy diet or the individual isoflavone genistein (GEN; administered as the aglycone genistin (GIN)) on rat sociosexual behaviors with the hypothesis that soy would obfuscate any BPA-related effects. Social and activity levels were unchanged by developmental exposure to BPA but soy diet had sex specific effects including suppressed novelty preference, and open field exploration in females. The data presented here reinforce that environmental factors, including anthropogenic chemical exposure and hormone active diets, can shape complex behaviors and even reverse expected sex differences. PMID:27373758

  14. A robust analytical method for measurement of phytoestrogens and related metabolites in serum with liquid chromatography tandem mass spectrometry.

    PubMed

    Jiang, Hongmei; Liao, Xiangjun; Wood, Carla M; Xiao, Chao-Wu; Feng, Yong-Lai

    2016-02-15

    A sensitive and robust method using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for quantitation of 13 phytoestrogens and related metabolites in rat serum samples. A new type of column, the Kinetex core-shell C18 column, was applied for rapid separation of the target analytes in 10min. Two enzymes, sulfatase H-1 and gulcuronidase H-5 from Helix pomatia were compared on the efficiency of releasing the conjugated forms of the target analytes to their free forms in serum samples. The method detection limit (MDL) defined as three times the signal to noise ratio in spiked serum matrix-based solutions was in the range of 0.1-3.5ng/mL. The linear dynamic calibration was in the broad range of 0.2-500ng/mL for all target compounds. Thirty-two rat serum samples from the rats that were fed with diets containing either casein or soy protein isolates with various amounts of isoflavones for 8 weeks were analyzed for the target analytes with the developed method. Nine target analytes were detected in the serum samples. Those detectable compounds are all the metabolites of the dietary isoflavones, suggesting that the diet isoflavones were mostly metabolized to their metabolites in rat.

  15. Ameliorating Effect of Ginseng on Epididymo-Orchitis Inducing Alterations in Sperm Quality and Spermatogenic Cells Apoptosis following Infection by Uropathogenic Escherichia coli in Rats

    PubMed Central

    Eskandari, Mehdi; Jani, Soghra; Kazemi, Mahsa; Zeighami, Habib; Yazdinezhad, Alireza; Mazloomi, Sahar; Shokri, Saeed

    2016-01-01

    Objective Epididymo-orchitis (EO) potentially results in reduced fertility in up to 60% of affected patients. The anti-inflammatory effects of Korean red ginseng (KRG) and its ability to act as an immunoenhancer in parallel with the beneficial effects of this ancient herbal medicine on the reproductive systems of animals and humans led us to evaluate its protective effects against acute EO. Materials and Methods This animal experimental study was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran during 2013-2015. We divided 50 Wistar rats into five following groups (n=10 per group): i. Control-intact animals, ii. Vehicle-phosphate buffered saline (PBS) injection into the vas deferens, iii. KRG-an intraperitoneal (IP) injection of KRG, iv. EO-an injection of uropathogenic Escherichia coli (UPEC) strain M39 into the vas defer- ens, and v. EO/ KRG-injections of both UPEC strain M39 and KRG. The treatment lasted seven days. We then evaluated sperm parameters, number of germ cell layers, Johnson’s criteria, germ cell apoptosis, body weight and relative sex organs weight. Results Acute EO increased the relative weight of prostate and seminal vesicles (P≤0.05). It also reduced sperm quality such as total motility, sperm concentration (P≤0.01), and the percentage of normal sperm (P≤0.001). Moreover, acute EO decreased Miller’s (P≤0.05) and Johnsen’s scores and increased apoptotic indexes of spermatogenic cells (P≤0.001). KRG treatment decreased prostate weight gain (P≤0.05) and improved the percentage of sperm with normal morphology, total motility (P≤0.01), and progressive motility (P≤0.05). The apoptotic indexes of spermatogenic cells reduced (P≤0.001), whereas both Johnsen’s (P≤0.01) and Miller’s criteria increased in the KRG-treated EO testis (P≤0.05). Conclusion Consequently, KRG ameliorated the devastating effects of EO on the sperm retrieved from either

  16. Ameliorating Effect of Ginseng on Epididymo-Orchitis Inducing Alterations in Sperm Quality and Spermatogenic Cells Apoptosis following Infection by Uropathogenic Escherichia coli in Rats

    PubMed Central

    Eskandari, Mehdi; Jani, Soghra; Kazemi, Mahsa; Zeighami, Habib; Yazdinezhad, Alireza; Mazloomi, Sahar; Shokri, Saeed

    2016-01-01

    Objective Epididymo-orchitis (EO) potentially results in reduced fertility in up to 60% of affected patients. The anti-inflammatory effects of Korean red ginseng (KRG) and its ability to act as an immunoenhancer in parallel with the beneficial effects of this ancient herbal medicine on the reproductive systems of animals and humans led us to evaluate its protective effects against acute EO. Materials and Methods This animal experimental study was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran during 2013-2015. We divided 50 Wistar rats into five following groups (n=10 per group): i. Control-intact animals, ii. Vehicle-phosphate buffered saline (PBS) injection into the vas deferens, iii. KRG-an intraperitoneal (IP) injection of KRG, iv. EO-an injection of uropathogenic Escherichia coli (UPEC) strain M39 into the vas defer- ens, and v. EO/ KRG-injections of both UPEC strain M39 and KRG. The treatment lasted seven days. We then evaluated sperm parameters, number of germ cell layers, Johnson’s criteria, germ cell apoptosis, body weight and relative sex organs weight. Results Acute EO increased the relative weight of prostate and seminal vesicles (P≤0.05). It also reduced sperm quality such as total motility, sperm concentration (P≤0.01), and the percentage of normal sperm (P≤0.001). Moreover, acute EO decreased Miller’s (P≤0.05) and Johnsen’s scores and increased apoptotic indexes of spermatogenic cells (P≤0.001). KRG treatment decreased prostate weight gain (P≤0.05) and improved the percentage of sperm with normal morphology, total motility (P≤0.01), and progressive motility (P≤0.05). The apoptotic indexes of spermatogenic cells reduced (P≤0.001), whereas both Johnsen’s (P≤0.01) and Miller’s criteria increased in the KRG-treated EO testis (P≤0.05). Conclusion Consequently, KRG ameliorated the devastating effects of EO on the sperm retrieved from either

  17. Suppression of dendritic cells' maturation and functions by daidzein, a phytoestrogen

    SciTech Connect

    Yum, Min Kyu; Jung, Mi Young; Cho, Daeho; Kim, Tae Sung

    2011-12-15

    Isoflavones are ubiquitous compounds in foods and in the environment in general. Daidzein and genistein, the best known of isoflavones, are structurally similar to 17{beta}-estradiol and known to exert estrogenic effects. They also evidence a broad variety of biological properties, including antioxidant, anti-carcinogenic, anti-atherogenic and anti-osteoporotic activities. Previously, daidzein was reported to increase the phagocytic activity of peritoneal macrophages and splenocyte proliferation, and to inhibit nitric oxide (NO) production in macrophages. However, its potential impacts on immune response in dendritic cells (DCs), antigen-presenting cells that link innate and adaptive immunity, have yet to be clearly elucidated. In this study, we evaluated the effects of isoflavones on the maturation and activation of DCs. Isoflavones (formononetin, daidzein, equol, biochanin A, genistein) were found to differentially affect the expression of CD86, a costimulatory molecule, on lipopolysaccharide (LPS)-stimulated DCs. In particular, daidzein significantly and dose-dependently inhibited the expression levels of maturation-associated cell surface markers including CD40, costimulatory molecules (CD80, CD86), and major histocompatibility complex class II (I-A{sup b}) molecule on LPS-stimulated DCs. Daidzein also suppressed pro-inflammatory cytokine production such as IL-12p40, IL-6 and TNF-{alpha}, whereas it didn't affect IL-10 and IL-1{beta} expression. Furthermore, daidzein enhanced endocytosis and inhibited the allo-stimulatory ability of LPS-stimulated DCs on T cells, indicating that daidzein treatment can inhibit the functional maturation of DCs. These results demonstrate that daidzein may exhibit immunosuppressive activity by inhibiting the maturation and activation of DCs. -- Highlights: Black-Right-Pointing-Pointer Daidzein inhibited expression of maturation-associated cell surface markers in DCs. Black-Right-Pointing-Pointer Daidzein suppressed expression of

  18. Molecular Cloning of Spergen-4, Encoding a Spermatogenic Cell-Specific Protein Associated with Sperm Flagella and the Acrosome Region in Rat Spermatozoa.

    PubMed

    Howida, Ali; Salaheldeen, Elsaid; Iida, Hiroshi

    2016-04-01

    We used a differential display in combination with complementary DNA (cDNA) cloning approach to isolate a novel rat gene LOC690919 with an open reading frame of 1227-length nucleotides encoding a protein of 409 amino acids. This gene was designated as Spergen-4 (a spermatogenic cell-specific gene-4). Spergen-4 mRNA was highly expressed in testis, and its expression was detected in rat testis starting at three weeks of postnatal development and persisting up to adulthood. Mouse and human orthologs, which lack N-terminal 77 amino acid residues of rat Spegen-4, were found in the database. Immunofluorescence microscopy and immunoblot analysis demonstrated that Spergen-4 was not expressed in spermatogonia, spermatocytes, and round spermatids, but was restrictedly detected at sperm head, cytoplasm, and developing flagella of elongated spermatids in rat testis. In mature spermatozoa, Spergen-4 was detected at the acrosome region as well as the principal piece of flagella. Spergen-4 immunosignal disappeared from sperm heads on acrosome reaction induced by progesterone. These data suggest that Spergen-4 integrated into elongated spermatids during spermiogenesis serves as a constituent for acrosome region and flagella of rat spermatozoa. PMID:27032685

  19. Developmental Phases of the Seminal Vesicle related to the Spermatogenic Stages in the Testicular Lobules of Neptunea (Barbitonia) cumingii (Gastropoda: Buccinidae)

    PubMed Central

    Kim, Sung Han

    2016-01-01

    Cytological changes of the epithelial cells according to the developmenatal phases of the seminal vesicle related to the spermatogenic stages in the testicular lobules during spermagenesis in male Neptunea (Barbitonia) cumingii (Gastropoda: Buccinidae) were investigated monthly by electron microscopical and histological observations. N. (B) cumingii is dioecious, and an internal fertilization species. The male genital organ is located near the tentacles. The spermatozoon is approximatley 50 μm in length. The axoneme of the tail flagellum consists of nine pairs of microtubles at the periphery and one pair at the center. The process of germ cell development during spermatogenesis can be divided into five succesive stages: (1) spermatogonia, (2) primary spermatocytes, (3) secondary spermatocytes, (4) spermatids, and (5) spermatozoa. A considerable amount of spermatozoa make their appearance in the testicular lobules (or acini) and some of them are tranported from the testis towards the seminal vesicles until late July. In this study, the developmental phases of the epithelial cells of the seminal vesicles of N. (B.) cumingii could be classified into four phases: (1) S-I phase (resting), (2) S-Ⅱphase (early accumulating), (3) S-Ⅲ phase (accumulating), and (4) S-IV phase (spent). However, in case of N. (B.) arthritica cumingii, the developmental phases of the seminal vesicle were devided into three phases: (1) resting, (2) accumulating and (3) spent. Granular bodies in the inner layer of the seminal vesicles are involved in resorption of digestion of residual spermatozoa. PMID:27796006

  20. HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

    PubMed Central

    Lim, Shu Ly; Geoghegan, Joel; Hempfling, Anna-Lena; Bergmann, Martin; Goodnow, Christopher C.; Ormandy, Christopher J.; Wong, Lee; Mann, Jeff; Scott, Hamish S.; Jamsai, Duangporn; Adelson, David L.

    2015-01-01

    piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2’ O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program. PMID:26496356

  1. HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse.

    PubMed

    Lim, Shu Ly; Qu, Zhi Peng; Kortschak, R Daniel; Lawrence, David M; Geoghegan, Joel; Hempfling, Anna-Lena; Bergmann, Martin; Goodnow, Christopher C; Ormandy, Christopher J; Wong, Lee; Mann, Jeff; Scott, Hamish S; Jamsai, Duangporn; Adelson, David L; O'Bryan, Moira K

    2015-10-01

    piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2' O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program. PMID:26496356

  2. Molecular Cloning of Spergen-4, Encoding a Spermatogenic Cell-Specific Protein Associated with Sperm Flagella and the Acrosome Region in Rat Spermatozoa.

    PubMed

    Howida, Ali; Salaheldeen, Elsaid; Iida, Hiroshi

    2016-04-01

    We used a differential display in combination with complementary DNA (cDNA) cloning approach to isolate a novel rat gene LOC690919 with an open reading frame of 1227-length nucleotides encoding a protein of 409 amino acids. This gene was designated as Spergen-4 (a spermatogenic cell-specific gene-4). Spergen-4 mRNA was highly expressed in testis, and its expression was detected in rat testis starting at three weeks of postnatal development and persisting up to adulthood. Mouse and human orthologs, which lack N-terminal 77 amino acid residues of rat Spegen-4, were found in the database. Immunofluorescence microscopy and immunoblot analysis demonstrated that Spergen-4 was not expressed in spermatogonia, spermatocytes, and round spermatids, but was restrictedly detected at sperm head, cytoplasm, and developing flagella of elongated spermatids in rat testis. In mature spermatozoa, Spergen-4 was detected at the acrosome region as well as the principal piece of flagella. Spergen-4 immunosignal disappeared from sperm heads on acrosome reaction induced by progesterone. These data suggest that Spergen-4 integrated into elongated spermatids during spermiogenesis serves as a constituent for acrosome region and flagella of rat spermatozoa.

  3. Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death.

    PubMed

    Mishra, Durga Prasad; Pal, Rajarshi; Shaha, Chandrima

    2006-01-27

    Bcl-x exists in two isoforms, the anti-apoptotic form Bcl-xL and the proapoptotic form Bcl-xS. The critical balance between the two forms appears to be important for cell survival; however, it is still not clear exactly how the vital balance is maintained. Using an in vitro spermatogenic cell apoptosis model, this study provides a new insight into the possible role of Ca2+ in regulating the Bcl-xS and Bcl-xL expression. 2,5-Hexanedione, a metabolite of the common industrial solvent n-hexane, caused a significant increase in reactive oxygen species followed by an enhancement of intracellular Ca2+ through the T-type Ca2+ channels. Consequent to the above changes, expression of Bcl-xS increased with a concomitant drop in Bcl-xL expression, thus altering the ratio of the two proteins. Impediment of Ca2+ influx by using a T-type Ca2+ channel blocker pimozide resulted in a decrease in Bcl-xS and an increase in Bcl-xL expression. This caused prevention of mitochondrial potential loss, reduction of caspase-3 activity, inhibition of DNA fragmentation, and increase in cell survival. Alternatively, Ca2+ ionophores caused an increase of Bcl-xS encoding isoform over the Bcl-xL-encoding isoform. Therefore, this study proposes a role for Ca2+ in regulation of Bcl-xS and Bcl-xL expression and ultimately cell fate.

  4. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model.

    PubMed

    van Duursen, Majorie B M; Smeets, Evelien E J W; Rijk, Jeroen C W; Nijmeijer, Sandra M; van den Berg, Martin

    2013-06-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided. PMID:23541764

  5. Up-regulation of interleukin-4 production via NF-AT/AP-1 activation in T cells by biochanin A, a phytoestrogen and its metabolites

    SciTech Connect

    Park, Jin; Chung, Su Wol; Kim, Seung Hyun; Kim, Tae Sung . E-mail: tskim@korea.ac.kr

    2006-05-01

    Phytoestrogens are naturally occurring compounds derived from plants. Although phytoestrogens exhibit many biological functions including estrogen agonist/antagonist properties, the effect on allergic responses remains unclear. In this study, we investigated whether biochanin A, a phytoestrogen and its metabolites, genistein, p-ethylphenol and phenolic acid, affect production of IL-4, a pro-inflammatory cytokine closely associated with allergic immune responses, in primary CD4{sup +} T cells and EL4 T lymphoma cells. Biochanin A, genistein and p-ethylphenol significantly enhanced IL-4 production from both CD4{sup +} T cells and EL4 cells in a dose-dependent manner, while phenolic acid did not. Biochanin A, genistein and p-ethylphenol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of a P4 site carrying NF-AT and AP-1 binding sites. In addition, biochanin A, genistein and p-ethylphenol increased both NF-AT and AP-1 DNA binding activities, indicating that they might enhance IL-4 production via NF-AT/AP-1 activation. Furthermore, biochanin A, genistein and p-ethylphenol increased p38 MAPK phosphorylation and PKC activity, while they did not affect ERK phosphorylation. The enhanced NF-AT DNA binding activities were suppressed by inhibitors for PI3-K and PKC, but not by p38 MAPK inhibitors. In contrast, the enhanced AP-1 DNA binding activities and p38 MAPK phosphorylation were significantly suppressed by specific inhibitors for PKC and p38 MAPK, but not by PI3-K inhibitors. These results demonstrate, for the first time, that biochanin A, genistein and p-ethylphenol enhance IL-4 production in activated T cells by two independent pathways, PI3-K/PKC/NF-AT and PKC/p38 MAPK/AP-1.

  6. Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model.

    PubMed

    van Duursen, Majorie B M; Smeets, Evelien E J W; Rijk, Jeroen C W; Nijmeijer, Sandra M; van den Berg, Martin

    2013-06-01

    Breast cancer treatment by the aromatase inhibitor Letrozole (LET) or Selective Estrogen Receptor Modulator Tamoxifen (TAM) can result in the onset of menopausal symptoms. Women often try to relieve these symptoms by taking menopausal supplements containing high levels of phytoestrogens. However, little is known about the potential interaction between these supplements and breast cancer treatment, especially aromatase inhibitors. In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which could not be prevented by physiologically relevant LET and 4OH-TAM concentrations. Differences in relative effect potencies between the H295R/MCF-7 co-culture model and ER-activation in BG1Luc4E2 cells, were due to the effects of the phytoestrogens on steroidogenesis. All tested supplements and GEN induced aromatase activity, while 8PN was a strong aromatase inhibitor. Steroidogenic profiles upon GEN and 8PN exposure indicated a strong inhibitory effect on steroidogenesis in H295R cells and H295R/MCF-7 co-cultures. Based on our in vitro data we suggest that menopausal supplement intake during breast cancer treatment should better be avoided, at least until more certainty regarding the safety of supplemental use in breast cancer patients can be provided.

  7. Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1

    SciTech Connect

    Hwang, Yong Pil; Jeong, Hye Gwang

    2008-12-15

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. The phytoestrogen puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicines for thousands of years. Recent studies have indicated that the estrogen receptor (ER), through interaction with p85, regulates phosphoinositide 3-kinase (PI3K) activity, revealing a physiologic, non-nuclear function of ER that may be relevant in cytoprotection. In this study, we demonstrate that the phytoestrogen puerarin inhibits tert-butyl hydroperoxide (t-BHP)-induced oxidative injury via an ER-dependent G{beta}1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of Hepa1c1c7 and HepG2 cells with puerarin significantly reduced t-BHP-induced caspase-3 activation and subsequent cell death. Also, puerarin up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-BHP. Moreover, puerarin induced Nrf2 nuclear translocation, which is upstream of puerarin-induced HO-1 expression, and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Puerarin-induced up-regulation of HO-1 and cytoprotection against t-BHP were abolished by silencing Nrf2 expression with specific siRNA. Also, puerarin-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that puerarin augments cellular antioxidant defense capacity through ER-dependent HO-1 induction via the G{beta}1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress.

  8. Suppressive effect of neonatal treatment with a phytoestrogen, coumestrol, on lordosis and estrous cycle in female rats.

    PubMed

    Kouki, Tom; Okamoto, Miho; Wada, Shizuko; Kishitake, Miki; Yamanouchi, Korehito

    2005-01-15

    The neural control systems for the ovulatory cycle and lordosis behavior are sexually differentiated by estrogen during the perinatal period in rats. In the present study, the effects of a single neonatal injection with the phytoestrogen, coumestrol, on female reproductive functions were investigated. Female rats were injected subcutaneously with 1 or 3mg coumestrol (CM1, CM3), 1mg genistein (GS1), 1mg estradiol (E2), or oil at day 5 after birth (birth day=day 1) and an estrous cycle check and lordosis behavior test were performed. As a result, vaginal opening was advanced in CM1-, CM3- or E2-treated females. A vaginal smear check indicated that oil- or GS1-treated females showed a constant 4- or 5-day estrous cycle, whereas CM1-, CM3- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovary weights in the CM1-, CM3- or E2-treated groups were lower than those in the oil- and GS1-treated groups and no corpora lutea were found in any rats of these three groups, except for two E2-treated rats. Behavioral tests were carried out after implantation of E2-tubes. All rats in the CM1-, GS1-treated groups showed a high lordosis quotient (LQ), being comparable to that in the oil-treated females. On the other hand, LQs in the CM3, E2 or male groups were lower than that in the control female group. These results suggest that a single neonatal injection of 3 mg coumestrol was effective in suppressing the functions of ovulation-inducing mechanisms and the induction of lordosis, but 1mg coumestrol was effective in only the estrous cycle of female rats.

  9. A diet containing the soy phytoestrogen genistein causes infertility in female rats partially deficient in UDP glucuronyltransferase

    SciTech Connect

    Seppen, Jurgen

    2012-11-01

    Soy beans contain genistein, a natural compound that has estrogenic effects because it binds the estrogen receptor with relatively high affinity. Genistein is therefore the most important environmental estrogen in the human diet. Detoxification of genistein is mediated through conjugation by UDP-glucuronyltransferase 1 and 2 (UGT1 and UGT2) isoenzymes. Gunn rats have a genetic deficiency in UGT1 activity, UGT2 activities are not affected. Because our Gunn rats stopped breeding after the animal chow was changed to a type with much higher soy content, we examined the mechanism behind this soy diet induced infertility. Gunn and control rats were fed diets with and without genistein. In these rats, plasma levels of genistein and metabolites, fertility and reproductive parameters were determined. Enzyme assays showed reduced genistein UGT activity in Gunn rats, as compared to wild type rats. Female Gunn rats were completely infertile on a genistein diet, wild type rats were fertile. Genistein diet caused a persistent estrus, lowered serum progesterone and inhibited development of corpora lutea in Gunn rats. Concentrations of total genistein in Gunn and control rat plasma were identical and within the range observed in humans after soy consumption. However, Gunn rat plasma contained 25% unconjugated genistein, compared to 3.6% in control rats. This study shows that, under conditions of reduced glucuronidation, dietary genistein exhibits a strongly increased estrogenic effect. Because polymorphisms that reduce UGT1 expression are prevalent in the human population, these results suggest a cautionary attitude towards the consumption of large amounts of soy or soy supplements. -- Highlights: ► Gunn rats are partially deficient in detoxification by UDP glucuronyltransferases. ► Female Gunn rats are infertile on a soy containing diet. ► Soy contains genistein, a potent phytoestrogen. ► Inefficient glucuronidation of genistein causes female infertility.

  10. Systemic administration of diarylpropionitrile (DPN) or phytoestrogens does not affect anxiety-related behaviors in gonadally intact male rats

    PubMed Central

    Patisaul, Heather B.; Burke, Katherine T.; Hinkle, Ruth E.; Adewale, Heather L.; Shea, Damian

    2009-01-01

    The development of highly selective agonists for the two major subforms of the estrogen receptor (ERa and ERϐ) has produced new experimental methodologies for delineating the distinct functional role each plays in neurobehavioral biology. It has also been suggested that these compounds might have the potential to treat estrogen influenced behavioral disorders, such as anxiety and depression. Prior work has established that the ERϐ agonist, diarylpropionitrile (DPN) is anxiolytic in gonadectomized animals of both sexes, but whether or not this effect persists in gonadally intact individuals is unknown. Isoflavone phytoestrogens, also potent but less selective ERϐ agonists, have also been shown to influence anxiety in multiple species and are becoming more readily available to humans as health supplements. Here we determined the effects of 0.5, 1 or 2 mg/kg DPN, 1 mg/kg of the ERa agonist propyl-pyrazole-triol (PPT), 3 or 20 mg/kg of the isoflavone equol (EQ) and 3 or 20 mg/kg of the isoflavone polyphenol resveratrol (RES) on anxiety behavior in the gonadally intact male rat using the light/dark box and the elevated plus maze. We first determined that DPN can be successfully administered either orally or by subcutaneous injection, although plasma DPN levels are significantly lower if given orally. Once injected, plasma levels peak rapidly and then decline to baseline levels within 3 hours of administration. For the behavioral studies, all compounds were injected and the animals were tested within 3 hours of treatment. None of the compounds, at any of the doses, significantly altered anxiety-related behavior. Plasma testosterone levels were also not significantly altered suggesting that these compounds do not interfere with endogenous androgen levels. The results suggest that the efficacy of ERϐ agonists may depend on gonadal status. Therefore the therapeutic potential of ERϐ selective agonists to treat mood disorders may be limited. PMID:19071129

  11. Nuclear receptors: potential biomarkers for assessing physiological functions of soy proteins and phytoestrogens.

    PubMed

    Xiao, Chao Wu; Wood, Carla; Gilani, G Sarwar

    2006-01-01

    Soy consumption is associated with decreased incidence of chronic diseases, including cardiovascular diseases, atherosclerosis, diabetes, osteoporosis, and certain types of cancers. However, consumption of high amounts of soy isoflavones may adversely influence endocrine functions, such as thyroid function and reproductive performance, because of their structural similarity to endogenous estrogens. Nuclear receptors are a group of transcription factors that play critical roles in the regulation of gene expression and physiological functions through direct interaction with target genes. Modulation of the abundance of these receptors, such as changing their gene expression, alters the sensitivity of the target cells or tissues to the stimulation of ligands, and eventually affects the relevant physiological functions, such as growth, development, osteogenesis, immune response, lipogenesis, reproductive process, and anticarcinogenesis. A number of studies have shown that the bioactive components in soy can modify the expression of these receptors in various tissues and cancer cells, which is believed to be a key intracellular mechanism by which soy components affect physiological functions. This review summarizes the current understanding of the modulation of nuclear receptors by soy proteins and isoflavones, and focuses especially on the receptors for estrogens, progesterone, androgen, vitamin D, retinoic acid, and thyroid hormones as well as the potential impact on physiological functions.

  12. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

    PubMed Central

    Zin, Siti Rosmani Md; Omar, Siti Zawiah; Khan, Norhayati Liaqat Ali; Musameh, Nurul Iftitah; Das, Srijit; Kassim, Normadiah M

    2013-01-01

    OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-α in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors. PMID:23525324

  13. Immunohistological profile of the Ras homologous B protein (RhoB) in human testes showing normal spermatogenesis, spermatogenic arrest and Sertoli cell only syndrome.

    PubMed

    Adly, Mohamed A; Hussein, Mahmoud Rezk Abdelwahed

    2010-09-01

    Ras homologous B protein (RhoB) belongs to the Ras homologous subfamily which consists of low molecular weight (21 kDa) GTP-binding proteins. Rho proteins are regulatory molecules associated with various kinases and as such they mediate changes in cell shape, contractility, motility and gene expression. To date, no data are available about the expression pattern of RhoB protein in the human testis showing normal and abnormal spermatogenesis. The present study addresses these issues. Human testicular biopsy specimens were obtained from patients suffering from post-testicular infertility (testis showing normal spermatogenesis, 10 cases) and testicular infertility (testis showing Sertoli cell only syndrome and spermatogenic arrest, 10 patients each). The expression of RhoB was examined using in situ immunofluorescent staining methods. In testes showing normal spermatogenesis, RhoB had a strong expression in the seminiferous epithelium (cytoplasm of Sertoli-cells, spermatogonia and spermatocytes) and in the interstitium (Leydig cells). RhoB expression was weak in the myofibroblasts and absent in the spermatids and sperms. In the testes showing abnormal spermatogenesis, RhoB expression was moderate in the seminiferous epithelium (cytoplasm of Sertoli cells, spermatogonia and spermatocytes) and was completely absent in the Leydig cells, myofibroblasts, spermatids and sperms. To the best of our knowledge, this study provides the first morphological indication that RhoB protein is expressed in human testis and its expression undergoes testicular infertility associated changes. These findings suggest the involvement of RhoB in the process of spermatogenesis in human and their possible therapeutic ramifications in testicular infertility are open for further investigations.

  14. Disruption of a Spermatogenic Cell-Specific Mouse Enolase 4 (Eno4) Gene Causes Sperm Structural Defects and Male Infertility1

    PubMed Central

    Nakamura, Noriko; Dai, Qunsheng; Williams, Jason; Goulding, Eugenia H.; Willis, William D.; Brown, Paula R.; Eddy, Edward M.

    2013-01-01

    ABSTRACT Sperm utilize glycolysis to generate ATP required for motility, and several spermatogenic cell-specific glycolytic isozymes are associated with the fibrous sheath (FS) in the principal piece of the sperm flagellum. We used proteomics and molecular biology approaches to confirm earlier reports that a novel enolase is present in mouse sperm. We then found that a pan-enolase antibody, but not antibodies to ENO2 and ENO3, recognized a protein in the principal piece of the mouse sperm flagellum. Database analyses identified two previously uncharacterized enolase family-like candidate genes, 64306537H0Rik and Gm5506. Northern analysis indicated that 64306537H0Rik (renamed Eno4) was transcribed in testes of mice by Postnatal Day 12. To determine the role of ENO4, we generated mice using embryonic stem cells in which an Eno4 allele was disrupted by a gene trap containing a beta galactosidase (beta-gal) reporter (Eno4+/Gt). Expression of beta-gal occurred in the testis, and male mice homozygous for the gene trap allele (Eno4Gt/Gt) were infertile. Epididymal sperm numbers were 2-fold lower and sperm motility was reduced substantially in Eno4Gt/Gt mice compared to wild-type mice. Sperm from Eno4Gt/Gt mice had a coiled flagellum and a disorganized FS. The Gm5506 gene encodes a protein identical to ENO1 and also is transcribed at a low level in testis. We conclude that ENO4 is required for normal assembly of the FS and provides most of the enolase activity in sperm and that Eno1 and/or Gm5506 may encode a minor portion of the enolase activity in sperm. PMID:23446454

  15. Effect of the supplementation of dietary rich phytoestrogens in altering the vitamin D levels in diet induced osteoporotic rat model.

    PubMed

    Chennaiah, S; Vijayalakshmi, V; Suresh, C

    2010-07-01

    Plant-derived estrogen-like compounds such as isoflavones (IF) especially daidzein and genistein are said to be preserving the bone in the osteoporotic conditions. However, it is not known whether a combination of IF and calcium (Ca) supplementation attenuates losses in bone mass and prevents the loss of vitamin D (VD). The present study addresses the role of phytoestrogens (PE) and Ca supplementation in low Ca and low VD diet induced osteoporosis (OSP). Cowpea (CP) which has high amount of the IF was selected to study its effect on diet induced osteoporotic conditions. Female weanling WNIN rats (total of 68) were divided into five groups and fed for five weeks on semisynthetic diet with low Ca (0.15%) and low VD (0.1IU/day/rat) in combination with low (10 mg/kg) or high (25 mg/kg) concentrations of PEs derived from CPIF. The study groups are: (I) normal Ca(0.47%) and normal VD (25IU/day/rat), (II) low Ca+low VD, (III) low Ca+low VD+low CPIF (10 mg/kg diet), (IV) low Ca+low VD+high CPIF (25 mg/kg diet) and (V) low Ca+low VD+17-(-estradiol (3.2 mg/kg diet). After the development of OSP the group II was subgrouped into: (SG I) continued on low Ca+VD, (SG II) low CPIF, (SG III) high CPIF, (SG IV) 17-beta-estradiol and (SG V) normal Ca and VD. Serum 25-VD levels were in the range of 14-38 ng/ml in groups I, III, IV and V, where as the values were very low in the group II (5.8 ng/ml). These were partially reversed upon supplementation of CPIF. The results correlated with altered Ca levels, body weight, bone mineral density and content and other related biochemical parameters. The paper further explains the possibility of protective and therapeutic role of VD in the presence of CPIF in osteoporotic health manifestations. PMID:20362669

  16. Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary-gonadal axis and Leydig cell steroidogenesis.

    PubMed

    Svechnikov, K; Supornsilchai, V; Strand, M-L; Wahlgren, A; Seidlova-Wuttke, D; Wuttke, W; Söder, O

    2005-10-01

    Procymidone is a fungicide with anti-androgenic properties, widely used to protect fruits from fungal infection. Thereby it contaminates fruit products prepared for human consumption. Genistein-containing soy products are increasingly used as food additives with health-promoting properties. Therefore we examined the effects of long-term dietary administration (3 months) of the anti-androgen procymidone (26.4 mg/animal per day) or the phytoestrogen genistein (21.1 mg/animal per day) to rats on the pituitary-gonadal axis in vivo, as well as on Leydig cell steroidogenesis and on spermatogenesis ex vivo. The procymidone-containing diet elevated serum levels of LH and testosterone and, furthermore, Leydig cells isolated from procymidone-treated animals displayed an enhanced capacity for producing testosterone in response to stimulation by hCG or dibutyryl cAMP, as well as elevated expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450 scc) and cytochrome P450 17alpha (P450c17). In contrast, the rate of DNA synthesis during stages VIII and IX of spermatogenesis in segments of seminiferous tubules isolated from genistein-treated rats was decreased without accompanying changes in the serum level of either LH or testosterone. Nonetheless, genistein did suppress the ex vivo steroidogenic response of Leydig cells to hCG or dibutyryl cAMP by down-regulating their expression of P450 scc. Considered together, our present findings demonstrate that long-term dietary administration of procymidone or genistein to rats exerts different effects on the pituitary-gonadal axis in vivo and on Leydig cell steroidogenesis ex vivo. Possibly as a result of disruption of hormonal feedback control due to its anti-androgenic action, procymidone activates this endocrine axis, thereby causing hyper-gonadotropic activation of testicular steroidogenesis. In contrast, genistein influences spermatogenesis and significantly inhibits Leydig cell

  17. Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen receptors alpha and beta.

    PubMed

    Roelens, Frederik; Heldring, Nina; Dhooge, Willem; Bengtsson, Martin; Comhaire, Frank; Gustafsson, Jan-Ake; Treuter, Eckardt; De Keukeleire, Denis

    2006-12-14

    In search of therapeutic agents for estrogen-related pathologies, phytoestrogens are being extensively explored. In contrast to naringenin, 8-prenylnaringenin is a potent hop-derived estrogenic compound, highlighting the importance of the prenyl group for hormonal activity. We investigated the effects of substituting the prenyl group at C(8) with alkyl chains of varying lengths and branching patterns on estrogen receptor (ER) subtype ERalpha- and ERbeta-binding affinities and transcriptional activities. In addition, features of the ligand-induced receptor conformations were explored using a set of specific ER-binding peptides. The new 8-alkylnaringenins were found to span an activity spectrum ranging from full agonism to partial agonism to antagonism. Most strikingly, 8-(2,2-dimethylpropyl)naringenin exhibited full agonist character on ERalpha, but pronounced antagonist character on ERbeta. Knowledge on how ER-subtype-selective activities can be designed provides valuable information for future drug or tool compound discovery.

  18. The phytoestrogenic Cyclopia extract, SM6Met, increases median tumor free survival and reduces tumor mass and volume in chemically induced rat mammary gland carcinogenesis.

    PubMed

    Visser, Koch; Zierau, Oliver; Macejová, Dana; Goerl, Florian; Muders, Michael; Baretton, Gustavo B; Vollmer, Günter; Louw, Ann

    2016-10-01

    SM6Met, a phytoestrogenic extract of Cyclopia subternata indigenous to the Western Cape province of South Africa, displays estrogenic attributes with potential for breast cancer chemoprevention. In this study, we report that SM6Met, in the presence of estradiol, induces a significant cell cycle G0/G1 phase arrest similar to the selective estrogen receptor modulator, tamoxifen. Furthermore, as a proof of concept, in the N-Methyl-N-nitrosourea induced rat mammary gland carcinogenesis model, SM6Met increases tumor latency by 7days and median tumor free survival by 42 days, while decreasing palpable tumor frequency by 32%, tumor mass by 40%, and tumor volume by 53%. Therefore, the current study provides proof of concept that SM6Met has definite potential as a chemopreventative agent against the development and progression of breast cancer. PMID:27142456

  19. Sociodemographic and lifestyle variables are compound- and class-specific correlates of urine phytoestrogen concentrations in the U.S. population.

    PubMed

    Rybak, Michael E; Sternberg, Maya R; Pfeiffer, Christine M

    2013-06-01

    Isoflavones and lignans are plant-derived dietary compounds generally believed to be beneficial to human health. We investigated the extent to which sociodemographic (age, sex, race-ethnicity, education, and income) and lifestyle variables (smoking, alcohol consumption, BMI, physical activity, and dietary supplement use) were correlates of spot urine concentration for daidzein, genistein, O-desmethylangolensin (DMA), equol, enterodiol, and enterolactone in the U.S. population aged ≥ 20 y (NHANES 2003-2006). We performed correlation analyses with continuous variables and calculated stratified unadjusted geometric means for each sociodemographic and lifestyle variable. We used bivariate significance testing and covariate adjustment by use of multiple regression models to identify influential variables and used β coefficients to estimate relative effects. Urine creatinine was also included in our analyses because of its use in correcting for variable dilution in spot urine samples. We observed many significant (P < 0.05) associations with the sociodemographic and lifestyle variables that withstood covariate adjustment. Smoking was a significant correlate of urine DMA and enterolactone, with concentrations at least 25% lower in smokers vs. nonsmokers. Consumers of 1 daily alcoholic drink vs. none were estimated to have 18-21% lower urine equol and DMA concentrations. A 25% increase in BMI was associated with a 21% lower urine enterolactone concentration, and increasing physical activity was associated with a >6% higher urine enterolactone concentration. Dietary supplement use was not significantly associated with any of the urine phytoestrogens. Overall, we found that relationships between sociodemographic and lifestyle variables and urine phytoestrogen concentration were highly compound and class specific.

  20. Molecular analysis of the genus Asparagus based on matK sequences and its application to identify A. racemosus, a medicinally phytoestrogenic species.

    PubMed

    Boonsom, Teerawat; Waranuch, Neti; Ingkaninan, Kornkanok; Denduangboripant, Jessada; Sukrong, Suchada

    2012-07-01

    The plant Asparagus racemosus is one of the most widely used sources of phytoestrogens because of its high content of the steroidal saponins, shatavarins I-IV, in roots. The dry root of A. racemosus, known as "Rak-Sam-Sip" in Thai, is one of the most popular herbal medicines, used as an anti-inflammatory, an aphrodisiac and a galactagogue. Recently, the interest in plant-derived estrogens has increased tremendously, making A. racemosus particularly important and a possible target for fraudulent labeling. However, the identification of A. racemosus is generally difficult due to its similar morphology to other Asparagus spp. Thus, accurate authentication of A. racemosus is essential. In this study, 1557-bp nucleotide sequences of the maturase K (matK) gene of eight Asparagus taxa were analyzed. A phylogenetic relationship based on the matK gene was also constructed. Ten polymorphic sites of nucleotide substitutions were found within the matK sequences. A. racemosus showed different nucleotide substitutions to the other species. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the matK gene was developed to discriminate A. racemosus from others. Only the 650-bp PCR product from A. racemosus could be digested with BssKI into two fragments of 397 and 253-bp while the products of other species remained undigested. Ten commercially crude drugs were analyzed and revealed that eight samples were derived from A. racemosus while two samples of that were not. Thus, the PCR-RFLP analysis of matK gene was shown to be an effective method for authentication of the medicinally phytoestrogenic species, A. racemosus.

  1. Dietary genistein stimulates mammary development in gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The possible role of the phytoestrogen, genistein, on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplem...

  2. Combined effects of dietary phytoestrogen and synthetic endocrine-active compound on reproductive development in Sprague-Dawley rats: genistein and methoxychlor.

    PubMed

    You, Li; Casanova, Mercedes; Bartolucci, Erika J; Fryczynski, Mary W; Dorman, David C; Everitt, Jeffrey I; Gaido, Kevin W; Ross, Susan M; Heck Hd, Henry d'A

    2002-03-01

    Humans and wildlife are frequently exposed to mixtures of endocrine active-compounds (EAC). The objective of the present study was to investigate the potential of the phytoestrogen genistein to influence the reproductive developmental toxicity of the endocrine-active pesticide methoxychlor. Three levels of genistein (0, 300, or 800 ppm) and two levels of methoxychlor (0 or 800 ppm) were used in this study. Sprague-Dawley rats were exposed to the two compounds, either alone or in combinations, through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning. Both compounds, methoxychlor in particular, were associated with reduced body growth at 800 ppm, but pregnancy outcome was not affected by either treatment. An acceleration of vaginal opening (VO) in the exposed female offspring was the only observed effect of genistein at 300 ppm. Exposure to 800 ppm genistein or 800 ppm methoxychlor caused accelerated VO and also altered estrous cyclicity toward persistent estrus in the female offspring. The estrogenic responses to genistein and methoxychlor administered together were apparently accumulative of the effects associated with each compound alone. Methoxychlor, but not genistein, delayed preputial separation (PPS) in the male rats. When administered with methoxychlor, genistein at 800 ppm enhanced the effect of methoxychlor on delaying PPS. Genistein and methoxychlor treatment did not change gender-specific motor activity patterns in either sex. To explore possible mechanisms for interaction between the two compounds on development, we performed estrogen receptor (ER)- and androgen receptor (AR)-based in vitro transcriptional activation assays using genistein and the primary methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). While the in vitro assays supported the estrogenic effects of genistein and methoxychlor and the antiandrogenic effects of methoxychlor, the reactivity of these

  3. Impact of neonatal exposure to the ERα agonist PPT, bisphenol-a or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats

    PubMed Central

    Patisaul, Heather B.; Todd, Karina L.; Mickens, Jillian A.; Adewale, Heather B.

    2013-01-01

    Neonatal exposure to endocrine disrupting compounds (EDCs) can impair reproductive physiology, but the specific mechanisms by which this occurs remain largely unknown. Growing evidence suggests that kisspeptin (KISS) neurons play a significant role in the regulation of pubertal onset and ovulation, therefore disruption of KISS signaling could be a mechanism by which EDCs impair reproductive maturation and function. We have previously demonstrated that neonatal exposure to phytoestrogens decreases KISS fiber density in the anterior hypothalamus of female rats, an effect which was associated with early persistent estrus and the impaired activation gonadotropin releasing hormone (GnRH) neurons. The goals of the present study were to (1) determine if an ERα selective agonist (PPT) or bisphenol-A (BPA) could produce similar effects on hypothalamic KISS content in female rats and (2) to determine if male KISS fiber density was also vulnerable to disruption by EDCs. We first examined the effects of neonatal exposure to PPT, a low (50 μg/kg bw) BPA dose, and a high (50 mg/kg bw) BPA dose on KISS immunoreactivity (-ir) in the anterior ventral periventricular (AVPV) and arcuate (ARC) nuclei of adult female rats, using estradiol benzoate (EB) and a sesame oil vehicle as controls. AVPV KISS-ir, following ovariectomy (OVX) and hormone priming, was significantly lower in the EB and PPT groups but not the BPA groups. ARC KISS-ir levels were significantly diminished in the EB and high dose BPA groups, and there was a nonsignificant trend for lower KISS-ir in the PPT group. We next examined effects of neonatal exposure to a low (50μg/kg bw) dose of BPA and the phytoestrogens genistein (GEN) and equol (EQ) on KISS-ir in the AVPV and ARC of adult male rats, using OVX females as an additional control group. None of the compounds affected KISS-ir in the male hypothalamus. Our results suggest that the organization of hypothalamic KISS fibers may be vulnerable to disruption by EDC

  4. The effect of zinc and phytoestrogen supplementation on the changes in mineral content of the femur of rats with chemically induced mammary carcinogenesis.

    PubMed

    Skrajnowska, Dorota; Korczak, Barbara Bobrowska-; Tokarz, Andrzej; Kazimierczuk, Agata; Klepacz, Marta; Makowska, Justyna; Gadzinski, Blazej

    2015-10-01

    The aim of this study was to assess skeletal effects of zinc or zinc with phytoestrogen (resveratrol or genistein) supplementation in an animal model of rats with DMBA-induced mammary carcinogenesis. The changes in bone parameters such as the length and mass were examined, as well as the changes in concentrations of selected minerals: calcium, magnesium, zinc, iron and phosphorus. Moreover, the investigations focused on finding the differences between the levels of iron and zinc in other tissues: the liver, spleen and serum of the examined rats. Fifty-six female Sprague-Dawley rats, 40 days old, were divided into four groups, regardless of the diets: standard (77mg Zn kg/food), zinc (4.6mg/mL via gavage), zinc (4.6mg/mL) plus resveratrol (0.2mg/kgbw), and zinc (4.6mg/mL) plus genistein (0.2mg/kgbw) for a period from 40 days until 20 weeks of age. The study rats were also treated with 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) to induce mammary carcinogenesis. The applied diet and the advanced mammary cancer did not affect macrometric parameters of the rats' bones, but they strongly affected their mineral content. It was found that mammary cancer, irrespectively of the applied diet, significantly modified the iron level in the femur, liver, spleen and serum of the examined rats. In addition, zinc supplementation significantly lowered the levels of calcium, magnesium and phosphorus in the femur of rats with mammary cancer as compared with respective levels in the control group. So, it was found that additional supplementation with zinc, which is generally considered to be an antioxidant, with the co-existing mammary carcinoma, increased the unfavorable changes as concerns the stability of bone tissue. The appropriate combination of zinc and phytoestrogens (resveratrol or genistein) could help prevent or slow bone loss associated with a range of skeletal disorders in breast cancer.

  5. Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice

    PubMed Central

    Guerrero-Bosagna, Carlos M; Sabat, Pablo; Valdovinos, Fernanda S; Valladares, Luis E; Clark, Susan J

    2008-01-01

    Background Developmental effects of exposure to endocrine disruptors can influence adult characters in mammals, but could also have evolutionary consequences. The aim of this study was to simulate an environmental exposure of an experimental population of mice to high amounts of nutritional phytoestrogens and to evaluate parameters of relevance for evolutionary change in the offspring. The effect of a continuous pre- and post-natal exposure to high levels of dietary isoflavones was evaluated on sexual maturity, morphometric parameters and DNA methylation status in mice. Adult mice male/female couples were fed ad libitum either with control diet (standard laboratory chow) or ISF diet (control diet plus a soy isoflavone extract at 2% (w/w) that contained the phytoestrogens genistein and daidzein). In the offspring we measured: i) the onset of vaginal opening (sexual maturation) in females, ii) weight and size in all pups at 7, 14, 21 and 42 days post-natal (dpn) and iii) DNA methylation patterns in skeletal α-actin (Acta1), estrogen receptor-α and c-fos in adults (42 dpn). Results Vaginal opening was advanced in female pups in the ISF group, from 31.6 ± 0.75 dpn to 25.7 ± 0.48. No differences in size or weight at ages 7, 14 or 21 dpn were detected between experimental groups. Nevertheless, at age 42 dpn reduced size and weight were observed in ISF pups, in addition to suppression of normal gender differences in weight seen in the control group (males heavier that females). Also, natural differences seen in DNA methylation at Acta1 promoter in the offspring originated in the control group were suppressed in the ISF group. Acta1 is known to be developmentally regulated and related to morphomotric features. Conclusion This study demonstrates in mammals that individuals from a population subjected to a high consumption of isoflavones can show alterations in characters that may be of importance from an evolutionary perspective, such as epigenetic and morphometric

  6. Optical Stimulation of Neurons

    PubMed Central

    Thompson, Alexander C.; Stoddart, Paul R.; Jansen, E. Duco

    2014-01-01

    Our capacity to interface with the nervous system remains overwhelmingly reliant on electrical stimulation devices, such as electrode arrays and cuff electrodes that can stimulate both central and peripheral nervous systems. However, electrical stimulation has to deal with multiple challenges, including selectivity, spatial resolution, mechanical stability, implant-induced injury and the subsequent inflammatory response. Optical stimulation techniques may avoid some of these challenges by providing more selective stimulation, higher spatial resolution and reduced invasiveness of the device, while also avoiding the electrical artefacts that complicate recordings of electrically stimulated neuronal activity. This review explores the current status of optical stimulation techniques, including optogenetic methods, photoactive molecule approaches and infrared neural stimulation, together with emerging techniques such as hybrid optical-electrical stimulation, nanoparticle enhanced stimulation and optoelectric methods. Infrared neural stimulation is particularly emphasised, due to the potential for direct activation of neural tissue by infrared light, as opposed to techniques that rely on the introduction of exogenous light responsive materials. However, infrared neural stimulation remains imperfectly understood, and techniques for accurately delivering light are still under development. While the various techniques reviewed here confirm the overall feasibility of optical stimulation, a number of challenges remain to be overcome before they can deliver their full potential. PMID:26322269

  7. Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats.

    PubMed

    Baeza, Isabel; Fdez-Tresguerres, Jesús; Ariznavarreta, Carmen; De la Fuente, Mónica

    2010-12-01

    Ovariectomy constitutes a commonly used model in rats and mice for human menopause. After ovariectomy, an imbalance between oxidant production and antioxidant levels appears in favour of the former, with increased oxidative stress and consequently an acceleration of ageing. In the present work, the levels of reduced glutathione (GSH), a relevant antioxidant, and oxidized glutathione (GSSG), an oxidant compound, as well as lipid peroxidation (through malondialdehyde (MDA) levels), were studied in liver, heart, kidney and spleen homogenates of old (24 months of age) unovariectomized and ovariectomized female Wistar rats. The results showed a significant increase of the GSSG/GSH ratio, a marker of oxidative stress, and higher MDA production in all the studied organs of ovariectomized rats as compared with unovariectomized animals. These data confirm the idea that ovariectomy accelerates the ageing process. Administration of growth hormone (GH), melatonin (MEL) and oestrogens (OE), as well as soybean phytoestrogens (PE) for 10 weeks, between 22 and 24 months of age, was able to decrease oxidative stress in the investigated organs of ovariectomized old rats, therefore slowing down the ageing process in those animals.

  8. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine.

    PubMed

    Possemiers, Sam; Bolca, Selin; Grootaert, Charlotte; Heyerick, Arne; Decroos, Karel; Dhooge, Willem; De Keukeleire, Denis; Rabot, Sylvie; Verstraete, Willy; Van de Wiele, Tom

    2006-07-01

    Hops, an essential beer ingredient, are a source of prenylflavonoids, including 8-prenylnaringenin (8-PN), one of the most potent phytoestrogens. Because 8-PN concentrations in beers are generally low, its health effects after moderate beer consumption were considered negligible. However, human intestinal microbiota may activate up to 4 mg/L isoxanthohumol (IX) in beer into 8-PN. Depending on interindividual differences in the intestinal transformation potential, this conversion could easily increase the 8-PN exposure 10-fold upon beer consumption. Here, we present a further investigation of the process both in vitro and in vivo. In vitro experiments with the dynamic SHIME model showed that hop prenylflavonoids pass unaltered through the stomach and small intestine and that activation of IX into 8-PN (up to 80% conversion) occurs only in the distal colon. In vitro incubations of 51 fecal samples from female volunteers with IX enabled us to separate the fecal microbiota into high (8 of 51), moderate (11 of 51) and slow (32 of 51) 8-PN producers, clearly illustrating an interindividual variability. Three women, selected from the respective groups, received a daily dose of 5.59 mg IX for 4 d. Intestinal IX activation and urinary 8-PN excretion were correlated (R(2) = 0.6417, P < 0.01). These data show that intestinal conversion of IX upon moderate beer consumption can lead to 8-PN exposure values that might fall within the range of human biological activity.

  9. Prenatal exposure to the phytoestrogen daidzein resulted in persistent changes in ovarian surface epithelial cell height, folliculogenesis, and estrus phase length in adult Sprague-Dawley rat offspring.

    PubMed

    Talsness, Chris; Grote, Konstanze; Kuriyama, Sergio; Presibella, Kenia; Sterner-Kock, Anja; Poça, Katia; Chahoud, Ibrahim

    2015-01-01

    Daidzein (DZ), an isoflavone with the potential to interfere with estrogen signaling, is found in soy products, which have gained popularity due to purported beneficial effects on the cardiovascular and skeletal systems and potential antineoplastic properties. However, the ingestion of phytoestrogens has been associated with impaired reproductive function in many species. The aim of this study was to determine the long-term effects on the ovaries of rat offspring exposed to DZ or ethinyl estradiol (EE) during prenatal development. Gravid rats were administered either vehicle or 5 or 60 mg DZ/kg body weight/d or 0.002 mg 17-α EE /kg body weight/d on gestational days 6-21. Ovarian-related endpoints were investigated during adulthood in female offspring. The mean cell height of the ovarian surface epithelium was significantly reduced in all treated groups. Alterations in folliculogenesis included increased follicular atresia, a reduction in secondary and tertiary follicle numbers, and cyst formation. An elevated prevalence of a slightly prolonged estrus phase was also observed. The morphological changes to the ovarian surface epithelium are consistent with an antiproliferative effect, while ovarian folliculogenesis was adversely affected. The effects of the high dose DZ were similar to those observed with 17-α EE. PMID:26039681

  10. Wedelolactone induces growth of breast cancer cells by stimulation of estrogen receptor signalling.

    PubMed

    Nehybova, Tereza; Smarda, Jan; Daniel, Lukas; Brezovsky, Jan; Benes, Petr

    2015-08-01

    Wedelolactone, a plant coumestan, was shown to act as anti-cancer agent for breast and prostate carcinomas in vitro and in vivo targeting multiple cellular proteins including androgen receptors, 5-lipoxygenase and topoisomerase IIα. It is cytotoxic to breast, prostate, pituitary and myeloma cancer cell lines in vitro at μM concentrations. In this study, however, a novel biological activity of nM dose of wedelolactone was demonstrated. Wedelolactone acts as agonist of estrogen receptors (ER) α and β as demonstrated by transactivation of estrogen response element (ERE) in cells transiently expressing either ERα or ERβ and by molecular docking of this coumestan into ligand binding pocket of both ERα and ERβ. In breast cancer cells, wedelolactone stimulates growth of estrogen receptor-positive cells, expression of estrogen-responsive genes and activates rapid non-genomic estrogen signalling. All these effects can be inhibited by pretreatment with pure ER antagonist ICI 182,780 and they are not observed in ER-negative breast cancer cells. We conclude that wedelolactone acts as phytoestrogen in breast cancer cells by stimulating ER genomic and non-genomic signalling pathways.

  11. Peripheral nerve stimulation: definition.

    PubMed

    Abejón, David; Pérez-Cajaraville, Juan

    2011-01-01

    Recently, there has been a tremendous evolution in the field of neurostimulation, both from the technological point of view and from development of the new and different indications. In some areas, such as peripheral nerve stimulation, there has been a boom in recent years due to the variations in the surgical technique and the improved results documented by in multiple published papers. All this makes imperative the need to classify and define the different types of stimulation that are used today. The confusion arises when attempting to describe peripheral nerve stimulation and subcutaneous stimulation. Peripheral nerve stimulation, in its pure definition, involves implanting a lead on a nerve, with the aim to produce paresthesia along the entire trajectory of the stimulated nerve.

  12. Stimulant Use Disorders.

    PubMed

    Park, Taryn M; Haning, William F

    2016-07-01

    Compared with other illicit substances, stimulants are not commonly used by adolescents; however, they represent a serious concern regarding substance use among youths. This article uses methamphetamine as a model for stimulant use in adolescents; cocaine and prescription stimulants are also mentioned. Methamphetamine use among adolescents and young adults is a serious health concern with potentially long-term physical, cognitive, and psychiatric consequences. Brain development and the effects of misusing stimulants align such that usage in adolescents can more dangerous than during adulthood. It seems helpful to keep in mind the differences between adolescents and young adults when implementing interventions. PMID:27338967

  13. Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/HeJ mice.

    PubMed

    McElwee, K J; Niiyama, S; Freyschmidt-Paul, P; Wenzel, E; Kissling, S; Sundberg, J P; Hoffmann, R

    2003-02-01

    Alopecia areata (AA) is a complex, multi-factorial disease where genes and the environment may affect susceptibility and severity. Diet is an environmental factor with the potential to influence disease susceptibility. We considered dietary soy (soya) oil content and the soy-derived phytoestrogen genistein as potential modifying agents for C3H/HeJ mouse AA. Normal haired C3H/HeJ mice were grafted with skin from spontaneous AA affected mice, a method previously shown to induce AA. Grafted mice were given one of three diets containing 1%, 5% or 20% soy oil and observed for AA development. In a separate study, mice on a 1% soy oil diet were injected with 1 mg of genistein three times per week for 10 weeks or received the vehicle as a control. Of mice on 1%, 5%, and 20% soy oil diets, 43 of 50 mice (86%), 11 of 28 mice (39%), and 2 of 11 mice (18%) developed AA, respectively. Four of 10 mice injected with genistein and 9 of 10 controls developed AA. Mice with AA had hair follicle inflammation consistent with observations for spontaneous mouse AA, but no significant association was observed between the extent of hair loss and diet or genistein injection. Mice that failed to develop AA typically experience white hair regrowth from their skin grafts associated with a moderate macrophage and dendritic cell infiltration. Soy oil and derivatives have previously been reported to modify inflammatory conditions. Hypothetically, soy oil compounds may act on C3H/HeJ mice through modulating estrogen-dependent mechanisms and/or inflammatory activity to modify AA susceptibility. PMID:12631244

  14. E-Screen evaluation of sugar beet feedstuffs in a case of reduced embryo transfer efficiencies in cattle: the role of phytoestrogens and zearalenone.

    PubMed

    Shappell, N W; Mostrom, M S; Lenneman, E M

    2012-04-01

    The E-Screen assay was used to evaluate the estrogenicity of sugar beet by-products obtained from a dairy farm experiencing low success rates of embryo transfer. The beet tailings had ~3-fold the estradiol equivalents of the pelleted beet pulp (3.9 and 1.2 μg estradiol equivalents or E(2)Eq/kg dry matter, respectively). Whole sugar beets, sugar beet pellets, and shreds from several Midwest US locations were also evaluated by E-Screen. All pellets examined were found to have some estrogenic activity (range ~0.1-2.0 μg E(2)Eq/kg DM) with a mean of 0.46 μg/kg dry matter and median of 0.28 μg/kg dry matter. Relative E(2)Eq ranked as follows: pellets > shreds > most unprocessed roots. Using recommended feeding levels and conservative absorption estimates (10%), the estrogenic activity in the original samples could result in blood estradiol equivalents ≥ those found at estrus (10 pg/mL, cows). Chemical analyses revealed no known phytoestrogens, but the estrogenic mycotoxin, zearalenone, was found in 15 of 21 samples. Of significance to those using the E-Screen are our findings that contradict previous reports: ß-sitosterol has no proliferative effect and genistein's glucuronidated form-genistin-is equal to genistein in proliferative effect. The latter is the result of deconjugation of genistin to genistein in the presence of fetal bovine serum (determined by LC MSMS). These data show the usefulness and caveats of the E-Screen in evaluation of feedstuffs, and indicate a potential for sugar beet by-products to contain zearalenone at concentrations that may impact reproduction. PMID:22350809

  15. Phytoestrogens regulate mRNA and protein levels of guanine nucleotide-binding protein, beta-1 subunit (GNB1) in MCF-7 cells.

    PubMed

    Naragoni, Srivatcha; Sankella, Shireesha; Harris, Kinesha; Gray, Wesley G

    2009-06-01

    Phytoestrogens (PEs) are non-steroidal ligands, which regulate the expression of number of estrogen receptor-dependent genes responsible for a variety of biological processes. Deciphering the molecular mechanism of action of these compounds is of great importance because it would increase our understanding of the role(s) these bioactive chemicals play in prevention and treatment of estrogen-based diseases. In this study, we applied suppression subtractive hybridization (SSH) to identify genes that are regulated by PEs through either the classic nuclear-based estrogen receptor or membrane-based estrogen receptor pathways. SSH, using mRNA from genistein (GE) treated MCF-7 cells as testers, resulted in a significant increase in GNB1 mRNA expression levels as compared with 10 nM 17beta estradiol or the no treatment control. GNB1 mRNA expression was up regulated two- to fivefold following exposure to 100.0 nM GE. Similarly, GNB1 protein expression was up regulated 12- to 14-fold. GE regulation of GNB1 was estrogen receptor-dependent, in the presence of the anti-estrogen ICI-182,780, both GNB1 mRNA and protein expression were inhibited. Analysis of the GNB1 promoter using ChIP assay showed a PE-dependent association of estrogen receptor alpha (ERalpha) and beta (ERbeta) to the GNB1 promoter. This association was specific for ERalpha since association was not observed when the cells were co-incubated with GE and the ERalpha antagonist, ICI. Our data demonstrate that the levels of G-protein, beta-1 subunit are regulated by PEs through an estrogen receptor pathway and further suggest that PEs may control the ratio of alpha-subunit to beta/gamma-subunits of the G-protein complex in cells. J. Cell. Physiol. 219: 584-594, 2009. (c) 2009 Wiley-Liss, Inc. PMID:19170076

  16. [Electromagnetic urological stimulator].

    PubMed

    Zaslavskiĭ AOi; Markarov, G S; Gelis, Iu S

    1997-01-01

    The paper deals with an electromagnetic urological stimulator which generates a modulated low-frequency electromagnetic field of nonthermal intensity and its brief technical data. It presents a treatment regimen for urolithiasis and recommendations how to use the above therapeutical agent to stimulate urinary function in patients with urolithiasis in order to inoperatively eliminate urinary calculi and sand which form following extracorporeal shockwave lithotripsy.

  17. Stimulating your appetite.

    PubMed

    Whitfield, L

    1998-01-01

    A number of legal and illegal drugs can help stimulate appetite and are used for people with HIV to prevent wasting. Stimulating hunger is important because lower calorie intake and poor absorption of nutrients are associated with wasting. The uses and potential drawbacks of marijuana, thalidomide (Synovir), Marinol, and Megace are described. PMID:11365223

  18. Development and validation of a GC-MS method for the evaluation of 17 endocrine disruptor compounds, including phytoestrogens and sitosterol, in coastal waters - their spatial and seasonal levels in Porto costal region (Portugal).

    PubMed

    Rocha, Maria João; Cruzeiro, Catarina; Rocha, Eduardo

    2013-06-01

    A gas chromatography with mass spectrometric detection (GC-MS) method was developed and optimized for the determination of 17 endocrine disrupting compounds (EDCs) in coastal water samples. The evaluated EDCs were from different origins and included estrogens, bisphenol A, alkylphenolethoxylates, alkylphenols, phytoestrogens and sitosterol (SITO). The EDCs were extracted from samples using Oasis HLB (Hydrophilic-Lipophilic Balance) cartridges and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) added with 1% trimethylchlorosilane (TMCS). The validation parameters revealed that this method was highly specific for all assayed compounds (>99%) and the linearity of the calibration curves showed a correlation higher than 0.99. The detection limits were at low ng/L level and the recovery rates were higher than 70%. The performance of the method was checked using coastal water samples taken every 2 months during 2009-2010 from the Douro River estuary and the Porto coastline (Portugal). These data revealed that approximately 98.0% of the analyzed compounds showed levels above their limits of detection (LODs). The measured estrogens (2-20 ng/L) and industrial pollutants (up to 1.1 μg/L) were in biologic hazardous concentrations. Besides, a clear seasonal pattern of fluctuation was established for phytoestrogens and SITO. The physicochemical data, namely the amounts of nitrates, nitrites and phosphorous, confirmed the low water quality of this area.

  19. Dichloromethane extracts of Sophora japonica L. stimulate osteoblast differentiation in mesenchymal stem cells.

    PubMed

    Yoon, Hyang-Jin; Seo, Cho-Rong; Kim, Miae; Kim, Young-Jun; Song, No-Joon; Jang, Woo-Seok; Kim, Byung-Joon; Lee, Jaehwan; Hong, Joung-Woo; Nho, Chu Won; Park, Kye Won

    2013-12-01

    Sophora japonica L. fruit prevents bone loss by inhibiting osteoclast activity. We hypothesized that S japonica L. extracts could promote osteoblast differentiation. To test this hypothesis, we investigated the effect of S japonica L. on osteoblast differentiation and identified the bioactive compound(s) from S japonica L. The mature fruit of S japonica L. was partitioned with ethanol, hexane, dichloromethane (DCM), ethyl acetate, and butanol, and their effects were tested on osteoblast differentiation of C3H10T1/2 cells. DCM fractionated extracts were identified as the most osteogenic fractions. DCM fractionated extracts dose-dependently stimulated alkaline phosphatase activity and matrix mineralization. The DCM fractions also induced expression of osteoblast markers such as alkaline phosphatase, osterix, and osteocalcin in C3H10T1/2 and primary bone marrow cells. Genistein was found abundantly in the DCM fractions. Furthermore, the genistein and DCM fractions similarly modulated the expression of estrogen target genes and were both active in transfection assays that measured estrogen agonistic activity. Finally, pharmacological inhibition by treatment with an estrogen receptor antagonist or specific inhibition of gene expression by small interference RNAs targeted to estrogen receptor-β abolished the effects of the DCM extracts, further supporting the idea that the genistein in the DCM extracts mediated the pro-osteogenic effects. Taken together, we identified genistein as the key phytoestrogen responsible for the effects of S japonica L. on osteoblast differentiation. PMID:24267045

  20. Optically stimulated luminescence dosimetry

    NASA Astrophysics Data System (ADS)

    McKeever, Stephen W. S.

    2001-09-01

    Models and the conceptual framework necessary for an understanding of optically stimulated luminescence (OSL) are described. Examples of various OSL readout schemes are described, along with examples of the use of OSL in radiation dosimetry.

  1. Deep brain stimulation

    MedlinePlus

    ... the brain The neurostimulator, which puts out the electric current. The stimulator is similar to a heart pacemaker . It is usually placed under the skin near the collarbone, but may be ... pulses travel from the neurostimulator, along the extension ...

  2. ACTH stimulation test

    MedlinePlus

    ... Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 102. Chernecky CC, Berger BJ. ACTH stimulation test - diagnostic. In: ... . 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  3. Geothermal Well Stimulation

    SciTech Connect

    Campbell, D. A.; Morris, C. W.; Sinclair, A. R.; Hanold, R. J.; Vetter, O. J.

    1981-03-01

    The stimulation of geothermal wells presents some new and challenging problems. Formation temperatures in the 300-600 F range can be expected. The behavior of stimulation fluids, frac proppants, and equipment at these temperatures in a hostile brine environment must be carefully evaluated before performance expectations can be determined. In order to avoid possible damage to the producing horizon of the formation, high temperature chemical compatibility between the in situ materials and the stimulation materials must be verified. Perhaps most significant of all, in geothermal wells the required techniques must be capable of bringing about the production of very large amounts of fluid. This necessity for high flow rates represents a significant departure from conventional petroleum well stimulation and demands the creation of very high near-wellbore permeability and/or fractures with very high flow conductivity.

  4. Changes in the histomorphometric and biomechanical properties of the proximal femur of ovariectomized rat after treatment with the phytoestrogens genistein and equol.

    PubMed

    Tezval, Mohammad; Sehmisch, Stephan; Seidlová-Wuttke, Dana; Rack, Thomas; Kolios, Leila; Wuttke, Wolfgang; Stuermer, Klaus Michael; Stuermer, Ewa Klara

    2010-02-01

    The isoflavonoids found in soy have attracted great interest as dietary phytoestrogens that might be effective for postmenopausal hormone replacement therapy. Special attention has been devoted to the hormonal effects of various isoflavonoids, like genistein (GEN) and daidzein's (DAID) potent metabolite, equol (EQ). Here we aimed to investigate the short-term effects of genistein and equol on the proximal femur of ovariectomized (OVX) rats. Forty-eight, 3-month-old female Sprague-Dawley rats were ovarectomized; after eight weeks the bilateral osteotomy and osteosynthesis (OS) of their tibiae was performed and the rats were randomly divided into the following four groups: OVX control group (C), treated with estradiol-17beta (E2) -benzoate (E; daily intake 0.086 mg/d per animal), genistein (GEN; daily intake 12.7 mg/d per animal) and equol (EQ; daily intake 4.65 mg/d per animal). At 5 weeks postoperatively (OS), the breaking test was performed on the trochanteric region of femur. Additionally, histomorphometric assessment, and trabecular and cortical bone microstructure analyses were performed. The relative gain of body weight (BW) in the EQ (24 %) group was significantly (p < 0.05) lower than in the C (33 %) and GEN (30 %) groups. After treatment for 5 weeks, the maximal load (F(max)) and yield load (yL) were higher (p < 0.05 for the weight-adapted results) in the E (188.4 N resp. 113.1 N) and EQ (177.3 N resp. 112 N) groups as compared to C (162.8 N resp. 109.1 N) and GEN (165.7 N resp. 108.8 N). In the histomorphometric tests the E- (trabecular area (Tb.Ar) = 74.93 %, trabecular nodes/mm(2) (N.Nd/mm(2)) = 48.65) and EQ-treated (Tb.Ar = 63.13 %, N.Nd/mm(2) = 43.72) animals showed significant improvement with regard to Tb.Ar and trabecular connectivity (N.Nd./mm(2)) in comparison to C (Tb.Ar = 46.84, N.Nd/mm(2) = 31.86) and GEN (Tb.Ar = 48.22 %, N.Nd/mm(2) = 34.15). There were no differences in relative cortical width (Ct.Wi) among the four groups. The treatment

  5. Vagus Nerve Stimulation

    PubMed Central

    Howland, Robert H.

    2014-01-01

    The vagus nerve is a major component of the autonomic nervous system, has an important role in the regulation of metabolic homeostasis, and plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferent and efferent pathways. Vagus nerve stimulation (VNS) refers to any technique that stimulates the vagus nerve, including manual or electrical stimulation. Left cervical VNS is an approved therapy for refractory epilepsy and for treatment resistant depression. Right cervical VNS is effective for treating heart failure in preclinical studies and a phase II clinical trial. The effectiveness of various forms of non-invasive transcutaneous VNS for epilepsy, depression, primary headaches, and other conditions has not been investigated beyond small pilot studies. The relationship between depression, inflammation, metabolic syndrome, and heart disease might be mediated by the vagus nerve. VNS deserves further study for its potentially favorable effects on cardiovascular, cerebrovascular, metabolic, and other physiological biomarkers associated with depression morbidity and mortality. PMID:24834378

  6. New York Canyon Stimulation

    SciTech Connect

    Raemy, Bernard

    2012-06-21

    The New York Canyon Stimulation Project was to demonstrate the commercial application of Enhanced Geothermal System techniques in Buena Vista Valley area of Pershing County, Nevada. From October 2009 to early 2012, TGP Development Company aggressively implemented Phase I of Pre-Stimulation and Site/Wellbore readiness. This included: geological studies; water studies and analyses and procurement of initial permits for drilling. Oversubscription of water rights and lack of water needed for implementation of EGS were identified and remained primary obstacles. Despite extended efforts to find alternative solutions, the water supply circumstances could not be overcome and led TGP to determine a "No Go" decision and initiate project termination in April 2012.

  7. Muscle Stimulation Technology

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Under a Goddard Space Flight Center contract, Electrologic of America was able to refine the process of densely packing circuitry on personal computer boards, providing significant contributions to the closed-loop systems for the Remote Manipulator System Simulator. The microcircuitry work was then applied to the StimMaster FES Ergometer, an exercise device used to stimulate muscles suffering from paralysis. The electrical stimulation equipment was developed exclusively for V-Care Health Systems, Inc. Product still commercially available as of March 2002.

  8. What does galvanic vestibular stimulation stimulate?

    PubMed

    Wardman, Daniel L; Fitzpatrick, Richard C

    2002-01-01

    The technique of galvanic vestibular stimulation (GVS) has been used for a long time. The stimulus produces stereotyped automatic postural and ocular responses. The mechanisms underlying these responses are not understood although they are commonly attributed to altered otolith output. Based on animal studies, it seems reasonable to assume that vestibular afferents from the otoliths and semicircular canals are affected similarly by GVS. With this assumption, and anatomical knowledge of the vestibular apparatus, a model is developed to describe the expected responses of vestibular afferents to percutaneous GVS and the physiological implications of this altered sensory signal. Bilateral bipolar GVS, the most commonly used technique, should produce a canal signal consistent with a strong ear-down roll towards the cathodal side, a smaller nose-to-cathode yaw, but no pitch signal. Bilateral bipolar GVS should also produce an otolith signal consistent with tilt towards the cathodal side or a translational acceleration towards the anodal side. The expected responses for other configurations of GVS are also described. The model appears consistent with published data on the ocular and postural responses to GVS, and suggests other testable hypotheses concerning postural, ocular and perceptual responses to GVS.

  9. Transcranial brain stimulation: closing the loop between brain and stimulation

    PubMed Central

    Karabanov, Anke; Thielscher, Axel; Siebner, Hartwig Roman

    2016-01-01

    Purpose of review To discuss recent strategies for boosting the efficacy of noninvasive transcranial brain stimulation to improve human brain function. Recent findings Recent research exposed substantial intra- and inter-individual variability in response to plasticity-inducing transcranial brain stimulation. Trait-related and state-related determinants contribute to this variability, challenging the standard approach to apply stimulation in a rigid, one-size-fits-all fashion. Several strategies have been identified to reduce variability and maximize the plasticity-inducing effects of noninvasive transcranial brain stimulation. Priming interventions or paired associative stimulation can be used to ‘standardize’ the brain-state and hereby, homogenize the group response to stimulation. Neuroanatomical and neurochemical profiling based on magnetic resonance imaging and spectroscopy can capture trait-related and state-related variability. Fluctuations in brain-states can be traced online with functional brain imaging and inform the timing or other settings of transcranial brain stimulation. State-informed open-loop stimulation is aligned to the expression of a predefined brain state, according to prespecified rules. In contrast, adaptive closed-loop stimulation dynamically adjusts stimulation settings based on the occurrence of stimulation-induced state changes. Summary Approaches that take into account trait-related and state-related determinants of stimulation-induced plasticity bear considerable potential to establish noninvasive transcranial brain stimulation as interventional therapeutic tool. PMID:27224087

  10. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  11. Optically stimulated luminescence dosimetry

    NASA Astrophysics Data System (ADS)

    McKeever, Stephen W.

    1999-02-01

    Optically Stimulated Luminescence (OSL) dosimetry is attractive to the health physics and dosimetry community due to its all-optical character, fast data acquisition and the avoidance of heating the detector. Until recently there was no luminescent material sensitive enough to radiation, and at the same time suitable for stimulation with visible light, for use in this application. However, anion-deficient aluminum oxide doped with carbon (Al2O3:C) appears to be not only an extremely sensitive thermoluminescence (TL) material, but is also well-suited to OSL applications. Several OSL readout protocols have been suggested, including cw-OSL, pulsed OSL (POSL), and 'delayed' OSL (DOSL). The paper discusses the physical mechanisms that give rise to the OSL signals and the dependence of these signals upon absorbed dose. Example applications of the use of OSL from Al2O3:C in environmental radiation and ultraviolet-B dosimetry are discussed.

  12. Sacral nerve stimulation.

    PubMed

    Matzel, K E; Stadelmaier, U; Besendörfer, M

    2004-01-01

    The current concept of recruiting residual function of an inadequate pelvic organ by electrostimulation involves stimulation of the sacral spinal nerves at the level of the sacral canal. The rationale for applying SNS to fecal incontinence was based on clinical observations of its effect on bowel habits and anorectal continence function in urologic patients (increased anorectal angulation and anal canal closure pressure) and on anatomic considerations: dissection demonstrated a dual peripheral nerve supply of the striated pelvic floor muscles that govern these functions. Because the sacral spinal nerve site is the most distal common location of this dual nerve supply, stimulating here can elicit both functions. Since the first application of SNS in fecal incontinence in 1994, this technique has been improved, the patient selection process modified, and the spectrum of indications expanded. At present SNS has been applied in more than 1300 patients with fecal incontinence limited.

  13. Cognitive stimulation in brainstorming.

    PubMed

    Dugosh, K L; Paulus, P B; Roland, E J; Yang, H C

    2000-11-01

    Research on group brainstorming has demonstrated that it is less effective for generating large numbers of ideas than individual brainstorming, yet various scholars have presumed that group idea sharing should enhance cognitive stimulation and idea production. Three experiments examined the potential of cognitive stimulation in brainstorming. Experiments 1 and 2 used a paradigm in which individuals were exposed to ideas on audiotape as they were brainstorming, and Experiment 3 used the electronic brainstorming paradigm. Evidence was obtained for enhanced idea generation both during and after idea exposure. The attentional set of the participant and the content of the exposure manipulation (number of ideas, presence of irrelevant information) influenced this effect. These results are consistent with a cognitive perspective on group brainstorming.

  14. Stimulated Raman photoacoustic imaging

    PubMed Central

    Yakovlev, Vladislav V.; Zhang, Hao F.; Noojin, Gary D.; Denton, Michael L.; Thomas, Robert J.; Scully, Marlan O.

    2010-01-01

    Achieving label-free, molecular-specific imaging with high spatial resolution in deep tissue is often considered the grand challenge of optical imaging. To accomplish this goal, significant optical scattering in tissues has to be overcome while achieving molecular specificity without resorting to extrinsic labeling. We demonstrate the feasibility of developing such an optical imaging modality by combining the molecularly specific stimulated Raman excitation with the photoacoustic detection. By employing two ultrashort excitation laser pulses, separated in frequency by the vibrational frequency of a targeted molecule, only the specific vibrational level of the target molecules in the illuminated tissue volume is excited. This targeted optical absorption generates ultrasonic waves (referred to as stimulated Raman photoacoustic waves) which are detected using a traditional ultrasonic transducer to form an image following the design of the established photoacoustic microscopy. PMID:21059930

  15. Raft River well stimulation experiments: geothermal reservoir well stimulation program

    SciTech Connect

    Not Available

    1980-08-01

    The Geothermal Reservoir Well Stimulation Program (GRWSP) performed two field experiments at the Raft River KGRA in 1979. Wells RRGP-4 and RRGP-5 were selected for the hydraulic fracture stimulation treatments. The well selection process, fracture treatment design, field execution, stimulation results, and pre- and post-job evaluations are presented.

  16. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  17. Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17{beta}-estradiol

    SciTech Connect

    Yanagihara, Nobuyuki . E-mail: yanagin@med.uoeh-u.ac.jp; Liu, Minhui; Toyohira, Yumiko; Tsutsui, Masato; Ueno, Susumu; Shinohara, Yuko; Takahashi, Kojiro; Tanaka, Kazumi

    2006-01-13

    Incubation of cultured bovine adrenal medullary cells with 17{beta}-estradiol (E{sub 2}) (0.3-100 nM) or membrane-impermeable E{sub 2}-bovine serum albumin (100 nM) acutely increased {sup 14}C-catecholamine synthesis from [{sup 14}C]tyrosine. The stimulatory effect of E{sub 2} was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E{sub 2} also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [{sup 3}H]E{sub 2} with apparent K {sub d}s of 3.2 and 106 nM, and B {sub max}s of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [{sup 3}H]E{sub 2} was most strongly inhibited by E{sub 2} and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E{sub 2} acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla.

  18. Stimulated parametric emission microscopy

    NASA Astrophysics Data System (ADS)

    Isobe, Keisuke; Kataoka, Shogo; Murase, Rena; Watanabe, Wataru; Higashi, Tsunehito; Kawakami, Shigeki; Matsunaga, Sachihiro; Fukui, Kiichi; Itoh, Kazuyoshi

    2006-01-01

    We propose a novel microscopy technique based on the four-wave mixing (FWM) process that is enhanced by two-photon electronic resonance induced by a pump pulse along with stimulated emission induced by a dump pulse. A Ti:sapphire laser and an optical parametric oscillator are used as light sources for the pump and dump pulses, respectively. We demonstrate that our proposed FWM technique can be used to obtain a one-dimensional image of ethanol-thinned Coumarin 120 solution sandwiched between a hole-slide glass and a cover slip, and a two-dimensional image of a leaf of Camellia sinensis.

  19. Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

    PubMed Central

    Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

    2016-01-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis. PMID:27588108

  20. Dorsal column stimulator applications

    PubMed Central

    Yampolsky, Claudio; Hem, Santiago; Bendersky, Damián

    2012-01-01

    Background: Spinal cord stimulation (SCS) has been used to treat neuropathic pain since 1967. Following that, technological progress, among other advances, helped SCS become an effective tool to reduce pain. Methods: This article is a non-systematic review of the mechanism of action, indications, results, programming parameters, complications, and cost-effectiveness of SCS. Results: In spite of the existence of several studies that try to prove the mechanism of action of SCS, it still remains unknown. The mechanism of action of SCS would be based on the antidromic activation of the dorsal column fibers, which activate the inhibitory interneurons within the dorsal horn. At present, the indications of SCS are being revised constantly, while new applications are being proposed and researched worldwide. Failed back surgery syndrome (FBSS) is the most common indication for SCS, whereas, the complex regional pain syndrome (CRPS) is the second one. Also, this technique is useful in patients with refractory angina and critical limb ischemia, in whom surgical or endovascular treatment cannot be performed. Further indications may be phantom limb pain, chronic intractable pain located in the head, face, neck, or upper extremities, spinal lumbar stenosis in patients who are not surgical candidates, and others. Conclusion: Spinal cord stimulation is a useful tool for neuromodulation, if an accurate patient selection is carried out prior, which should include a trial period. Undoubtedly, this proper selection and a better knowledge of its underlying mechanisms of action, will allow this cutting edge technique to be more acceptable among pain physicians. PMID:23230533

  1. Central nervous system stimulants.

    PubMed

    George, A J

    2000-03-01

    Three major types of CNS stimulant are currently abused in sport: amphetamine, cocaine and caffeine. Each drug type has its own characteristic mechanism of action on CNS neurones and their associated receptors and nerve terminals. Amphetamine is widely abused in sports requiring intense anaerobic exercise where it prolongs the tolerance to anaerobic metabolism. It is addictive, and chronic abuse causes marked behavioural change and sometimes psychosis. Major sports abusing amphetamine are cycling, American football, ice-hockey and baseball. Cocaine increases tolerance to intense exercise, yet most of its chronic effects on energy metabolism are negative. Its greatest effects seem to be as a central stimulant and the enhancement of short-term anaerobic exercise. It is highly addictive and can cause cerebral and cardiovascular fatalities. Caffeine enhances fatty acid metabolism leading to glucose conservation, which appears to benefit long-distance endurance events such as skiing. Caffeine is also addictive, and chronic abuse can lead to cardiac damage. Social abuse of each of the three drugs is often difficult to distinguish from their abuse in sport.

  2. A linearized current stimulator for deep brain stimulation.

    PubMed

    Shen, Ding-Lan; Chu, Yu-Jung

    2010-01-01

    This paper develops the front end of the stimulator which is applied in the implantable deep brain stimulation (DBS) for the therapy of Parkinson's disease. This stimulator adopts the low power switched-capacitor DAC accompanying with voltage-to-current transconductance amplifiers to obtain the adjustable output currents. The proposed distortion cancellation technique improves the linearity of the current stimulator. Multiple transconductance amplifiers sharing a single DAC save the circuit area. The biphasic stimulation waveform is generated from the bridge switching technique and the programmable pulse. This stimulation circuit provides the 0 approximately 165 microA current for a typical loading of 10 kΩ, 8 approximately 120 micros pulse width, and 126 approximately 244 Hz frequencies with a 0.35 microm CMOS technology at 3.3 V supply voltage. PMID:21096724

  3. Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats.

    PubMed

    Jankowski, Marek; Wang, Donghao; Danalache, Bogdan; Gangal, Marius; Gutkowska, Jolanta

    2010-08-01

    An increasing amount of evidence demonstrates the beneficial role of oxytocin (OT) in the cardiovascular system. Similar actions are attributed to genistein, an isoflavonic phytoestrogen. The treatment with genistein activates the OT system in the aorta of ovariectomized (OVX) Sprague-Dawley (SD) rats. The objective of this study was to determine the effects of low doses of genistein on the OT-induced effects in rat hypertension. The hypothesis tested was that treatment of OVX spontaneously hypertensive rats (SHRs) with genistein improves heart structure and heart work through a mechanism involving the specific OT receptor (OTR). OVX SHRs or SD rats were treated with genistein (in microg/g body wt sc, 10 days) in the presence or absence of an OT antagonist (OTA) [d(CH(2))(5), Tyr(Me)(2), Orn(8)]-vasotocin or a nonspecific estrogen receptor antagonist (ICI-182780). Vehicle-treated OVX rats served as controls. RT-PCR and Western blot analysis demonstrated that left ventricular (LV) OTR, downregulated by ovariectomy, increased in response to genistein. In SHRs or SD rats, this effect was blocked by OTA or ICI-182780 administration. The OTR was mainly localized in microvessels expressing the CD31 marker and colocalized with endothelial nitric oxide synthase. In SHRs, the genistein-stimulated OTR increases were associated with improved fractional shortening, decreased blood pressure (12 mmHg), decreased heart weight-to-body weight ratio, decreased fibrosis, and lowered brain natriuretic peptide in the LV. The prominent finding of the study is the detrimental effect of OTA treatment on the LV of SHRs. OTA treatment of OVX SHRs resulted in a dramatic worsening of ejection fractions and an augmented fibrosis. In conclusion, these results demonstrate that cardiac OTRs are involved in the regulation of cardiac function of OVX SHRs. The decreases of OTRs may contribute to cardiac pathology following menopause.

  4. Engagement Sensitive Visual Stimulation.

    PubMed

    Kumar, Deepesh; Dutta, Anirban; Das, Abhijit; Lahiri, Uttama

    2016-06-13

    Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one's performance. PMID:27478569

  5. Stimulated radiative laser cooling

    NASA Astrophysics Data System (ADS)

    Muys, P.

    2008-04-01

    Building a refrigerator based on the conversion of heat into optical energy is an ongoing engineering challenge. Under well-defined conditions, spontaneous anti-Stokes fluorescence of a dopant material in a host matrix is capable of lowering the host temperature. The fluorescence is conveying away a part of the thermal energy stored in the vibrational oscillations of the host lattice. In particular, applying this principle to the cooling of (solid-state) lasers opens up many potential device applications, especially in the domain of high-power lasers. In this paper, an alternative optical cooling scheme is outlined, leading to the radiative cooling of solid-state lasers. It is based on converting the thermal energy stored in the host into optical energy by means of a stimulated nonlinear process, rather than a spontaneous process. This should lead to better cooling efficiencies and a higher potential of applying the principle for device applications.

  6. Stimulated rotational Raman scattering

    NASA Astrophysics Data System (ADS)

    Parazzoli, C. G.; Rafanelli, G. L.; Capps, D. M.; Drutman, C.

    1989-03-01

    The effect of Stimulated Rotational Raman Scattering (SRRS) processes on high energy laser directed energy weapon systems was studied. The program had 3 main objectives; achieving an accurate description of the physical processes involved in SRRS; developing a numerical algorithm to confidently evaluate SRRS-induced losses in the propagation of high energy laser beams in the uplink and downlink segments of the optical trains of various strategic defense system scenarios; and discovering possible methods to eliminate, or at least reduce, the deleterious effects of SRRS on the energy deposition on target. The following topics are discussed: the motivation for the accomplishments of the DOE program; the Semiclassical Theory of Non-Resonant SRRS for Diatomic Homonuclear Molecules; and then the following appendices; Calculation of the Dipole Transition Reduced Matrix Element, Guided Tour of Hughes SRRS Code, Running the Hughes SRRS Code, and Hughes SRRS Code Listing.

  7. Myeloperoxidase Stimulates Neutrophil Degranulation.

    PubMed

    Grigorieva, D V; Gorudko, I V; Sokolov, A V; Kostevich, V A; Vasilyev, V B; Cherenkevich, S N; Panasenko, O M

    2016-08-01

    Myeloperoxidase, heme enzyme of azurophilic granules in neutrophils, is released into the extracellular space in the inflammation foci. In neutrophils, it stimulates a dose-dependent release of lactoferrin (a protein of specific granules), lysozyme (a protein of specific and azurophilic granules), and elastase (a protein of azurophilic granules). 4-Aminobenzoic acid hydrazide, a potent inhibitor of peroxidase activity of myeloperoxidase, produced no effect on neutrophil degranulation. Using signal transduction inhibitors (genistein, methoxyverapamil, wortmannin, and NiCl2), we demonstrated that myeloperoxidase-induced degranulation of neutrophils resulted from enzyme interaction with the plasma membrane and depends on activation of tyrosine kinases, phosphatidylinositol 3-kinases (PI3K), and calcium signaling. Myeloperoxidase modified by oxidative/halogenation stress (chlorinated and monomeric forms of the enzyme) lost the potency to activate neutrophil degranulation. PMID:27597056

  8. Engagement Sensitive Visual Stimulation

    PubMed Central

    Kumar, Deepesh; Dutta, Anirban; Das, Abhijit; Lahiri, Uttama

    2016-01-01

    Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one’s performance. PMID:27478569

  9. Spiral scan peripheral nerve stimulation.

    PubMed

    King, K F; Schaefer, D J

    2000-07-01

    Time-varying magnetic fields induce electric fields that can cause physiological stimulation. Stimulation has been empirically characterized as a function of dB/dt and duration based on experiments using trapezoidal and sinusoidal gradient waveforms with constant ramp time, amplitude, and direction. For two-dimensional (2D) spiral scans, the readout gradient waveforms are frequency- and amplitude-modulated sinusoids on two orthogonal axes in quadrature. The readout gradient waveform therefore rotates with amplitude and angular velocity that are generally not constant. It does not automatically follow that spiral stimulation thresholds can be predicted using available stimulation models. We scanned 18 normal volunteers with a 2D spiral scan and measured global thresholds for axial, sagittal, and coronal planes. We concluded that the stimulation model evaluated accurately predicts slew rate-limited spiral mean stimulation thresholds, if the effective ramp time is chosen to be the half-period at the end of the spiral readout.

  10. Hydromechanical stimulation of bioluminescent plankton.

    PubMed

    Blaser, Stefan; Kurisu, Futoshi; Satoh, Hiroyasu; Mino, Takashi

    2002-01-01

    The response of the bioluminescent dinoflagellate Pyrocystis fusiformis was investigated for different hydraulic conditions ('hydromechanical stimulation'). Pipe flow and oscillating shear produced luminescence, whereas changes in hydrostatic pressure were not stimulating. More intense fluid motion led to higher intensity, mainly due to a higher probability of cell response. The organism was also able to emit light in a glucose-salt mixture. The experiments suggest that the cells are effectively stimulated if the flow conditions change in time.

  11. Promotion of insulin-like growth factor-I production by sensory neuron stimulation; molecular mechanism(s) and therapeutic implications.

    PubMed

    Okajima, Kenji; Harada, Naoaki

    2008-01-01

    Insulin-like growth factor-I (IGF-I) plays various important roles in cellular proliferation, differentiation, survival and functions of the cell, thereby contributing to the maintenance of tissue integrity. Although it is well known that growth hormone (GH) increases serum IGF-I levels by stimulating the hepatic production, little is known about the mechanism by which local production of IGF-I in individual tissues is regulated. Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I and IGF-I mRNA in various organs via increased calcitonin gene-related peptide (CGRP) release in mice. This sensory neuron-mediated IGF-I production contributes to reducing reperfusion-induced liver injury through prevention of apoptosis in mice. Isoflavone, a phytoestrogen, increases CGRP production by increasing its transcription in sensory neurons. Administration of capsaicin and isoflavone increases IGF-I production in hair follicles, thereby promoting hair growth in mice and in volunteers with alopecia. Topical application of capsaicin increases dermal levels of IGF-I by stimulating sensory neurons in mice and increases facial skin elasticity in humans. Plasma and tissue levels of CGRP and IGF-I in spontaneously hypertensive rats (SHR) are lower than those in normotensive Wistar Kyoto rats (WKY), contributing to the development of hypertension, heart failure and insulin resistance in SHR. Administration of capsaicin increases CGRP and IGF-I levels in plasma, kidneys and the heart in SHR to WKY levels, and normalizes mean arterial blood pressure in SHR. Since administration of GH or IGF-I has some deleterious effects, pharmacological stimulation of sensory neurons leading to increased tissue IGF-I levels might be a novel therapeutic strategy for various pathologic conditions.

  12. Optically stimulated differential impedance spectroscopy

    DOEpatents

    Maxey, Lonnie C; Parks, II, James E; Lewis, Sr., Samuel A; Partridge, Jr., William P

    2014-02-18

    Methods and apparatuses for evaluating a material are described. Embodiments typically involve use of an impedance measurement sensor to measure the impedance of a sample of the material under at least two different states of illumination. The states of illumination may include (a) substantially no optical stimulation, (b) substantial optical stimulation, (c) optical stimulation at a first wavelength of light, (d) optical stimulation at a second wavelength of light, (e) a first level of light intensity, and (f) a second level of light intensity. Typically a difference in impedance between the impedance of the sample at the two states of illumination is measured to determine a characteristic of the material.

  13. Electrical stimulation: a societal perspective.

    PubMed

    Gater, D R; McDowell, S M; Abbas, J J

    2000-01-01

    Societal perspective on functional electrical stimulation is colored by media influence, popular thought, and political climate as much as by the science that supports it. The purpose of this article is to examine how these influences facilitate or inhibit the application of electrical stimulation in today's world and to describe the challenges facing the use of electrical stimulation in the future. Emphasis will be placed on perceived need, cost, and available resources and how these factors must be addressed to utilize functional electrical stimulation successfully in society.

  14. Atomic oxygen stimulated outgassing

    NASA Technical Reports Server (NTRS)

    Linton, Roger C.; Reynolds, John M.

    1991-01-01

    The passive Long Duration Exposure Facility (LDEF) Experiment A0034, Atomic Oxygen Simulated Outgassing, consisted of two identical one-sixth tray modules, exposing selected thermal control coatings to atomic oxygen and the combined space environment on the leading edge and, for reference, to the relative wake environment on the trailing edge. Optical mirrors were included adjacent to the thermal coatings for deposition of outgassing products. Ultraviolet grade windows and metal covers were provided for additional assessment of the effects of the various environmental factors. Preliminary results indicate that orbital atomic oxygen is both a degrading and a optically restorative factor in the thermo-optical properties of selected thermal coatings. There is evidence of more severe optical degradation on collector mirrors adjacent to coatings that were exposed to the RAM-impinging atomic oxygen. This evidence of atomic oxygen stimulated outgassing is discussed in relation to alternative factors that could affect degradation. The general effects of the space environment on the experiment hardware as well as the specimens are discussed.

  15. EOR by stimulated microflora

    SciTech Connect

    Svarovskaya, L.I.; Altunina, L.K.; Rozhenkova, Z.A.; Bulavin, V.D.

    1995-12-31

    A combined microbiological and physico-chemical method for EOR has been developed for flooded West Siberia oil fields with formation temperature of 45{degrees}-95{degrees}C (318-365K). Formation water includes rich and various biocenoses numbering up to 2 x 10{sup 7} cells per ml. Representatives of genera, i.e, Pseudomonas, Bacillus, Actinomyces, Micrococcus, Mycobacterium, Sarcina, etc. were found to be the most widely distributed microorganisms. The method is based on injection of systems exhibiting high oil displacing capacity and at the same time being an additional nitrous nutrient for endemic populations of microorganisms. Their injection into formation water favors biomass growth by 4-6 orders and promotes syntheses of biosurfactants, biopolymers, acids, etc., and gaseous products. The features of residual oil displacement have been studied on laboratory models using a combined microbiological and physico-chemical method. A curve for the yield of residual oil is presented by two peaks. The first peak is stipulated by the washing action of oil displacement system, and the second one by the effect of metabolites produced at stimulation of biogenic processes. Oil displacement index increases by 15%-30%.

  16. Subliminal Stimulation: Hoax or Reality?

    ERIC Educational Resources Information Center

    Trank, Douglas M.

    Subliminal stimulation is defined as that which is perceived by an individual below the threshold of awareness or cognizance. This article traces the history of research in subliminal stimulation to illustrate that under certain circumstances and conditions, this behavioral phenomenon does occur. Although subliminal stimuli do affect human…

  17. Stimulating Language: Insights from TMS

    ERIC Educational Resources Information Center

    Devlin, Joseph T.; Watkins, Kate E.

    2007-01-01

    Fifteen years ago, Pascual-Leone and colleagues used transcranial magnetic stimulation (TMS) to investigate speech production in pre-surgical epilepsy patients and in doing so, introduced a novel tool into language research. TMS can be used to non-invasively stimulate a specific cortical region and transiently disrupt information processing. These…

  18. Nanomaterial-Enabled Neural Stimulation.

    PubMed

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed.

  19. Nanomaterial-Enabled Neural Stimulation

    PubMed Central

    Wang, Yongchen; Guo, Liang

    2016-01-01

    Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

  20. Vagal Nerve Stimulation Therapy: What Is Being Stimulated?

    PubMed Central

    Kember, Guy; Ardell, Jeffrey L.; Armour, John A.; Zamir, Mair

    2014-01-01

    Vagal nerve stimulation in cardiac therapy involves delivering electrical current to the vagal sympathetic complex in patients experiencing heart failure. The therapy has shown promise but the mechanisms by which any benefit accrues is not understood. In this paper we model the response to increased levels of stimulation of individual components of the vagal sympathetic complex as a differential activation of each component in the control of heart rate. The model provides insight beyond what is available in the animal experiment in as much as allowing the simultaneous assessment of neuronal activity throughout the cardiac neural axis. The results indicate that there is sensitivity of the neural network to low level subthreshold stimulation. This leads us to propose that the chronic effects of vagal nerve stimulation therapy lie within the indirect pathways that target intrinsic cardiac local circuit neurons because they have the capacity for plasticity. PMID:25479368

  1. DISRUPTED FEMALE REPRODUCTIVE PHYSIOLOGY FOLLOWING NEONATAL EXPOSURE TO PHYTOESTROGENS OR ESTROGEN SPECIFIC LIGANDS IS ASSOCIATED WITH DECREASED GNRH ACTIVATION AND KISSPEPTIN FIBER DENSITY IN THE HYPOTHALAMUS

    PubMed Central

    Bateman, Heather L.; Patisaul, Heather B.

    2008-01-01

    It is well established that estrogen administration during neonatal development can advance pubertal onset and prevent the maintenance of regular estrous cycles in female rats. This treatment paradigm also eliminates the preovulatory rise of gonadotropin releasing hormone (GnRH). It remains unclear, however, through which of the two primary forms of the estrogen receptor (ERα or ERβ) this effect is mediated. It is also unclear whether endocrine disrupting compounds (EDCs) can produce similar effects. Here we compared the effect of neonatal exposure to estradiol benzoate (EB), the ERα specific agonist 1,3,5-tris(4-Hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), the ERβ specific agonist diarylpropionitrile (DPN) and the naturally occurring EDCs genistein (GEN) and equol (EQ) on pubertal onset, estrous cyclicity, GnRH activation, and kisspeptin content in the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. Vaginal opening was significantly advanced by EB and GEN. By ten weeks post-puberty, irregular estrous cycles were observed in all groups except the control group. GnRH activation, as measured by the percentage of immunopositive GnRH neurons that were also immunopositive for Fos, was significantly lower in all treatment groups except the DPN group compared to the control group. GnRH activation was absent in the PPT group. These data suggest that neonatal exposure to EDCs can suppress GnRH activity in adulthood, and that ERα plays a pivotal role in this process. Kisspeptins (KISS) have recently been characterized to be potent stimulators of GnRH secretion. Therefore we quantified the density of KISS immunolabeled fibers in the AVPV and ARC. In the AVPV, KISS fiber density was significantly lower in the EB and GEN groups compared to the control group but only in the EB and PPT groups in the ARC. The data suggest that decreased stimulation of GnRH neurons by KISS could be a mechanism by which EDCs can impair female reproductive function. PMID:18656497

  2. Electrical stimulation in exercise training

    NASA Technical Reports Server (NTRS)

    Kroll, Walter

    1994-01-01

    Electrical stimulation has a long history of use in medicine dating back to 46 A.D. when the Roman physician Largus found the electrical discharge of torpedo fishes useful in the treatment of pain produced by headache and gout. A rival Greek physician, Dioscorides, discounted the value of the torpedo fish for headache relief but did recommend its use in the treatment of hemorrhoids. In 1745, the Leyden jar and various sized electrostatic generators were used to treat angina pectoris, epilepsy, hemiplegia, kidney stones, and sciatica. Benjamin Franklin used an electrical device to treat successfully a young woman suffering from convulsive fits. In the late 1800's battery powered hydroelectric baths were used to treat chronic inflammation of the uterus while electrified athletic supporters were advertised for the treatment of male problems. Fortunately, such an amusing early history of the simple beginnings of electrical stimulation did not prevent eventual development of a variety of useful therapeutic and rehabilitative applications of electrical stimulation. Over the centuries electrical stimulation has survived as a modality in the treatment of various medical disorders with its primary application being in the rehabilitation area. Recently, a surge of new interest in electrical stimulation has been kindled by the work of a Russian sport scientist who reported remarkable muscle strength and endurance improvements in elite athletes. Yakov Kots reported his research on electric stimulation and strength improvements in 1977 at a Canadian-Soviet Exchange Symposium held at Concordia University in Montreal. Since then an explosion of new studies has been seen in both sport science and in medicine. Based upon the reported works of Kots and the present surge of new investigations, one could be misled as to the origin of electrical stimulation as a technique to increase muscle strength. As a matter of fact, electric stimulation has been used as a technique to improve

  3. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, J.W.

    1995-05-09

    A device is described for stimulating bone tissue by applying a low level alternating current signal directly to the patient`s skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures. 5 figs.

  4. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, James W.

    1995-01-01

    A device for stimulating bone tissue by applying a low level alternating current signal directly to the patient's skin. A crystal oscillator, a binary divider chain and digital logic gates are used to generate the desired waveforms that reproduce the natural electrical characteristics found in bone tissue needed for stimulating bone growth and treating osteoporosis. The device, powered by a battery, contains a switch allowing selection of the correct waveform for bone growth stimulation or osteoporosis treatment so that, when attached to the skin of the patient using standard skin contact electrodes, the correct signal is communicated to the underlying bone structures.

  5. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner.

    PubMed

    Allred, C D; Allred, K F; Ju, Y H; Virant, S M; Helferich, W G

    2001-07-01

    We have demonstrated that the isoflavone, genistein, stimulates growth of estrogen-dependent human breast cancer (MCF-7) cells in vivo (C. Y. Hsieh et al., Cancer Res., 58: 3833-3838, 1998). The isoflavones are a group of phytoestrogens that are present in high concentrations in soy. Whether consumption of genistein from soy protein will have similar effects on estrogen-dependent tumor growth as pure genistein has not been investigated in the athymic mouse tumor implant model. Depending on processing, soy protein isolates vary widely in concentrations of genistein. We hypothesize that soy isolates containing different concentrations of genistein will stimulate the growth of estrogen-dependent cells in vivo in a dose-dependent manner. To test this hypothesis we conducted experiments in which these soy protein isolates were fed to athymic mice implanted s.c. with estrogen-dependent tumors. Genistein content (aglycone equivalent) of the soy isolate diets were 15, 150, or 300 ppm. Positive (with 17beta-estradiol pellet implant) and negative (no 17beta-estradiol) control groups received casein-based (isoflavone-free) diets. Tumor size was measured weekly. At completion of the study animals were killed and tumors collected for evaluation of cellular proliferation and estrogen-dependent gene expression. Incorporation of bromodeoxyuridine into cellular DNA was used as an indicator of cell proliferation, and pS2 mRNA was used as an estrogen-responsive gene. Soy protein diets containing varying amounts of genistein increased estrogen-dependent tumor growth in a dose-dependent manner. Cell proliferation was greatest in tumors of animals given estrogen or dietary genistein (150 and 300 ppm). Expression of pS2 was increased in tumors from animals consuming dietary genistein (150 and 300 ppm). Here we present new information that soy protein isolates containing increasing concentrations of genistein stimulate the growth of estrogen-dependent breast cancer cells in vivo in a dose

  6. Magnetically stimulated fluid flow patterns

    ScienceCinema

    Martin, Jim; Solis, Kyle

    2016-07-12

    Sandia National Laboratories' Jim Martin and Kyle Solis explain research on the effects of magnetic fields on fluid flows and how they stimulate vigorous flows. Fluid flow is a necessary phenomenon in everything from reactors to cooling engines in cars.

  7. Demultiplexer circuit for neural stimulation

    DOEpatents

    Wessendorf, Kurt O; Okandan, Murat; Pearson, Sean

    2012-10-09

    A demultiplexer circuit is disclosed which can be used with a conventional neural stimulator to extend the number of electrodes which can be activated. The demultiplexer circuit, which is formed on a semiconductor substrate containing a power supply that provides all the dc electrical power for operation of the circuit, includes digital latches that receive and store addressing information from the neural stimulator one bit at a time. This addressing information is used to program one or more 1:2.sup.N demultiplexers in the demultiplexer circuit which then route neural stimulation signals from the neural stimulator to an electrode array which is connected to the outputs of the 1:2.sup.N demultiplexer. The demultiplexer circuit allows the number of individual electrodes in the electrode array to be increased by a factor of 2.sup.N with N generally being in a range of 2-4.

  8. Magnetically stimulated fluid flow patterns

    SciTech Connect

    Martin, Jim; Solis, Kyle

    2014-03-06

    Sandia National Laboratories' Jim Martin and Kyle Solis explain research on the effects of magnetic fields on fluid flows and how they stimulate vigorous flows. Fluid flow is a necessary phenomenon in everything from reactors to cooling engines in cars.

  9. Evoked response to taste stimulations.

    PubMed

    Wada, Masashi

    2005-01-01

    For the recording of gustatory evoked responses, the tip of a stimulator is pressed vertically on one side of the tongue until the trigger pulses are generated by a switch attached to the bottom of the stimulator. According to our results, no detectable response was observed in the absence of taste. The positive waves were distinguishable by using the technique of superimposition before averaging, and the positive wave was made clearer by averaging.

  10. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    The following are included: review of available data from previous fracturing stimulation operations, stimulation process variables, fracturing fluid design, hydraulic fracture design, stimulation case histories, and selected bibliography. (MHR)

  11. 95 stimulations in 63 wells

    SciTech Connect

    Horton, A.I.

    1982-02-01

    Since 1976, extensive studies on the nature of the Eastern gas shales and the production potential from stimulated shale wells have been conducted through joint efforts of industry and the Department of Energy (DOE). Prior to development of this project, the conventional method of stimulating the shales was borehole shooting, and conventional hydraulic fracturing of the shale was just beginning. DOE-industry investigations under the Eastern Gas Shales Project have experimented with other types of stimulations, including massive hydraulic fracturing, foam fracturing, cryogenic fracturing, chemical explosives, and novel treatments. Two of the latter have used (1) nitrogen and (2) oil assisted with nitrogen. Two other treatments, which were unsuccessful, were (1) an open hole packer-stage frac and (2) a kerosene frac. These were operational and conceptual failures. Details of the stimulations and production data, where available, have been complied and studied. The experience that has been gained may prove helpful to those considering stimulation technology in future well drilling ventures in the shale. However, the limited data available in regions of similar geologic factors preclude a thorough analysis of stimulation effectiveness.

  12. Brain Stimulation for Torsion Dystonia

    PubMed Central

    Fox, Michael D.; Alterman, Ron L.

    2016-01-01

    Dystonia is a heterogeneous neurological disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly utilized. Here we review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation. Strong (level B) evidence supports the use of deep brain stimulation (DBS) for the treatment of primary generalized or segmental dystonia, especially DYT-1, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer’s cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson’s disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques including epidural cortical stimulation and noninvasive brain stimulation have been investigated, but generally report smaller effect sizes in a more limited number of patients. Recent advances relevant to patient selection, surgical approach, DBS programming, and mechanism of action are discussed. PMID:25894231

  13. Early Intervention with an Estrogen Receptor β-Selective Phytoestrogenic Formulation Prolongs Survival, Improves Spatial Recognition Memory, and Slows Progression of Amyloid Pathology in a Female Mouse Model of Alzheimer’s Disease

    PubMed Central

    Zhao, Liqin; Mao, Zisu; Chen, Shuhua; Schneider, Lon S.; Brinton, Roberta D.

    2014-01-01

    Our recent developments have yielded a novel phytoestrogenic formulation, referred to as the phyto-β-SERM formulation, which exhibits an 83-fold binding selectivity for the estrogen receptor subtype β (ERβ) over ERα. Earlier studies indicate that the phyto-β-SERM formulation is neuroprotective and promotes estrogenic mechanisms in the brain while devoid of feminizing activity in the periphery. Further investigation in a mouse model of human menopause indicates that chronic exposure to the phyto-β-SERM formulation at a clinically relevant dosage prevents/alleviates menopause-related climacteric symptoms. This study assessed the efficacy, in an early intervention paradigm, of the phyto-β-SERM formulation in the regulation of early stages of physical and neurological changes associated with Alzheimer’s disease (AD) in a female triple transgenic mouse model of AD. Results demonstrated that, when initiated prior to the appearance of AD pathology, a 9-month dietary supplementation with the phyto-β-SERM formulation promoted physical health, prolonged survival, improved spatial recognition memory, and attenuated amyloid-β deposition and plaque formation in the brains of treated AD mice. In comparison, dietary supplementation of a commercial soy extract preparation showed no effect on cognitive measures, although it appeared to have a positive impact on amyloid pathology. In overall agreement with the behavioral and histological outcomes, results from a gene expression profiling analysis offered insights on the underlying molecular mechanisms associated with the two dietary treatments. In particular, the data suggests that there may be a crosstalk between ERβ and glycogen synthase kinase 3 signaling pathways that could play a role in conferring ERβ-mediated neuroprotection against AD. Taken together, these results support the therapeutic potential of the phyto-β-SERM formulation for prevention and/or early intervention of AD, and warrants further

  14. R & D of an Innovative Composite Scaffold Incorporated with Phytoestrogenic Icaritin for Treatment of Steroid-associated Osteonecrosis Lesion in Rabbits

    NASA Astrophysics Data System (ADS)

    Xie, Xinhui

    Bone defect is a common orthopaedic problem caused by many pathologic disorders such as tumor, trauma or metabolic diseases, including osteonecrosis (ON). ON is a disabling clinical condition characterized by the death of osteocytes, aggregation of marrow fat cells, a decrease in activity of bone marrow stem cells (BMSCs) pool, and degeneration of trabecular bone matrix, which affect more frequently young adults that usually leads to bone and articular cartilage destruction in joints, especially in hip and knee. High dose of steroid is one of the risk factors associated with ON, which sometimes is used for treatment of some medical conditions such as systemic lupus erythematosus (SLE), organ transplantation, asthma, rheumatologic arthritis (RA), and severe acute respiratory syndrome (SARS). Core decompression has been efficacious for treatment of early ON stages when the necrotic lesion is still small in size. However, ON lesion, weakens the cancellous bone within and adjacent to the necrotic region. Thus orthopaedic challenges in repair for steroid-associated ON lesion after core decompression may include the impaired osteogenic potential of stem-cell-pool under the influence of pulsed steroid and lack of platform for bone or/and neovascularization ingrowth after removal of large size necrotic bone. The proposed strategies for treatment of steroid-associated ON lesion are to provide biocompatible scaffold with required structure to fill the defect area after core decompression and osteogenic stimulator facilitating the repair of ON lesion. Previous works show that the PLGA (poly-lactic glycolic acid) and TCP (tricalcium phosphate) have good biocompatibility, osteoconduction and biodegradation to be used in bone defect repair, however no significant osteopromotive effects. Many endogenous factors are osteopromotive and also eventually osteoinductive, such as bone morphogenic proteins (BMPs). As an extraneous molecular, Icaritin, a small molecule derived from

  15. Theoretical investigation on the pumping effect of stimulated Brillouin scattering on stimulated Raman scattering in water

    NASA Astrophysics Data System (ADS)

    Shi, J.; Chen, X.; Ouyang, M.; Gong, W.; Su, Y.; Liu, D.

    2012-02-01

    The pumping effect of stimulated Brillouin scattering on stimulated Raman scattering is investigated theoretically through the coupled wave equations of stimulated Brillouin scattering and stimulated Raman scattering. The numerical simulations are in agreement with the experimental results. They indicate that the backward stimulated Raman scattering is excited and amplified collectively by both pump laser and stimulated Brillouin scattering.

  16. Emerging neural stimulation technologies for bladder dysfunctions.

    PubMed

    Lee, Jee Woong; Kim, Daejeong; Yoo, Sangjin; Lee, Hyungsup; Lee, Gu-Haeng; Nam, Yoonkey

    2015-03-01

    In the neural engineering field, physiological dysfunctions are approached by identifying the target nerves and providing artificial stimulation to restore the function. Neural stimulation and recording technologies play a central role in this approach, and various engineering devices and stimulation techniques have become available to the medical community. For bladder control problems, electrical stimulation has been used as one of the treatments, while only a few emerging neurotechnologies have been used to tackle these problems. In this review, we introduce some recent developments in neural stimulation technologies including microelectrode array, closed-loop neural stimulation, optical stimulation, and ultrasound stimulation.

  17. Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.

    2003-01-01

    Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

  18. Electrical stimulation and motor recovery.

    PubMed

    Young, Wise

    2015-01-01

    In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical

  19. Improvements of Vaginal Atrophy without Systemic Side Effects after Topical Application of Pueraria mirifica, a Phytoestrogen-rich Herb, in Postmenopausal Cynomolgus Macaques

    PubMed Central

    JAROENPORN, Sukanya; URASOPON, Nontakorn; WATANABE, Gen; MALAIVIJITNOND, Suchinda

    2014-01-01

    The estrogenic efficacy of topical vaginal application of Pueraria mirifica extract (PM) on the restoration of vaginal atrophy, and the presence of any systemic side effects, were investigated in postmenopausal cynomolgus macaques. Twelve postmenopausal cynomolgus macaques, with complete cessation of menstruation for at least 5 years before start of this experiment, were divided into three groups. They received a topical vaginal application daily of 0.1 or 1% (w/w) PM cream or a conjugated equine estrogen (CEE) cream (a mixture of estrone, equilin, 17β-dihydroequilin, 17α-estradiol and 17α-dihydroequilin at 0.625 mg total estrogen/g cream) for 28 days. Estrogenic efficacy was assessed weekly by vaginal cytology assay and vaginal pH measurement, whilst the plasma luteinizing hormone (LH) and sex skin coloration levels were determined at the end of each treatment period to evaluate the systemic side effects. PM significantly increased the proportion of superficial cells in a dose-dependent manner, with a similar efficacy between 1% (w/w) PM and CEE. Together with increased vaginal maturation, PM decreased the vaginal pH to acidic levels, as observed in the CEE group. PM induced no detected systemic side effects, whilst CEE decreased the plasma LH level and increased the reddish color of the sex skin during the posttreatment period. Topical vaginal treatment with PM stimulated the maturation of the vaginal epithelium without causing systemic side effects in postmenopausal monkeys. The implication is that PM could be a safer alternative to treat vaginal atrophy in postmenopausal women. PMID:24748397

  20. Deep brain stimulation: new techniques.

    PubMed

    Hariz, Marwan

    2014-01-01

    The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago. However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects. Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously. Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording. PMID:24262179

  1. Evoked Electromyographically Controlled Electrical Stimulation

    PubMed Central

    Hayashibe, Mitsuhiro

    2016-01-01

    Time-variant muscle responses under electrical stimulation (ES) are often problematic for all the applications of neuroprosthetic muscle control. This situation limits the range of ES usage in relevant areas, mainly due to muscle fatigue and also to changes in stimulation electrode contact conditions, especially in transcutaneous ES. Surface electrodes are still the most widely used in noninvasive applications. Electrical field variations caused by changes in the stimulation contact condition markedly affect the resulting total muscle activation levels. Fatigue phenomena under functional electrical stimulation (FES) are also well known source of time-varying characteristics coming from muscle response under ES. Therefore, it is essential to monitor the actual muscle state and assess the expected muscle response by ES so as to improve the current ES system in favor of adaptive muscle-response-aware FES control. To deal with this issue, we have been studying a novel control technique using evoked electromyography (eEMG) signals to compensate for these muscle time-variances under ES for stable neuroprosthetic muscle control. In this perspective article, I overview the background of this topic and highlight important points to be aware of when using ES to induce the desired muscle activation regardless of the time-variance. I also demonstrate how to deal with the common critical problem of ES to move toward robust neuroprosthetic muscle control with the Evoked Electromyographically Controlled Electrical Stimulation paradigm. PMID:27471448

  2. Laser stimulation for pain research

    NASA Astrophysics Data System (ADS)

    Clark, Stuart; Dickinson, Mark R.; King, Terence A.; Jones, Anthony; Chen, Andrew; Derbyshire, Stuart; Townsend, D. W.; Kinahan, Paul E.; Mintun, M. A.; Nichols, T.

    1996-01-01

    Pain is a serious medical problem; it inflicts huge economic loss and personal suffering. Pain signals are conducted via small, non- and partially myelinated A-delta and C nerve fibers and lasers are particularly well suited to stimulating these fibers. Large myelinated fibers convey touch and vibration information and these fibers are also discharged when contact thermodes and other touch pain stimuli are used and this would give a more muddled signal for functional imaging experiments. The advantages of lasers over conventional methods of pain stimulation are good temporal resolution, no variable parameters are involved such as contact area and they give very reproducible results. Accurate inter-stimulus changes can be achieved by computer control of the laser pulse duration, pulse height and repetition rate and this flexibility enables complex stimulation paradigms to be realized. We present a flexible carbon dioxide laser system designed to generate these stimuli for the study of human cerebral pain responses. We discuss the advantages within research of this system over other methods of pain stimulation such as thermal, electrical and magnetic. The stimulator is used in conjunction with functional magnetic resonance imaging, positron emission tomography and electrophysiological methods of imaging the brain's activity. This combination is a powerful tool for the study of pain-induced activity in different areas of the brain. An accurate understanding of the brain's response to pain will help in research into the areas of rheumatoid arthritis and chronic back pain.

  3. Wireless magnetothermal deep brain stimulation.

    PubMed

    Chen, Ritchie; Romero, Gabriela; Christiansen, Michael G; Mohr, Alan; Anikeeva, Polina

    2015-03-27

    Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors. PMID:25765068

  4. Technology for Peripheral Nerve Stimulation.

    PubMed

    Parker, John L; Cameron, Tracy

    2015-01-01

    Peripheral nerve stimulation (PNS) has been in use for over 50 years to treat patients suffering from chronic pain who have failed conservative treatments. Despite this long history, the devices being used have changed very little. In fact, current PNS technology was developed specifically for spinal cord stimulation. The use of technology developed for other applications in PNS has led to an unnecessary number of device complications and the limited adoption of this promising therapy. The following chapter provides an overview of PNS technology throughout the years, outlining both the benefits and limitations. We will briefly explore the electrophysiology of PNS stimulation, with an emphasis on technology and indication-specific devices. Finally, design and technical requirements of an ideal PNS device will be discussed.

  5. The Electrical Stimulation Modifies the Cerebral Function

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa Lilia; López-Meraz, María Leonor; Cuéllar-Herrera, Manola; Neri-Bazán., Leticia

    2002-08-01

    Electrical stimulation has been used for therapeuthic purposes. In this review, we present the clinical and scientific bases for using electrical stimulation as a treatment for pharmacological refractory epilepsy. We also describe results in receptors of inhibitory neurotransmitters obtained in rat brain with or without epilepsy, undergoing brain stimulation. Brain electrical stimulation may improve our understanding of brain function and neuroplasticity.

  6. Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Tokuda, Takashi; Asano, Ryosuke; Sugitani, Sachie; Taniyama, Mari; Terasawa, Yasuo; Nunoshita, Masahiro; Nakauchi, Kazuaki; Fujikado, Takashi; Tano, Yasuo; Ohta, Jun

    2008-04-01

    The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

  7. Chemosensory stimulation during sleep - Arousal responses to gustatory stimulation.

    PubMed

    Stuck, B A; Moutsis, T T; Bingel, U; Sommer, J U

    2016-05-13

    The processing of nociceptive, visual, vibrotactile, thermal and acoustic stimuli during sleep has been extensively investigated in the past. Recently, interest has focused on the impact of olfactory stimulation on sleep. In contrast to all other sensory systems, olfactory stimulation does not lead to an increased arousal frequency, regardless of hedonicity and concentration. The impact of the second chemosensory system, gustation, on sleep however has not been investigated to date. Twenty-one normosmic and normogeusic volunteers of both genders, aged 19-33 years, participated in the trial. Stimulation was performed with a gustometer using the following aqueous solutions: saccharose 20% (sweet), sodium chloride (NaCl) 7.5% (salty), citrate 5% (sour), and quinine 0.02% (bitter). A tasteless solution was used as negative control. Capsaicin, a strong trigeminal stimulus, served as positive control. Primary outcome was arousal frequency per stimulus in each sleep stage, as assessed with polysomnography. The frequency of arousals decreased in deeper sleep stages (N1: 211 arousals of 333 stimuli=63%, N2: 676/2728=25%, N3: 43/1378=3%, REM: 57/1010=6%). Statistically significant differences in terms of arousal frequency were found in N2 between the negative control and NaCl 100 μl (p<0.001), saccharose 100 μl, citrate 50 μl & 100 μl, and quinine 100 μl (p<0.05). Capsaicin led to complete awakenings in 94% of stimuli (30/32). These results demonstrate that gustatory stimulation during sleep induces arousals depending on stimulus intensity and sleep stage, which is different to olfactory stimulation and may be related to differences in central processing of the two chemosensory systems. PMID:26921652

  8. Infant Stimulation Curriculum. Revised Edition.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Herschel W. Nisonger Center.

    Presented is the Infant Stimulation Curriculum (developed by the Developmentally Delayed Infant Outreach Project) for parents and teachers to use with children who are developmentally between birth and 36 months of age. Published in a card format at a sixth grade readability level, the curriculum includes introductory cards providing information…

  9. Activities to Stimulate Critical Thinking.

    ERIC Educational Resources Information Center

    Haynes, Thomas B.; Schroeder, Connie

    1989-01-01

    Describes sample vocational activities that stimulate critical thinking: (1) setting up an accounting system (business education); (2) developing a marketing plan (marketing education); (3) developing a fertilizer application plan (agricultural education); (4) making the best purchase (home economics); (5) planning a repair/remodeling project…

  10. Aversive Stimulation -- Criteria for Application.

    ERIC Educational Resources Information Center

    O'Donnell, Patrick A.; Ohlson, Glenn A.

    Criteria for applying aversive stimulation with severely handicapped children are examined, and practical and ethical issues are considered. Factors seen to influence punishment outcomes include timing, intensity, and schedule of reinforcement. Suggested is the need for further research on the comparative effectiveness of positive and negative…

  11. Stimulation of phagocytosis by sulforaphane

    SciTech Connect

    Suganuma, Hiroyuki; Fahey, Jed W.; Bryan, Kelley E.; Healy, Zachary R.; Talalay, Paul

    2011-02-04

    Research highlights: {yields} Sulforaphane stimulates the phagocytosis of RAW 264.7 macrophages under conditions of serum deprivation. {yields} This effect does not require Nrf2-dependent induction of phase 2 genes. {yields} Inactivation of macrophage migration inhibitory factor (MIF) by sulforaphane may be involved in stimulation of phagocytosis by sulforaphane. -- Abstract: Sulforaphane, a major isothiocyanate derived from cruciferous vegetables, protects living systems against electrophile toxicity, oxidative stress, inflammation, and radiation. A major protective mechanism is the induction of a network of endogenous cytoprotective (phase 2) genes that are regulated by transcription factor Nrf2. To obtain a more detailed understanding of the anti-inflammatory and immunomodulatory effects of sulforaphane, we evaluated its effect on the phagocytosis activity of RAW 264.7 murine macrophage-like cells by measuring the uptake of 2-{mu}m diameter polystyrene beads. Sulforaphane raised the phagocytosis activity of RAW 264.7 cells but only in the absence or presence of low concentrations (1%) of fetal bovine serum. Higher serum concentrations depressed phagocytosis and abolished its stimulation by sulforaphane. This stimulation did not depend on the induction of Nrf2-regulated genes since it occurred in peritoneal macrophages of nrf2{sup -/-} mice. Moreover, a potent triterpenoid inducer of Nrf2-dependent genes did not stimulate phagocytosis, whereas sulforaphane and another isothiocyanate (benzyl isothiocyanate) had comparable inducer potencies. It has been shown recently that sulforaphane is a potent and direct inactivator of macrophage migration inhibitory factor (MIF), an inflammatory cytokine. Moreover, the addition of recombinant MIF to RAW 264.7 cells attenuated phagocytosis, but sulforaphane-inactivated MIF did not affect phagocytosis. The inactivation of MIF may therefore be involved in the phagocytosis-enhancing activity of sulforaphane.

  12. Somato stimulation and acupuncture therapy.

    PubMed

    Zhao, Jing-Jun; Rong, Pei-Jing; Shi, Li; Ben, Hui; Zhu, Bing

    2016-05-01

    Acupuncture is an oldest somato stimulus medical technique. As the most representative peripheral nerve stimulation therapy, it has a complete system of theory and application and is applicable to a large population. This paper expounds the bionic origins of acupuncture and analyzes the physiological mechanism by which acupuncture works. For living creatures, functionally sound viscera and effective endurance of pain are essential for survival. This paper discusses the way in which acupuncture increases the pain threshold of living creatures and the underlying mechanism from the perspective of bionics. Acupuncture can also help to adjust visceral functions and works most effectively in facilitating the process of digestion and restraining visceral pain. This paper makes an in-depth overview of peripheral nerve stimulation therapy represented by acupuncture. We look forward to the revival of acupuncture, a long-standing somato stimulus medicine, in the modern medical systems.

  13. Multisensory stimulation in stroke rehabilitation.

    PubMed

    Johansson, Barbro Birgitta

    2012-01-01

    The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, and various kinds of music therapy. Non-invasive brain stimulation has showed promising preliminary results in aphasia and neglect. Patient heterogeneity and the interaction of age, gender, genes, and environment are discussed. Randomized controlled longitudinal trials starting earlier post-stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation. It is proposed that we should pay more attention to age, gender, and laterality in clinical studies.

  14. Multisensory Stimulation in Stroke Rehabilitation

    PubMed Central

    Johansson, Barbro Birgitta

    2012-01-01

    The brain has a large capacity for automatic simultaneous processing and integration of sensory information. Combining information from different sensory modalities facilitates our ability to detect, discriminate, and recognize sensory stimuli, and learning is often optimal in a multisensory environment. Currently used multisensory stimulation methods in stroke rehabilitation include motor imagery, action observation, training with a mirror or in a virtual environment, and various kinds of music therapy. Non-invasive brain stimulation has showed promising preliminary results in aphasia and neglect. Patient heterogeneity and the interaction of age, gender, genes, and environment are discussed. Randomized controlled longitudinal trials starting earlier post-stroke are needed. The advance in brain network science and neuroimaging enabling longitudinal studies of structural and functional networks are likely to have an important impact on patient selection for specific interventions in future stroke rehabilitation. It is proposed that we should pay more attention to age, gender, and laterality in clinical studies. PMID:22509159

  15. Stimulated Superconductivity at Strong Coupling

    SciTech Connect

    Bao, Ning; Dong, Xi; Silverstein, Eva; Torroba, Gonzalo; /Stanford U., ITP /Stanford U., Phys. Dept. /SLAC

    2011-08-12

    Stimulating a system with time dependent sources can enhance instabilities, thus increasing the critical temperature at which the system transitions to interesting low-temperature phases such as superconductivity or superfluidity. After reviewing this phenomenon in non-equilibrium BCS theory (and its marginal fermi liquid generalization) we analyze the effect in holographic superconductors. We exhibit a simple regime in which the transition temperature increases parametrically as we increase the frequency of the time-dependent source.

  16. Movement disorders induced by deep brain stimulation.

    PubMed

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-04-01

    Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders. PMID:26806438

  17. Interleukin-6 stimulates defective angiogenesis

    PubMed Central

    Gopinathan, Ganga; Milagre, Carla; Pearce, Oliver M.T.; Reynolds, Louise E.; Hodivala-Dilke, Kairbaan; Leinster, David A.; Zhong, Haihong; Hollingsworth, Robert E.; Thompson, Richard; Whiteford, James R.; Balkwill, Frances

    2015-01-01

    The cytokine interleukin-6 (IL-6) has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here we show that IL-6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL-6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared to VEGF-stimulated vessels. The mechanism of IL-6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as Angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL-6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies there was an association between levels of IL-6mRNA, Jagged1 and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL-6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease and stroke. PMID:26081809

  18. Gastric stimulation for weight loss.

    PubMed

    Mizrahi, Meir; Ben Ya'acov, Ami; Ilan, Yaron

    2012-05-21

    The prevalence of obesity is growing to epidemic proportions, and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss. Behavior and lifestyle therapy are safe treatments for obesity in the short term, but the durability of the weight loss is limited. Although promising obesity drugs are in development, the currently available drugs lack efficacy or have unacceptable side effects. Surgery leads to long-term weight loss, but it is associated with morbidity and mortality. Gastric electrical stimulation (GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders. GES is a promising, minimally invasive, safe, and effective method for treating obesity. External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time. In addition, data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES. This may involve alteration of secretion of hormones associated with hunger or satiety. Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome. Here, we review the current status, potential mechanisms of action, and possible future applications of gastric stimulation for obesity. PMID:22654422

  19. Deep Brain Stimulation Tested for Early Alzheimer's

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160137.html Deep Brain Stimulation Tested for Early Alzheimer's Although treatment seems ... 2016 THURSDAY, July 28, 2016 (HealthDay News) -- Deep brain stimulation appears safe for people with early Alzheimer's ...

  20. Neuromuscular Electrical Stimulation for Skeletal Muscle Function

    PubMed Central

    Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

    2012-01-01

    Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

  1. Electrical stimulation for epilepsy: stimulation of hippocampal foci.

    PubMed

    Velasco, F; Velasco, M; Velasco, A L; Menez, D; Rocha, L

    2001-01-01

    Subacute and chronic continuous electrical stimulation at the epileptic focus in the hippocampus or parahippocampal cortex at 130 Hz, 0.21-1.0 ms, 2.5-3.5 V (about 200-300 microA) induces a decrease in focal EEG epileptic interictal activity and also in the occurrence of clinical seizures. This may represent an alternative for the treatment of temporal lobe seizures originated in bilateral independent temporal lobe foci or occurring in patients where one is uncertain whether memory deficit might result from ablative procedures.

  2. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    Each of the following types of well stimulation techniques are summarized and explained: hydraulic fracturing; thermal; mechanical, jetting, and drainhole drilling; explosive and implosive; and injection methods. Current stimulation techniques, stimulation techniques for geothermal wells, areas of needed investigation, and engineering calculations for various techniques. (MHR)

  3. Modeling and Field Results from Seismic Stimulation

    SciTech Connect

    Majer, E.; Pride, S.; Lo, W.; Daley, T.; Nakagawa, Seiji; Sposito, Garrison; Roberts, P.

    2006-05-30

    Modeling the effect of seismic stimulation employing Maxwell-Boltzmann theory shows that the important component of stimulation is mechanical rather than fluid pressure effects. Modeling using Biot theory (two phases) shows that the pressure effects diffuse too quickly to be of practical significance. Field data from actual stimulation will be shown to compare to theory.

  4. Infant Habituation to Visual and Auditory Stimulation.

    ERIC Educational Resources Information Center

    Dunn, Jane; Haskins, Ron

    A total of 14 infants participated in this study of the recovery of visual orienting by crossmodal stimulation when no new visual information was present. The locus of the crossmodal stimulation (auditory stimulation) was discriminable to the subject. Infants in three age groups were tested on three occasions each separated by 30 days. No…

  5. Vomiting Center reanalyzed: An electrical stimulation study

    NASA Technical Reports Server (NTRS)

    Miller, A. D.; Wilson, V. J.

    1982-01-01

    Electrical stimulation of the brainstem of 15 decerebrate cats produced stimulus-bound vomiting in only 4 animals. Vomiting was reproducible in only one cat. Effective stimulating sites were located in the solitary tract and reticular formation. Restricted localization of a vomiting center, stimulation of which evoked readily reproducible results, could not be obtained.

  6. Brain stimulation and inhibitory control.

    PubMed

    Juan, Chi-Hung; Muggleton, Neil G

    2012-04-01

    Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control. PMID:22494830

  7. Brain stimulation and inhibitory control.

    PubMed

    Juan, Chi-Hung; Muggleton, Neil G

    2012-04-01

    Inhibitory control mechanisms are important in a range of behaviours to prevent execution of motor acts which, having been planned, are no longer necessary or appropriate. Examples of this can be seen in a range of sports, such as cricket and baseball, where the choice between execution and inhibition of a bat swing must be made in a very brief time window. Deficits in inhibitory control have been associated with problems in behavioural regulation in impulsive violence as well as a range of clinical disorders. The roles of various areas, including the frontal eye fields (FEF), the pre-supplementary motor area (pre-SMA) and the inferior frontal gyrus, in inhibitory control have been investigated using an inhibitory control task and both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Typically effects on response inhibition but no effects on response generation have been seen. The contributions of these areas to performance seem to differ with, for example, pre-SMA being involved when the task is relatively novel whereas this is not the case for FEF. The findings from brain stimulation studies offer both insight into which areas are necessary for effective inhibitory control and recent extension of findings for the role of the inferior frontal gyrus illustrate how the specific functions by which these areas contribute may be further clarified. Future work, including making use of the temporal specificity of TMS and combination of TMS/tDCS with other neuroimaging techniques, may further clarify the nature and functions played by the network of areas involved in inhibitory control.

  8. Stimulated Parametric Emission Microscope Systems

    NASA Astrophysics Data System (ADS)

    Itoh, Kazuyoshi; Isobe, Keisuke

    2006-10-01

    We present a novel microscopy technique based on the fourwave mixing (FWM) process that is enhanced by two-photon electronic resonance induced by a pump pulse along with stimulated emission induced by a dump pulse. A Ti:sapphire laser and an optical parametric oscillator are used as light sources for the pump and dump pulses, respectively. We demonstrate that our FWM technique can be used to obtain two-dimensional microscopic images of an unstained leaf of Camellia sinensis and an unlabeled tobacco BY2 Cell.

  9. Stimulated Brillouin Scattering Microscopic Imaging

    PubMed Central

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue. PMID:26691398

  10. Transcranial magnetic stimulation in neurology

    PubMed Central

    Eldaief, Mark C.; Press, Daniel Z.

    2013-01-01

    Summary Transcranial magnetic stimulation (TMS) is a neurophysiologic technique to noninvasively induce a controlled current pulse in a prespecified cortical target. This can be used to transiently disrupt the function of the targeted cortical region and explore causal relations to behavior, assess cortical reactivity, and map out functionally relevant brain regions, for example during presurgical assessments. Particularly when applied repetitively, TMS can modify cortical excitability and the effects can propagate trans-synaptically to interconnected cortical, subcortical, and spinal cord regions. As such, TMS can be used to assess the functional integrity of neural circuits and to modulate brain activity with potential therapeutic intent. PMID:24353923

  11. Multicolor stimulated Raman scattering microscopy

    NASA Astrophysics Data System (ADS)

    Lu, Fa-Ke; Ji, Minbiao; Fu, Dan; Ni, Xiaohui; Freudiger, Christian W.; Holtom, Gary; Xie, X. Sunney

    2012-08-01

    Stimulated Raman scattering (SRS) microscopy has opened up a wide range of biochemical imaging applications by probing a particular Raman-active molecule vibrational mode in the specimen. However, the original implementation with picosecond pulse excitation can only realize rapid chemical mapping with a single Raman band. Here we present a novel SRS microscopic technique using a grating-based pulse shaper for excitation and a grating-based spectrograph for detection to achieve simultaneous multicolor SRS imaging with high sensitivity and high acquisition speeds. In particular, we use a linear combination of the measured CH2 and CH3 stretching signals to map the distributions of protein and lipid contents simultaneously.

  12. Stimulated Brillouin Scattering Microscopic Imaging.

    PubMed

    Ballmann, Charles W; Thompson, Jonathan V; Traverso, Andrew J; Meng, Zhaokai; Scully, Marlan O; Yakovlev, Vladislav V

    2015-01-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  13. Stimulated Brillouin Scattering Microscopic Imaging

    NASA Astrophysics Data System (ADS)

    Ballmann, Charles W.; Thompson, Jonathan V.; Traverso, Andrew J.; Meng, Zhaokai; Scully, Marlan O.; Yakovlev, Vladislav V.

    2015-12-01

    Two-dimensional stimulated Brillouin scattering microscopy is demonstrated for the first time using low power continuous-wave lasers tunable around 780 nm. Spontaneous Brillouin spectroscopy has much potential for probing viscoelastic properties remotely and non-invasively on a microscopic scale. Nonlinear Brillouin scattering spectroscopy and microscopy may provide a way to tremendously accelerate the data aquisition and improve spatial resolution. This general imaging setup can be easily adapted for specific applications in biology and material science. The low power and optical wavelengths in the water transparency window used in this setup provide a powerful bioimaging technique for probing the mechanical properties of hard and soft tissue.

  14. Tissue stimulator enclosure welding fixture

    NASA Technical Reports Server (NTRS)

    Mcclure, S. R.

    1977-01-01

    It was demonstrated that the thickness of the stimulator titanium enclosure is directly related to the battery recharge time cycle. Reduction of the titanium enclosure thickness from approximately 0.37 mm (0.015 inch) to 0.05 mm (0.002 inch) significantly reduced the recharge time cycle and thereby patient inconvenience. However, fabrication of titanium enclosures from the thinner material introduced problems in forming, holding, and welding that required improvement in state of the art shop practices. The procedures that were utilized to resolve these fabrication problems are described.

  15. Pumping effect of stimulated Brillouin scattering on stimulated Raman scattering in water

    NASA Astrophysics Data System (ADS)

    Liu, Dahe; Shi, Jinwei; Ouyang, Min; Chen, Xudong; Liu, Juan; He, Xingdao

    2009-09-01

    It is investigated experimentally that stimulated Raman scattering (SRS) can be enhanced by stimulated Brillouin scattering (SBS). Two physical mechanisms of these phenomena were analyzed. These phenomena show that not only the competition between SBS and SRS exists, the pumping effect of stimulated Brillouin scattering on back-stimulated Raman scattering is also a commonly existing rule regardless of the experimental conditions.

  16. Bubble stimulation efficiency of dinoflagellate bioluminescence.

    PubMed

    Deane, Grant B; Stokes, M Dale; Latz, Michael I

    2016-02-01

    Dinoflagellate bioluminescence, a common source of bioluminescence in coastal waters, is stimulated by flow agitation. Although bubbles are anecdotally known to be stimulatory, the process has never been experimentally investigated. This study quantified the flash response of the bioluminescent dinoflagellate Lingulodinium polyedrum to stimulation by bubbles rising through still seawater. Cells were stimulated by isolated bubbles of 0.3-3 mm radii rising at their terminal velocity, and also by bubble clouds containing bubbles of 0.06-10 mm radii for different air flow rates. Stimulation efficiency, the proportion of cells producing a flash within the volume of water swept out by a rising bubble, decreased with decreasing bubble radius for radii less than approximately 1 mm. Bubbles smaller than a critical radius in the range 0.275-0.325 mm did not stimulate a flash response. The fraction of cells stimulated by bubble clouds was proportional to the volume of air in the bubble cloud, with lower stimulation levels observed for clouds with smaller bubbles. An empirical model for bubble cloud stimulation based on the isolated bubble observations successfully reproduced the observed stimulation by bubble clouds for low air flow rates. High air flow rates stimulated more light emission than expected, presumably because of additional fluid shear stress associated with collective buoyancy effects generated by the high air fraction bubble cloud. These results are relevant to bioluminescence stimulation by bubbles in two-phase flows, such as in ship wakes, breaking waves, and sparged bioreactors.

  17. Infrared neural stimulation in the cochlea

    PubMed Central

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2014-01-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed. PMID:25075260

  18. Infrared neural stimulation in the cochlea.

    PubMed

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2013-03-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed. PMID:25075260

  19. Deep Brain Stimulation for Obesity

    PubMed Central

    Sussman, Eric S; Zhang, Michael; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-01-01

    Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer’s disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain. PMID:26180683

  20. Braille line using electrical stimulation

    NASA Astrophysics Data System (ADS)

    Puertas, A.; Purés, P.; Echenique, A. M.; Ensinck, J. P. Graffigna y. G.

    2007-11-01

    Conceived within the field of Rehabilitation Technologies for visually impaired persons, the present work aims at enabling the blind user to read written material by means of a tactile display. Once he is familiarized to operate this system, the user will be able to achieve greater performance in study, academic and job activities, thus achieving a rapid and easier social inclusion. The devise accepts any kind of text that is computer-loadable (documents, books, Internet information, and the like) which, through digital means, can be read as Braille text on the pad. This tactile display is composed of an electrodes platform that simulate, through stimulation the writing/reading Braille characters. In order to perceive said characters in similar way to the tactile feeling from paper material, the skin receptor of fingers are stimulated electrically so as to simulate the same pressure and depressions as those of the paper-based counterpart information. Once designed and developed, the display was tested with blind subjects, with relatively satisfactory results. As a continuing project, this prototype is currently being improved as regards.

  1. Optogenetic stimulation of the auditory pathway

    PubMed Central

    Hernandez, Victor H.; Gehrt, Anna; Reuter, Kirsten; Jing, Zhizi; Jeschke, Marcus; Mendoza Schulz, Alejandro; Hoch, Gerhard; Bartels, Matthias; Vogt, Gerhard; Garnham, Carolyn W.; Yawo, Hiromu; Fukazawa, Yugo; Augustine, George J.; Bamberg, Ernst; Kügler, Sebastian; Salditt, Tim; de Hoz, Livia; Strenzke, Nicola; Moser, Tobias

    2014-01-01

    Auditory prostheses can partially restore speech comprehension when hearing fails. Sound coding with current prostheses is based on electrical stimulation of auditory neurons and has limited frequency resolution due to broad current spread within the cochlea. In contrast, optical stimulation can be spatially confined, which may improve frequency resolution. Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). Optogenetic stimulation of spiral ganglion neurons (SGNs) activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses. Furthermore, optogenetic stimulation of SGNs restored auditory activity in deaf mice. Approximation of the spatial spread of cochlear excitation by recording local field potentials (LFPs) in the inferior colliculus in response to suprathreshold optical, acoustic, and electrical stimuli indicated that optogenetic stimulation achieves better frequency resolution than monopolar electrical stimulation. Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. Our study demonstrates a strategy for optogenetic stimulation of the auditory pathway in rodents and lays the groundwork for future applications of cochlear optogenetics in auditory research and prosthetics. PMID:24509078

  2. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  3. Vestibular stimulation by magnetic fields

    PubMed Central

    Ward, Bryan K.; Roberts, Dale C.; Della Santina, Charles C.; Carey, John P.; Zee, David S.

    2015-01-01

    Individuals working next to strong static magnetic fields occasionally report disorientation and vertigo. With the increasing strength of magnetic fields used for magnetic resonance imaging (MRI) studies, these reports have become more common. It was recently learned that humans, mice and zebrafish all demonstrate behaviors consistent with constant peripheral vestibular stimulation while inside a strong, static magnetic field. The proposed mechanism for this effect involves a Lorentz force resulting from the interaction of a strong static magnetic field with naturally occurring ionic currents flowing through the inner ear endolymph into vestibular hair cells. The resulting force within the endolymph is strong enough to displace the lateral semicircular canal cupula, inducing vertigo and the horizontal nystagmus seen in normal mice and in humans. This review explores the evidence for interactions of magnetic fields with the vestibular system. PMID:25735662

  4. Electrode array for neural stimulation

    DOEpatents

    Wessendorf, Kurt O.; Okandan, Murat; Stein, David J.; Yang, Pin; Cesarano, III, Joseph; Dellinger, Jennifer

    2011-08-16

    An electrode array for neural stimulation is disclosed which has particular applications for use in a retinal prosthesis. The electrode array can be formed as a hermetically-sealed two-part ceramic package which includes an electronic circuit such as a demultiplexer circuit encapsulated therein. A relatively large number (up to 1000 or more) of individually-addressable electrodes are provided on a curved surface of a ceramic base portion the electrode array, while a much smaller number of electrical connections are provided on a ceramic lid of the electrode array. The base and lid can be attached using a metal-to-metal seal formed by laser brazing. Electrical connections to the electrode array can be provided by a flexible ribbon cable which can also be used to secure the electrode array in place.

  5. Acupuncture stimulation and neuroendocrine regulation.

    PubMed

    Yu, Jung-Sheng; Zeng, Bai-Yun; Hsieh, Ching-Liang

    2013-01-01

    Acupuncture has been used to treat different conditions for at least 3000 years in China and has gained increasing acceptance worldwide. The acupuncture needle inserted into the muscle layer at the acupoint produces the so-called obtaining qi sensation that causes the excitation of A-δ and C-fibers of the muscle tissue, resulting in afferent signals. The afferent signals pass through the dorsal horn cells of the spinal cord ascending to the brain, such as the hypothalamus, enhancing the release of neuropeptides and hormones, and these afferent signals in the spinal segment may innervate the visceral organ, inducing effect on visceral function. Here, we reviewed the effect of acupuncture stimulation on neuropeptides and hormones, including β-endorphin, serotonin, oxytocin, adrenocorticotropic hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, cholecystokinin, and acetylcholine, as well as insulin sensitivity, immunomodulation (anti-inflammation), and autonomic nerve activity. PMID:24215920

  6. [Use of erythropoiesis stimulating agents].

    PubMed

    Lapierre, A; Souquet, P-J

    2014-02-01

    Anemia is fairly common in lung neoplasms and adequate management can influence both the prognosis and the quality of life of patients. Anemia can stem from diverse mechanisms, and its management must include the search for correctable causes (iron deficiency, inflammation, disease- or treatment-related), and their subsequent treatment. Use of erythropoiesis stimulating agents, namely recombinant erythropoietin, results in hemoglobin increase, fewer blood transfusions, and better quality of life. However, there is also a significant increase in thromboembolic risk associated with this treatment, and their effect on overall survival is still debated. Thus, their use must be restricted to patients treated with palliative intent, receiving chemotherapy but no radiotherapy, with a baseline hemoglobin level under 100 g/L, and target hemoglobin level must not exceed 120 g/L.

  7. Mimicking muscle activity with electrical stimulation

    NASA Astrophysics Data System (ADS)

    Johnson, Lise A.; Fuglevand, Andrew J.

    2011-02-01

    Functional electrical stimulation is a rehabilitation technology that can restore some degree of motor function in individuals who have sustained a spinal cord injury or stroke. One way to identify the spatio-temporal patterns of muscle stimulation needed to elicit complex upper limb movements is to use electromyographic (EMG) activity recorded from able-bodied subjects as a template for electrical stimulation. However, this requires a transfer function to convert the recorded (or predicted) EMG signals into an appropriate pattern of electrical stimulation. Here we develop a generalized transfer function that maps EMG activity into a stimulation pattern that modulates muscle output by varying both the pulse frequency and the pulse amplitude. We show that the stimulation patterns produced by this transfer function mimic the active state measured by EMG insofar as they reproduce with good fidelity the complex patterns of joint torque and joint displacement.

  8. Increased skin temperature during transcutaneous electrical stimulation.

    PubMed

    Abram, S E; Asiddao, C B; Reynolds, A C

    1980-01-01

    Conflicting reports have appeared in the literature concerning the effects of transcutaneous electrical nerve stimulation on skin temperature. This report studied 33 patients with chronic pain involving one extremity (13 upper, 20 lower) to determine whether changes in sympathetic tone, as reflected in skin temperature, occurred in response to electrical stimulation of painful areas. Stimulation was carried out for 20 to 45 minutes. Skin temperatures were measured from the thumbs or great toes of stimulated and contralateral extremities before and during stimulation. Skin temperature rose 2.5 +/- 0.7 (mean +/- SEM) in both the ipsilateral and contralateral extremity in patients who experienced relief of pain during stimulation. There was no significant change in skin temperature in patients who experienced no relief.

  9. Analysis of Facial Expression by Taste Stimulation

    NASA Astrophysics Data System (ADS)

    Tobitani, Kensuke; Kato, Kunihito; Yamamoto, Kazuhiko

    In this study, we focused on the basic taste stimulation for the analysis of real facial expressions. We considered that the expressions caused by taste stimulation were unaffected by individuality or emotion, that is, such expressions were involuntary. We analyzed the movement of facial muscles by taste stimulation and compared real expressions with artificial expressions. From the result, we identified an obvious difference between real and artificial expressions. Thus, our method would be a new approach for facial expression recognition.

  10. A Microcomputer-Based Neurophysiological Stimulator

    PubMed Central

    Halter, John

    1979-01-01

    A neurophysiological stimulator is presented which utilizes TTL hardware controlled by a microcomputer. Up to four channels of stimulation are provided, each of which consists of a TTL-Based Pulse Generator. Operating parameters are entered into the stimulator via a front panel in a format familiar to the clinician. Operating parameters may be investigated and modified at any time by another computer, thereby enabling the implementation of more complex clinical procedures. ImagesFigure 1Figure 4

  11. Geothermal Reservoir Well Stimulation Program: technology transfer

    SciTech Connect

    Not Available

    1980-05-01

    A literature search on reservoir and/or well stimulation techniques suitable for application in geothermal fields is presented. The literature on stimulation techniques in oil and gas field applications was also searched and evaluated as to its relevancy to geothermal operations. The equivalent low-temperature work documented in the open literature is cited, and an attempt is made to evaluate the relevance of this information as far as high-temperature stimulation work is concerned. Clays play an important role in any stimulation work. Therefore, special emphasis has been placed on clay behavior anticipated in geothermal operations. (MHR)

  12. Transcranial Direct Current Stimulation in Stroke Recovery

    PubMed Central

    Schlaug, Gottfried; Renga, Vijay; Nair, Dinesh

    2009-01-01

    TDCS - Transcranial Direct Current Stimulation - is an emerging technique of non-invasive brain stimulation that has been found useful in examining cortical function in normal subjects and in facilitating treatments of various neurological disorders. A better understanding of adaptive as well as maladaptive post-stroke neuroplasticity and its modulation through non-invasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We will review TDCS’s role as a facilitator of stroke recovery, the different modes of transcranial direct current stimulation, and the potential mechanisms underlying the neural effects of TDCS. PMID:19064743

  13. Ovarian stimulation in patients with breast cancer.

    PubMed

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  14. [Deep brain stimulation in schizophrenia].

    PubMed

    Kuhn, J; Bodatsch, M; Sturm, V; Lenartz, D; Klosterkötter, J; Uhlhaas, P J; Winter, C; Gründler, T O J

    2011-11-01

    Deep brain stimulation (DBS) has successfully advanced our treatment options for putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation, more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially, schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here, we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronisation. In conclusion, the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might hinder the use of DBS for schizophrenia at this point in time.

  15. Transcranial Magnetic Stimulation for Schizophrenia.

    PubMed

    Dougall, Nadine; Maayan, Nicola; Soares-Weiser, Karla; McDermott, Lisa M; McIntosh, Andrew

    2015-11-01

    People with schizophrenia typically experience auditory hallucinations or delusions during acute episodes. Although effective drug treatments are available, many have intractable symptoms that do not recover between acute episodes. One proposed alternative to drug treatments is transcranial magnetic stimulation (TMS). To date, many research trials to assess effectiveness of TMS for people with symptoms of schizophrenia have been conducted worldwide. However, there is a lack of consensus on whether TMS should be recommended to be adopted in routine clinical practice. We conducted a systematic review of the literature for all relevant randomized controlled trials (RCTs) comparing TMS with sham or standard treatment. Forty-one trials (1473 participants) survived eligibility criteria and had extractable data. We found significant differences in favor of temporoparietal TMS compared with sham TMS for global state (7 RCTs, n = 224, MD: -0.5, 95% CI: -0.76 to -0.23) and for positive symptoms measured on the Positive and Negative Syndrome Scale (5 RCTs, n = 127, MD: -6.09, 95% CI: -10.95 to -1.22). However, we also found that the quality of trial reporting was frequently suboptimal and the risks of bias were strong or unascertainable for many trial aspects; this led to many results being graded as very low-quality evidence. On that basis, we were unable to definitively support or refute the routine use of TMS in clinical practice. Future definitive trials of TMS with rigorous processes and high-quality reporting are needed.

  16. Digital electronic bone growth stimulator

    DOEpatents

    Kronberg, J.W.

    1993-01-01

    The present invention relates to the electrical treatment of biological tissue. In particular, the present invention discloses a device that produces discrete electrical pulse trains for treating osteoporosis and accelerating bone growth. According to its major aspects and broadly stated, the present invention consists of an electrical circuit configuration capable of generating Bassett-type waveforms shown with alternative signals provide for the treatment of either fractured bones or osteoporosis. The signal generator comprises a quartz clock, an oscillator circuit, a binary divider chain, and a plurality of simple, digital logic gates. Signals are delivered efficiently, with little or no distortion, and uniformly distributed throughout the area of injury. Perferably, power is furnished by widely available and inexpensive radio batteries, needing replacement only once in several days. The present invention can be affixed to a medical cast without a great increase in either weight or bulk. Also, the disclosed stimulator can be used to treat osteoporosis or to strengthen a healing bone after the cast has been removed by attaching the device to the patient`s skin or clothing.

  17. Hyperthermia Stimulates HIV-1 Replication

    PubMed Central

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42–45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38–40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity. PMID:22807676

  18. Three-dimensional visual stimulator

    NASA Astrophysics Data System (ADS)

    Takeda, Tsunehiro; Fukui, Yukio; Hashimoto, Keizo; Hiruma, Nobuyuki

    1995-02-01

    We describe a newly developed three-dimensional visual stimulator (TVS) that can change independently the directions, distances, sizes, luminance, and varieties of two sets of targets for both eyes. It consists of liquid crystal projectors (LCP's) that generate the flexible images of targets, Badal otometers that change target distances without changing the visual angles, and relay-lens systems that change target directions. A special control program is developed for real-time control of six motors and two LCP's in the TVS together with a three-dimensional optometer III that simultaneously measures eye movement, accommodation, pupil diameter, and head movement. distance, 0 to -20 D; direction, 16 horizontally and 15 vertically; size, 0-2 deg visual angle; and luminance, 10-2-10 2 cd/m2. The target images are refreshed at 60 Hz and speeds with which the target makes a smooth change (ramp stimuli) are size, 10 deg/s. A simple application demonstrates the performance.

  19. Electrocutaneous stimulation system for Braille reading.

    PubMed

    Echenique, Ana Maria; Graffigna, Juan Pablo; Mut, Vicente

    2010-01-01

    This work is an assistive technology for people with visual disabilities and aims to facilitate access to written information in order to achieve better social inclusion and integration into work and educational activities. Two methods of electrical stimulation (by current and voltage) of the mechanoreceptors was tested to obtain tactile sensations on the fingertip. Current and voltage stimulation were tested in a Braille cell and line prototype, respectively. These prototypes are evaluated in 33 blind and visually impaired subjects. The result of experimentation with both methods showed that electrical stimulation causes sensations of touch defined in the fingertip. Better results in the Braille characters reading were obtained with current stimulation (85% accuracy). However this form of stimulation causes uncomfortable sensations. The latter feeling was minimized with the method of voltage stimulation, but with low efficiency (50% accuracy) in terms of identification of the characters. We concluded that electrical stimulation is a promising method for the development of a simple and unexpensive Braille reading system for blind people. We observed that voltage stimulation is preferred by the users. However, more experimental tests must be carry out in order to find the optimum values of the stimulus parameters and increase the accuracy the Braille characters reading.

  20. Stimulated Cherenkov emission in gas dynamics

    SciTech Connect

    Kuzelev, M. V. Rukhadze, A. A.

    2008-11-15

    A linear theory is developed for stimulated Cherenkov emission from planar and cylindrical gas flows in gaseous environments. An analogy is demonstrated between Cherenkov emission in gas dynamics and stimulated Cherenkov electromagnetic emission from a charged particle beam in a medium.

  1. Passive Auditory Stimulation Improves Vision in Hemianopia

    PubMed Central

    Lewald, Jörg; Tegenthoff, Martin; Peters, Sören; Hausmann, Markus

    2012-01-01

    Techniques employed in rehabilitation of visual field disorders such as hemianopia are usually based on either visual or audio-visual stimulation and patients have to perform a training task. Here we present results from a completely different, novel approach that was based on passive unimodal auditory stimulation. Ten patients with either left or right-sided pure hemianopia (without neglect) received one hour of unilateral passive auditory stimulation on either their anopic or their intact side by application of repetitive trains of sound pulses emitted simultaneously via two loudspeakers. Immediately before and after passive auditory stimulation as well as after a period of recovery, patients completed a simple visual task requiring detection of light flashes presented along the horizontal plane in total darkness. The results showed that one-time passive auditory stimulation on the side of the blind, but not of the intact, hemifield of patients with hemianopia induced an improvement in visual detections by almost 100% within 30 min after passive auditory stimulation. This enhancement in performance was reversible and was reduced to baseline 1.5 h later. A non-significant trend of a shift of the visual field border toward the blind hemifield was obtained after passive auditory stimulation. These results are compatible with the view that passive auditory stimulation elicited some activation of the residual visual pathways, which are known to be multisensory and may also be sensitive to unimodal auditory stimuli as were used here. Trial Registration DRKS00003577 PMID:22666311

  2. [MRI compatibility of deep brain stimulator].

    PubMed

    Zhang, Yujing

    2013-07-01

    Deep brain stimulation (DBS) therapy develops rapidly in clinical application. The structures of deep brain stimulator and magnetic resonance imaging (MRI) equipment are introduced, the interactions are analyzed, and the two compatible problems of radio frequency (RF) heating and imaging artifact are summarized in this paper.

  3. Stimulation Activities: Age Birth to Five Years.

    ERIC Educational Resources Information Center

    Bloomgarden, Dave

    This handbook provides a collection of stimulation activities that encourage a child's physical and mental growth from birth to five years of age. Emphasis is placed on making stimulation aids that are inexpensive or can be made from scrap materials. Advice is given about ways to carry out designated activities. All activities have been tried and…

  4. Pseudomonas putida Stimulates Primordia on Agaricus bitorquis.

    PubMed

    Colauto, Nelson B; Fermor, Terry R; Eira, Augusto F; Linde, Giani A

    2016-04-01

    Casing layer is one step of Agaricus bisporus cultivation where there is a competitive environment with a high number of microorganisms and diversity interacting with mycelia. It is suggested that a minimal community of these microorganisms would be necessary to stimulate fructification. However, A. bisporus is not able to produce primordia in sterile casing layers or Petri dishes. Thus, the objective of this study was to characterize bacterial microbiota of casing layers from A. bisporus cultivation, isolate, identify and characterize the bacteria responsible for the stimulation of primordium and their action mechanism using Agaricus bitorquis as a primordium stimulation model. Bacterial and Pseudomonas spp. communities of different casing layers of A. bisporus cultivation were collected and quantified. It was concluded that Pseudomonas spp. corresponds to 75-85% of bacterial population of the casing layers in A. bisporus cultivation and among those 12% are Pseudomonas putida. Four biochemical assays were used to identify P. putida. In vitro primordium stimulation of living P. putida and non-living bacterial suspensions, after chemical or physical treatments, was tested using A. bitorquis as a primordium stimulation model. Primordium stimulation assay was registered by photographs, and micrographs of vertical cut of primordium were registered by scanning electron microscope. Interaction of living P. putida with A. bitorquis mycelia is capable of stimulating primordial instead of non-living bacterial suspensions. Stimulation of A. bitorquis primordia does not imply or is related to mycelial growth inhibition, but a hierarchical relation of primordium succession and development is suggested. PMID:26742772

  5. Ultraviolet Light: Some Considerations for Vision Stimulation.

    ERIC Educational Resources Information Center

    Knowlton, Marie

    1986-01-01

    The article examines evidence of visual impairment caused by excessive amounts of ultraviolet (UV) light. Among considerations when using a source of UV light for vision stimulation are the position of the child and teacher, use of window glass filters or protective glasses, and careful recordkeeping of all UV stimulation. (Author/JW)[

  6. Neurologic Complications of Psychomotor Stimulant Abuse.

    PubMed

    Sanchez-Ramos, Juan

    2015-01-01

    Psychomotor stimulants are drugs that act on the central nervous system (CNS) to increase alertness, elevate mood, and produce a sense of well-being. These drugs also decrease appetite and the need for sleep. Stimulants can enhance stamina and improve performance in tasks that have been impaired by fatigue or boredom. Approved therapeutic applications of stimulants include attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. These agents also possess potent reinforcing properties that can result in excessive self-administration and abuse. Chronic use is associated with adverse effects including psychosis, seizures, and cerebrovascular accidents, though these complications usually occur in individuals with preexisting risk factors. This chapter reviews the adverse neurologic consequences of chronic psychomotor stimulant use and abuse, with a focus on two prototypical stimulants methamphetamine and cocaine. PMID:26070756

  7. Relief of pain by transcutaneous stimulation.

    PubMed

    Loeser, J D; Black, R G; Christman, A

    1975-03-01

    A series of 198 patients with chronic pain of diverse etiology was carefully analyzed for epidemiologic and descriptive factors which might influence the response to transcutaneous stimulation. The overall series included 12 1/2% with long-term success, and 68% with partial or short-term relief. There were no consistent specific diagnoses, or epidemiologic or descriptive factors that made good results from stimulation predictable. Stimulation of the painful area itself was not always necessary for pain relief. Favorable responses to transcutaneous stimulation were usually correlated with the continued existence of significant sensory input from the painful region. The authors conclude that transcutaneous stimulation is a valuable therapeutic modality for some patients with chronic pain.

  8. Optical nerve stimulation for a vestibular prosthesis

    NASA Astrophysics Data System (ADS)

    Harris, David M.; Bierer, Steven M.; Wells, Jonathon D.; Phillips, James O.

    2009-02-01

    Infrared Nerve Stimulation (INS) offers several advantages over electrical stimulation, including more precise spatial selectivity and improved surgical access. In this study, INS and electrical stimulation were compared in their ability to activate the vestibular branch of the VIIIth nerve, as a potential way to treat balance disorders. The superior and lateral canals of the vestibular system of Guinea pigs were identified and approached with the aid of precise 3-D reconstructions. A monopolar platinum stimulating electrode was positioned near the ampullae of the canals, and biphasic current pulses were used to stimulate vestibular evoked potentials and eye movements. Thresholds and input/output functions were measured for various stimulus conditions. A short pulsed diode laser (Capella, Lockheed Martin-Aculight, Inc., Bothell WA) was placed in the same anatomical position and various stimulus conditions were evaluated in their ability to evoke similar potentials and eye movements.

  9. Advances in functional electrical stimulation (FES).

    PubMed

    Popović, Dejan B

    2014-12-01

    This review discusses the advancements that are needed to enhance the effects of electrical stimulation for restoring or assisting movement in humans with an injury/disease of the central nervous system. A complex model of the effects of electrical stimulation of peripheral systems is presented. The model indicates that both the motor and sensory systems are activated by electrical stimulation. We propose that a hierarchical hybrid controller may be suitable for functional electrical stimulation (FES) because this type of controller acts as a structural mimetic of its biological counterpart. Specific attention is given to the neural systems at the periphery with respect to the required electrodes and stimulators. Furthermore, we note that FES with surface electrodes is preferred for the therapy, although there is a definite advantage associated with implantable technology for life-long use. The last section of the review discusses the potential need to combine FES and robotic systems to provide assistance in some cases. PMID:25287528

  10. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation

    PubMed Central

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-01-01

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes. PMID:26193273

  11. Stimulating the Comfort of Textile Electrodes in Wearable Neuromuscular Electrical Stimulation.

    PubMed

    Zhou, Hui; Lu, Yi; Chen, Wanzhen; Wu, Zhen; Zou, Haiqing; Krundel, Ludovic; Li, Guanglin

    2015-07-16

    Textile electrodes are becoming an attractive means in the facilitation of surface electrical stimulation. However, the stimulation comfort of textile electrodes and the mechanism behind stimulation discomfort is still unknown. In this study, a textile stimulation electrode was developed using conductive fabrics and then its impedance spectroscopy, stimulation thresholds, and stimulation comfort were quantitatively assessed and compared with those of a wet textile electrode and a hydrogel electrode on healthy subjects. The equivalent circuit models and the finite element models of different types of electrode were built based on the measured impedance data of the electrodes to reveal the possible mechanism of electrical stimulation pain. Our results showed that the wet textile electrode could achieve similar stimulation performance as the hydrogel electrode in motor threshold and stimulation comfort. However, the dry textile electrode was found to have very low pain threshold and induced obvious cutaneous painful sensations during stimulation, in comparison to the wet and hydrogel electrodes. Indeed, the finite element modeling results showed that the activation function along the z direction at the depth of dermis epidermis junction of the dry textile electrode was significantly larger than that of the wet and hydrogel electrodes, thus resulting in stronger activation of pain sensing fibers. Future work will be done to make textile electrodes have similar stimulation performance and comfort as hydrogel electrodes.

  12. Electrical stimulation to accelerate wound healing

    PubMed Central

    Thakral, Gaurav; LaFontaine, Javier; Najafi, Bijan; Talal, Talal K.; Kim, Paul; Lavery, Lawrence A.

    2013-01-01

    Background There are several applications of electrical stimulation described in medical literature to accelerate wound healing and improve cutaneous perfusion. This is a simple technique that could be incorporated as an adjunctive therapy in plastic surgery. The objective of this review was to evaluate the results of randomized clinical trials that use electrical stimulation for wound healing. Method We identified 21 randomized clinical trials that used electrical stimulation for wound healing. We did not include five studies with treatment groups with less than eight subjects. Results Electrical stimulation was associated with faster wound area reduction or a higher proportion of wounds that healed in 14 out of 16 wound randomized clinical trials. The type of electrical stimulation, waveform, and duration of therapy vary in the literature. Conclusion Electrical stimulation has been shown to accelerate wound healing and increase cutaneous perfusion in human studies. Electrical stimulation is an adjunctive therapy that is underutilized in plastic surgery and could improve flap and graft survival, accelerate postoperative recovery, and decrease necrosis following foot reconstruction. PMID:24049559

  13. A fully implantable rodent neural stimulator

    NASA Astrophysics Data System (ADS)

    Perry, D. W. J.; Grayden, D. B.; Shepherd, R. K.; Fallon, J. B.

    2012-02-01

    The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

  14. Computational modeling of epidural cortical stimulation

    NASA Astrophysics Data System (ADS)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2008-12-01

    Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

  15. Numerical dosimetry of transcranial magnetic stimulation coils

    NASA Astrophysics Data System (ADS)

    Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique capable of stimulating neurons by means of electromagnetic induction. TMS can be used to map brain function and shows promise for the diagnosis and treatment of neurological and psychiatric disorders. Calculation of fields induced in the brain are necessary to accurately identify stimulated neural tissue during TMS. This allows the development of novel TMS coil designs capable of stimulating deeper brain regions and increasing the localization of stimulation that can be achieved. We have performed numerical calculations of magnetic and electric field with high-resolution anatomically realistic human head models to find these stimulated brain regions for a variety of proposed TMS coil designs. The realistic head models contain heterogeneous tissue structures and electrical conductivities, yielding superior results to those obtained from the simplified homogeneous head models that are commonly employed. The attenuation of electric field as a function of depth in the brain and the localization of stimulating field have been methodically investigated. In addition to providing a quantitative comparison of different TMS coil designs the variation of induced field between subjects has been investigated. We also show the differences in induced fields between adult, adolescent and child head models to preemptively identify potential safety issues in the application of pediatric TMS.

  16. Controlling illegal stimulants: a regulated market model

    PubMed Central

    Haden, Mark

    2008-01-01

    Prohibition of illegal drugs is a failed social policy and new models of regulation of these substances are needed. This paper explores a proposal for a post-prohibition, public health based model for the regulation of the most problematic drugs, the smokable and injectable stimulants. The literature on stimulant maintenance is explored. Seven foundational principles are suggested that could support this regulatory model of drug control that would reduce both health and social problems related to illegal stimulants. Some details of this model are examined and the paper concludes that drug policies need to be subject to research and based on evidence. PMID:18215317

  17. Electrical Cerebral Stimulation Modifies Inhibitory Systems

    NASA Astrophysics Data System (ADS)

    Cuéllar-Herrera, M.; Rocha, L.

    2003-09-01

    Electrical stimulation of the nervous tissue has been proposed as a method to treat some neurological disorders, such as epilepsy. Epileptic seizures result from excessive, synchronous, abnormal firing patterns of neurons that are located predominantly in the cerebral cortex. Many people with epilepsy continue presenting seizures even though they are under regimens of antiepileptic medications. An alternative therapy for treatment resistant epilepsy is cerebral electrical stimulation. The present study is focused to review the effects of different types of electrical stimulation and specifically changes in amino acids.

  18. Stimulation Technologies for Deep Well Completions

    SciTech Connect

    Stephen Wolhart

    2005-06-30

    The Department of Energy (DOE) is sponsoring the Deep Trek Program targeted at improving the economics of drilling and completing deep gas wells. Under the DOE program, Pinnacle Technologies conducted a study to evaluate the stimulation of deep wells. The objective of the project was to review U.S. deep well drilling and stimulation activity, review rock mechanics and fracture growth in deep, high-pressure/temperature wells and evaluate stimulation technology in several key deep plays. This report documents results from this project.

  19. Towards a Switched-Capacitor based Stimulator for efficient deep-brain stimulation.

    PubMed

    Vidal, Jose; Ghovanloo, Maysam

    2010-01-01

    We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

  20. Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

    PubMed Central

    Vidal, Jose; Ghovanloo, Maysam

    2013-01-01

    We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

  1. Deep Brain Stimulation using Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Jiles, David; Williams, Paul; Crowther, Lawrence; Iowa State University Team; Wolfson CentreMagnetics Team

    2011-03-01

    New applications for transcranial magnetic stimulation are developing rapidly for both diagnostic and therapeutic purposes. Therefore so is the demand for improved performance, particularly in terms of their ability to stimulate deeper regions of the brain and to do so selectively. The coil designs that are used presently are limited in their ability to stimulate the brain at depth and with high spatial focality. Consequently, any improvement in coil performance would have a significant impact in extending the usefulness of TMS in both clinical applications and academic research studies. New and improved coil designs have then been developed, modeled and tested as a result of this work. A large magnetizing coil, 300mm in diameter and compatible with a commercial TMS system has been constructed to determine its feasibility for use as a deep brain stimulator. The results of this work have suggested directions that could be pursued in order to further improve the coil designs.

  2. Stimulation Technologies for Deep Well Completions

    SciTech Connect

    2003-09-30

    The Department of Energy (DOE) is sponsoring the Deep Trek Program targeted at improving the economics of drilling and completing deep gas wells. Under the DOE program, Pinnacle Technologies is conducting a study to evaluate the stimulation of deep wells. The objective of the project is to assess U.S. deep well drilling & stimulation activity, review rock mechanics & fracture growth in deep, high pressure/temperature wells and evaluate stimulation technology in several key deep plays. An assessment of historical deep gas well drilling activity and forecast of future trends was completed during the first six months of the project; this segment of the project was covered in Technical Project Report No. 1. The second progress report covers the next six months of the project during which efforts were primarily split between summarizing rock mechanics and fracture growth in deep reservoirs and contacting operators about case studies of deep gas well stimulation.

  3. Mild stimulation in in vitro fertilization.

    PubMed

    Macklon, N S; Fauser, B C J M

    2003-11-01

    Current approaches to ovarian stimulation for in vitro fertilization (IVF) are aimed at optimizing the number of oocytes retrieved in a treatment cycle. This approach is not without risks. Moreover, as the true costs of multiple pregnancy become clearer, the need to produce multiple embryos for transfer is increasingly questioned. Increasing knowledge of the physiological mechanisms involved in follicular development and dominance has led to new strategies in ovarian stimulation for IVF. The clinical availability of GnRH antagonists allows the normal cycle to be harnessed and manipulated by mild interventions to produce sufficient oocytes for successful IVF treatment. Recent evidence suggests that oocyte quality after mild stimulation may be superior to that after conventional stimulation regimens.

  4. Follicle-stimulating hormone (FSH) blood test

    MedlinePlus

    ... the test done on certain days of your menstrual cycle. ... In women, FSH helps manage the menstrual cycle and stimulates the ovaries to produce eggs. The test is used to help diagnose or evaluate: Menopause Women who have polycystic ovary ...

  5. Implantable neurotechnologies: electrical stimulation and applications.

    PubMed

    Nag, Sudip; Thakor, Nitish V

    2016-01-01

    Neural stimulation using injected electrical charge is widely used both in functional therapies and as an experimental tool for neuroscience applications. Electrical pulses can induce excitation of targeted neural pathways that aid in the treatment of neural disorders or dysfunction of the central and peripheral nervous system. In this review, we summarize the recent trends in the field of electrical stimulation for therapeutic interventions of nervous system disorders, such as for the restoration of brain, eye, ear, spinal cord, nerve and muscle function. Neural prosthetic applications are discussed, and functional electrical stimulation parameters for treating such disorders are reviewed. Important considerations for implantable packaging and enhancing device reliability are also discussed. Neural stimulators are expected to play a profound role in implantable neural devices that treat disorders and help restore functions in injured or disabled nervous system. PMID:26753775

  6. Tactile stimulation lowers stress in fish.

    PubMed

    Soares, Marta C; Oliveira, Rui F; Ros, Albert F H; Grutter, Alexandra S; Bshary, Redouan

    2011-01-01

    In humans, physical stimulation, such as massage therapy, reduces stress and has demonstrable health benefits. Grooming in primates may have similar effects but it remains unclear whether the positive effects are due to physical contact or to its social value. Here we show that physical stimulation reduces stress in a coral reef fish, the surgeonfish Ctenochaetus striatus. These fish regularly visit cleaner wrasses Labroides dimidiatus to have ectoparasites removed. The cleanerfish influences client decisions by physically touching the surgeonfish with its pectoral and pelvic fins, a behaviour known as tactile stimulation. We simulated this behaviour by exposing surgeonfish to mechanically moving cleanerfish models. Surgeonfish had significantly lower levels of cortisol when stimulated by moving models compared with controls with access to stationary models. Our results show that physical contact alone, without a social aspect, is enough to produce fitness-enhancing benefits, a situation so far only demonstrated in humans. PMID:22086335

  7. Optogenetic stimulation of myelination (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yang, In Hong; Lee, Hae Ung; Thakor, Nitish V.

    2016-03-01

    Myelination is governed by axon-glia interaction which is modulated by neural activity. Currently, the effects of subcellular activation of neurons which induce neural activity upon myelination are not well understood. To identify if subcellular neuronal stimulation can enhance myelination, we developed a novel system for focal stimulation of neural activity with optogenetic in a compartmentalized microfluidic platform. In our systems, stimulation for neurons in restricted subcellular parts, such as cell bodies and axons promoted oligodendrocyte differentiation and the myelination of axons the just as much as whole cell activation of neurons did. The number of premature O4 positive oligodendrocytes was reduced and the numbers of mature and myelin basic protein-positive oligodendrocytes was increased both by subcellular optogenetic stimulation.

  8. Electroencephalographic responses to intraoperative subthalamic stimulation.

    PubMed

    Colloca, Luana; Benedetti, Fabrizio; Bergamasco, Bruno; Vighetti, Sergio; Zibetti, Maurizio; Ducati, Alessandro; Lanotte, Michele; Lopiano, Leonardo

    2006-10-01

    This study reports the effects of intraoperative stimulation of the subthalamic nucleus on brain electrical activity in advanced Parkinson's patients. To our knowledge, this is the first study about electroencephalographic responses in the very early phase of deep brain stimulation, during the implantation of the electrodes. We found an increase of gamma band bilaterally over the sensorimotor cortex in the range 45-55 Hz, which was associated with clinical improvement as assessed by means of muscle rigidity decrease. These results indicate that the electroencephalographic gamma responses to deep brain stimulation are present at the very beginning of the treatment process, and may help better understand the short and long-tem effects of deep brain stimulation.

  9. Imbibition well stimulation via neural network design

    DOEpatents

    Weiss, William

    2007-08-14

    A method for stimulation of hydrocarbon production via imbibition by utilization of surfactants. The method includes use of fuzzy logic and neural network architecture constructs to determine surfactant use.

  10. Cardiovascular effects of afferent renal nerve stimulation.

    PubMed

    Stella, A; Weaver, L; Golin, R; Genovesi, S; Zanchetti, A

    1987-01-01

    Electrical stimulation of afferent renal nerves elicits an increase in arterial pressure and heart rate. The hypertensive response is presumably due to the widespread activation of the sympathetic nervous system leading to peripheral vasoconstriction. Interestingly, the kidney does not appear involved in this reflex excitatory response to afferent renal nerve stimulation since changes in vascular conductances and excretory functions are equal in both the innervated and denervated kidney, and secondary to changes in renal perfusion pressure. In addition, no changes in renin release from either kidneys are observed during afferent renal nerve stimulation. It is likely that the electrical stimulation of afferent renal nerves activates other reflexes exerting an inhibitory influence on efferent renal nerve activity. Indeed, neural renorenal reflexes which tonically inhibit renal functions have clearly been demonstrated. Furthermore, preferential inhibition of efferent renal nerve activity by cardiopulmonary and sinoaortic receptors has recently been shown during activation of other visceral afferents.

  11. Optogenetic stimulation of MCH neurons increases sleep.

    PubMed

    Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Zayachkivsky, Andrew; Liu, Meng; Uhde, Thomas; Glen, W Bailey; van den Pol, Anthony N; Mulholland, Patrick J; Shiromani, Priyattam J

    2013-06-19

    Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia.

  12. [Stimulation of spermatogenesis: For whom? Why? How?].

    PubMed

    Bertrand-Delepine, J; Leroy, C; Rigot, J-M; Catteau-Jonard, S; Dewailly, D; Robin, G

    2016-09-01

    The stimulation of spermatogenesis is the best treatment of infertility for male hypogonadotropic-hypogonadism. The results are very pleasing because a real improvement of semen is sometimes obtained with spontaneous pregnants describing in the literature but after a long duration of treatment, often many months. Sometimes, the treatment improves the technical conditions of ICSI for the embryologists. Stimulation of spermatogenesis by gonadotrophins rFSH and/or hCG is the most used but others treatments, like pulsatile GnRH therapy or clomifene citrate can be used. The purpose of this review is to described the different protocols of stimulation of spermatogenesis and explain their results and finally to see if others indications of stimulation of spermatogenesis are existing. PMID:27475410

  13. Calpain 11 Is Unique to Mouse Spermatogenic Cells

    PubMed Central

    Ben-Aharon, Irit; Brown, Paula R.; Shalgi, Ruth; Eddy, Edward M.

    2007-01-01

    The calpains are a family of calcium-dependent thiol proteases involved in intracellular processing of proteins. They occur as heterodimers containing one of various large subunits and a common small subunit. Some of the large subunits are expressed ubiquitously and others are expressed in a restricted set of tissues. We have cloned the cDNA for mouse calpain 11 and demonstrated that it is expressed specifically in the mouse testis. The mRNA begins to accumulate in the testis between days 14 and 16 days after birth, corresponding to the period of pachytene spermatocyte development. The protein is detected by day 18 after birth, during mid to late pachytene spermatocyte development, and is present in the acrosomal region of spermatozoa from the cauda epididymis. The expression of calpain 11 during spermatogenesis and its localization is spermatozoa suggest that it is involved in regulating calcium-dependent signal transduction events during meiosis and sperm functional processes. PMID:16541461

  14. Transcranial magnetic stimulation and the human brain

    NASA Astrophysics Data System (ADS)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  15. Intramolecular motion during stimulated surface processes

    SciTech Connect

    Burns, A.R.; Jennison, D.R.; Stechel, E.B. ); Li, Y.S. )

    1994-06-13

    Ammonia and deuterated ammonia exhibit an anomalously large isotope effect in their relative yields and rotational spinning energy for electron-stimulated desorption from Pt(111). Quantum-resolved desorption measurements and [ital ab] [ital initio], two-dimensional, potential energy calculations suggest that the desorbate undergoes a geometry change (molecular inversion) induced by the excited state. Inverted molecules deexcite to a repulsive hard wall potential and desorb. In general, [ital multidimensional] potential energy surfaces determine the dynamics of stimulated surface processes.

  16. Enhanced Cultivation Of Stimulated Murine B Cells

    NASA Technical Reports Server (NTRS)

    Sammons, David W.

    1994-01-01

    Method of in vitro cultivation of large numbers of stimulated murine B lymphocytes. Cells electrofused with other cells to produce hybridomas and monoclonal antibodies. Offers several advantages: polyclonally stimulated B-cell blasts cultivated for as long as 14 days, hybridomas created throughout culture period, yield of hybridomas increases during cultivation, and possible to expand polyclonally in vitro number of B cells specific for antigenic determinants first recognized in vivo.

  17. Closing the loop of deep brain stimulation

    PubMed Central

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-01-01

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

  18. Closing the loop of deep brain stimulation.

    PubMed

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-01-01

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

  19. Effect of neurovestibular stimulation on autonomic regulation

    NASA Technical Reports Server (NTRS)

    Costa, F.; Lavin, P.; Robertson, D.; Biaggioni, I.

    1995-01-01

    Conditions associated with nausea and vomiting, such as motion sickness or side effects of medications, are commonly associated with a clinical picture consistent with parasympathetic activation and sympathetic withdrawal. It can be postulated, therefore, that vestibular stimulation contributes to sympathetic withdrawal. To test this hypothesis five normal volunteers, 24-33 years old, were studied during caloric vestibular stimulation while monitoring muscle sympathetic nerve activity directly through a needle electrode placed in a peroneal nerve. The ear was irrigated with water at a flow rate of 450 ml/min and 37 degrees C. The water temperature was sequentially lowered by 7 degree C intervals until intolerable side effects developed or a temperature of 16 degrees C was reached. Nystagmus was induced in all subjects, but heart rate, blood pressure, muscle sympathetic nerve activity and plasma norepinephrine levels did not change significantly during or after caloric stimulation, even when the subjects felt dizzy and nauseated. No evidence of sympathetic withdrawal was observed in any subject either by muscle sympathetic nerve activity or plasma norepinephrine measurements. In conclusion, we have found that selective vestibular stimulation is not accompanied by significant changes in the sympathetic nervous system function. In particular, no sympathetic withdrawal was observed. It could be argued that lack of sympathetic stimulation is an inadequate response to the symptoms associated with caloric stimulation.

  20. Chronic network stimulation enhances evoked action potentials

    NASA Astrophysics Data System (ADS)

    Ide, A. N.; Andruska, A.; Boehler, M.; Wheeler, B. C.; Brewer, G. J.

    2010-02-01

    Neurons cultured on multielectrode arrays almost always lack external stimulation except during the acute experimental phase. We have investigated the effects of chronic stimulation during the course of development in cultured hippocampal neural networks by applying paired pulses at half of the electrodes for 0, 1 or 3 r/day for 8 days. Spike latencies increased from 4 to 16 ms as the distance from the stimulus increased from 200 to 1700 µm, suggesting an average of four synapses over this distance. Compared to no chronic stimulation, our results indicate that chronic stimulation increased evoked spike counts per stimulus by 50% at recording sites near the stimulating electrode and increased the instantaneous firing rate. On trials where both pulses elicited responses, spike count was 40-80% higher than when only one of the pulses elicited a response. In attempts to identify spike amplitude plasticity, we found mainly amplitude variation with different latencies suggesting recordings from neurons with different identities. These data suggest plastic network changes induced by chronic stimulation that enhance the reliability of information transmission and the efficiency of multisynaptic network communication.

  1. Considering optogenetic stimulation for cochlear implants.

    PubMed

    Jeschke, Marcus; Moser, Tobias

    2015-04-01

    Electrical cochlear implants are by far the most successful neuroprostheses and have been implanted in over 300,000 people worldwide. Cochlear implants enable open speech comprehension in most patients but are limited in providing music appreciation and speech understanding in noisy environments. This is generally considered to be due to low frequency resolution as a consequence of wide current spread from stimulation contacts. Accordingly, the number of independently usable stimulation channels is limited to less than a dozen. As light can be conveniently focused, optical stimulation might provide an alternative approach to cochlear implants with increased number of independent stimulation channels. Here, we focus on summarizing recent work on optogenetic stimulation as one way to develop optical cochlear implants. We conclude that proof of principle has been presented for optogenetic stimulation of the cochlea and central auditory neurons in rodents as well as for the technical realization of flexible μLED-based multichannel cochlear implants. Still, much remains to be done in order to advance the technique for auditory research and even more for eventual clinical translation. This article is part of a Special Issue entitled . PMID:25601298

  2. A microprocessor-based multichannel subsensory stochastic resonance electrical stimulator.

    PubMed

    Chang, Gwo-Ching

    2013-01-01

    Stochastic resonance electrical stimulation is a novel intervention which provides potential benefits for improving postural control ability in the elderly, those with diabetic neuropathy, and stroke patients. In this paper, a microprocessor-based subsensory white noise electrical stimulator for the applications of stochastic resonance stimulation is developed. The proposed stimulator provides four independent programmable stimulation channels with constant-current output, possesses linear voltage-to-current relationship, and has two types of stimulation modes, pulse amplitude and width modulation.

  3. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life. PMID:20885119

  4. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life.

  5. Parameter exploration of staircase-shape extracellular stimulation for targeted stimulation of myelinated axon.

    PubMed

    Ueno, Ayako; Karashima, Akihiro; Nakao, Mitsuyuki; Katayama, Norihiro

    2011-01-01

    Spatio-temporal dynamics of a mathematical model of myelinated axon in response to staircase-shape extracellular electrical stimulation, which was developed for selective nerve stimulation, is investigated by the computer simulation. It is shown that the response is classified into four types: subthreshold response, cathodic excitation, anodal block and anodal break excitation. Based on the simulation results, simple diagrams representing the response characteristics of the axon are constructed as functions of stimulation parameters and distance between the axon and electrode. The diagram would be useful for determining simulation parameters for dynamic targeted stimulation of myelinated axon. PMID:22254459

  6. Ring-shaped backward stimulated Raman scattering driven by stimulated Brillouin scattering.

    PubMed

    Feng, Chengyong; Diels, Jean-Claude; Xu, Xiaozhen; Arissian, Ladan

    2015-06-29

    Backward stimulated Raman scattering is generated in water, pumped by pre-compressed pulses from a single-cell stimulated Brillouin scattering pulse compressor. The maximum energy efficiency of 9% is achieved by employing a circularly-polarized pump pulse at its energy of 50 mJ, around which point the backward stimulated Raman scattering also exhibits a ring-shaped profile. The correlations between spatial and temporal profiles as well as the intensities of the backward stimulated Raman and the stimulated Brillouin scattering generated from Raman cell indicate that the ring-shaped backward stimulated Raman is driven by intense stimulated Brillouin scattering. We demonstrate the latter process to be much more efficient for the backward Raman generation than the conventional process in which the laser itself pumps a backward stimulated Raman beam. It is shown that a further increase in pump energy leads to a drop in efficiency, combined with a break-up of the ring pattern of backward stimulated Raman. These effects are associated with filament generation above a certain threshold.

  7. Aversive hypothalamic stimulation releases acetylcholine in the nucleus accumbens, and stimulation-escape decreases it.

    PubMed

    Rada, P V; Hoebel, B G

    2001-01-01

    Hypothalamic electrodes can generate positive reinforcement, as shown by self-stimulation, and negative reinforcement shown by stimulation-escape. It was hypothesized that acetylcholine (ACh) is released in the nucleus accumbens during the aversive state that underlies stimulation-escape. If this is correct, escape behavior should lower extracellular ACh. Rats were prepared with microdialysis probes in the accumbens (posterior shell region) and electrodes in the perifornical lateral hypothalamus. Animals learned to press a lever for 0.5 s trains of stimulation (typically 3600 responses/h). Then they were given automatic stimulation to determine which animals would also learn to press a lever to turn stimulation off for 5 s at a time (typically 75 responses/h). Accumbens microdialysis showed that automatic stimulation caused extracellular ACh to double, but only in the rats that were motivated to learn stimulation-escape. When allowed to escape stimulation, these animals lowered extracellular ACh significantly. It is concluded that ACh release in the accumbens is related to the neural state that animals work to escape.

  8. Hydraulic Fracture Stimulation and Acid Treatment of Well Baca 20; Geothermal Reservoir Well Stimulation Program

    SciTech Connect

    1983-07-01

    The U.S. Department of Energy-sponsored Geothermal Reservoir Well Stimulation Program was initiated in February 1979 to pursue industry interest in geothermal well stimulation work and to develop technical expertise in areas directly related to geothermal well stimulation activities. This report provides an overview of the two experiments conducted in the high-temperature reservoir in Baca, New Mexico. The report discusses resource and reservoir properties, and provides a description of the stimulation experiment, a description of the treatment evaluation, and a summary of the experiment costs. (DJE-2005)

  9. Cortical responses to C-fiber stimulation by intra-epidermal electrical stimulation: an MEG study.

    PubMed

    Motogi, Jun; Kodaira, Minori; Muragaki, Yoshihiro; Inui, Koji; Kakigi, Ryusuke

    2014-06-01

    Intra-epidermal electric stimulation (IES) is an alternative to laser stimulation for selective activation of cutaneous Aδ-fibers. IES is based on the fact that nociceptive fiber terminals are located in the epidermis, whereas receptors of other fibers end deep in the dermis. IES can selectively stimulate C-fibers if the electrode structure and stimulation parameters are carefully selected. However, stable selective stimulation of C-fibers using IES has proven difficult and cannot currently be used in clinical settings. The purpose of the present study was to determine if IES performed using a modified electrode reliably stimulates C-fibers. Magnetoencephalographic responses to IES to the foot were measured in seven healthy subjects. IES elicited somatosensory evoked fields in all subjects. The mean peak latency was 1,327 ± 116 ms in the opercular region contralateral to the stimulated side, 1,318 ± 90 ms in the opercular region ipsilateral to the stimulated side, and 1350 ± 139 ms in the primary somatosensory cortex. These results indicate that IES performed using the modified electrode can selectively stimulate C-fibers and may be a useful tool for pain research as well as clinical evaluation of peripheral small fiber function.

  10. Radiant energy required for infrared neural stimulation

    SciTech Connect

    Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; Xia, Nan; Stock, Stuart R.; Xiao, Xianghui; Richter, Claus-Peter

    2015-08-25

    Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography was used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm2, respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.

  11. Radiant energy required for infrared neural stimulation

    DOE PAGES

    Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; Xia, Nan; Stock, Stuart R.; Xiao, Xianghui; Richter, Claus-Peter

    2015-08-25

    Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography wasmore » used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm2, respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.« less

  12. Stimulants for the Control of Hedonic Appetite.

    PubMed

    Poulton, Alison S; Hibbert, Emily J; Champion, Bernard L; Nanan, Ralph K H

    2016-01-01

    The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug.

  13. Impulsivity, Stimulant Abuse, and Dopamine Receptor Signaling.

    PubMed

    London, E D

    2016-01-01

    The nonmedical use of amphetamine-type stimulants is a worldwide problem, with substantial medical and social consequences. Nonetheless, the identification of a pharmacological treatment for amphetamine use disorder remains elusive. Stimulant users exhibit neurochemical evidence of dopamine-system dysfunction as well as impulsive behaviors that may interfere with the success of treatments for their addiction. This review focuses on the potential role of dopaminergic neurotransmission in impulsivity, both in healthy individuals and chronic stimulant users who meet criteria for methamphetamine dependence. Presented are findings related to the potential contributions of signaling through dopamine D1- and D2-type receptors to self-control impulsivity in methamphetamine- dependent users. The information available points to signaling through striatal D2-type dopamine receptors as a potential therapeutic target for stimulant use disorders, but medications that target D2-type dopamine receptors have not been successful in treating stimulant-use disorders, possibly because D2-type receptors are downregulated. Other means to augment D2-type receptor signaling are therefore under consideration, and one promising approach is the addition of exercise training as an adjunct to behavioral treatment for addiction. PMID:27288074

  14. Radiant energy required for infrared neural stimulation

    PubMed Central

    Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; Xia, Nan; Stock, Stuart R.; Xiao, Xianghui; Richter, Claus-Peter

    2015-01-01

    Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography was used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm2, respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS. PMID:26305106

  15. Dynamics of stimulated L → H transitions

    SciTech Connect

    Miki, K.; Diamond, P. H.; Xiao, W. W.; Hahn, S.-H.; Gürcan, Ö. D.; Tynan, G. R.

    2013-08-15

    We report on model studies of stimulated L → H transitions [K. Miki et al., Phys. Rev. Lett. 110, 195002 (2013)]. These studies use a reduced mesoscale model. Model studies reveal that L → H transition can be triggered by particle injection into a subcritical state (i.e., Pstimulated transition. For low ambient heating, strong injection is predicted to trigger a transient turbulence collapse. Repetitive injection at a period less than the lifetime of the collapsed state can thus maintain the turbulence collapse and so sustain a driven H-mode-like state. The total number of particles required to induce a transition by either injection or gas puffing is estimated. Results indicate that the total number of injected particles required is much smaller than that required for a transition by gas puffing. We thus show that internal injection is more efficient than gas puffing of comparable strength. We also observe that zonal flows do not play a critical role in stimulated transitions. For spontaneous transitions, the spike of the Reynolds work of turbulence on the zonal flow precedes the spike in the mean electric field shear. In contrast, we show that the two are coincident for stimulated transitions, suggesting that there is no causal link between zonal and mean flows for stimulated transitions.

  16. Stimulants for the Control of Hedonic Appetite

    PubMed Central

    Poulton, Alison S.; Hibbert, Emily J.; Champion, Bernard L.; Nanan, Ralph K. H.

    2016-01-01

    The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug. PMID:27199749

  17. Radiant energy required for infrared neural stimulation.

    PubMed

    Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; Xia, Nan; Stock, Stuart R; Xiao, Xianghui; Richter, Claus-Peter

    2015-08-25

    Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography was used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm(2), respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS.

  18. Technological Advances in Deep Brain Stimulation.

    PubMed

    Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

    2015-01-01

    Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware. PMID:26406128

  19. Noninvasive brain stimulation improves language learning.

    PubMed

    Flöel, Agnes; Rösser, Nina; Michka, Olesya; Knecht, Stefan; Breitenstein, Caterina

    2008-08-01

    Anodal transcranial direct current stimulation (tDCS) is a reliable technique to improve motor learning. We here wanted to test its potential to enhance associative verbal learning, a skill crucial for both acquiring new languages in healthy individuals and for language reacquisition after stroke-induced aphasia. We applied tDCS (20 min, 1 mA) over the posterior part of the left peri-sylvian area of 19 young right-handed individuals while subjects acquired a miniature lexicon of 30 novel object names. Every subject participated in one session of anodal tDCS, one session of cathodal tDCS, and one sham session in a randomized and double-blinded design with three parallel versions of the miniature lexicon. Outcome measures were learning speed and learning success at the end of each session, and the transfer to the subjects' native language after the respective stimulation. With anodal stimulation, subjects showed faster and better associative learning as compared to sham stimulation. Mood ratings, reaction times, and response styles were comparable between stimulation conditions. Our results demonstrate that anodal tDCS is a promising technique to enhance language learning in healthy adults and may also have the potential to improve language reacquisition after stroke.

  20. An implantable neural stimulator for intraspinal microstimulation.

    PubMed

    Troyk, Philip R; Mushahwar, Vivian K; Stein, Richard B; Suh, Sungjae; Everaert, Dirk; Holinski, Brad; Hu, Zhe; DeMichele, Glenn; Kerns, Douglas; Kayvani, Kevin

    2012-01-01

    This paper reports on a wireless stimulator device for use in animal experiments as part of an ongoing investigation into intraspinal stimulation (ISMS) for restoration of walking in humans with spinal cord injury. The principle behind using ISMS is the activation of residual motor-control neural networks within the spinal cord ventral horn below the level of lesion following a spinal cord injury. The attractiveness to this technique is that a small number of electrodes can be used to induce bilateral walking patterns in the lower limbs. In combination with advanced feedback algorithms, ISMS has the potential to restore walking for distances that exceed that produced by other types of functional electrical stimulation. Recent acute animal experiments have demonstrated the feasibility of using ISMS to produce the coordinated walking patterns. Here we described a wireless implantable stimulation system to be used in chronic animal experiments and for providing the basis for a system suitable for use in humans. Electrical operation of the wireless system is described, including a demonstration of reverse telemetry for monitoring the stimulating electrode voltages. PMID:23366038

  1. Technological Advances in Deep Brain Stimulation.

    PubMed

    Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

    2015-01-01

    Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware.

  2. Stimulation of neutrophils by tumor necrosis factor

    SciTech Connect

    Klebanoff, S.J.; Vadas, M.A.; Harlan, J.M.; Sparks, L.H.; Gamble, J.R.; Agosti, J.M.; Waltersdorph, A.M.

    1986-06-01

    Human recombinant tumor necrosis factor (TNF) was shown to be a weak direct stimulus of the neutrophil respiratory burst and degranulation. The stimulation, as measured by iodination, H/sub 2/O/sub 2/ production, and lysozyme release, was considerably increased by the presence of unopsonized zymosan in the reaction mixture, an effect which was associated with the increased ingestion of the zymosan. TNF does not act as an opsonin but, rather, reacts with the neutrophil to increase its phagocytic activity. TNF-dependent phagocytosis, as measured indirectly by iodination, is inhibited by monoclonal antibodies (Mab) 60.1 and 60.3, which recognize different epitopes on the C3bi receptor/adherence-promoting surface glycoprotein of neutrophils. Other neutrophil stimulants, namely N-formyl-methionyl-leucyl-phenylalanine, the Ca2+ ionophore A23187, and phorbol myristic acetate, also increase iodination in the presence of zymosan; as with TNF, the effect of these stimulants is inhibited by Mab 60.1 and 60.3, whereas, in contrast to that of TNF, their stimulation of iodination is unaffected by an Mab directed against TNF. TNF may be a natural stimulant of neutrophils which promotes adherence to endothelial cells and to particles, leading to increased phagocytosis, respiratory burst activity, and degranulation.

  3. Stimulants for the Control of Hedonic Appetite.

    PubMed

    Poulton, Alison S; Hibbert, Emily J; Champion, Bernard L; Nanan, Ralph K H

    2016-01-01

    The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug. PMID:27199749

  4. Radiant energy required for infrared neural stimulation.

    PubMed

    Tan, Xiaodong; Rajguru, Suhrud; Young, Hunter; Xia, Nan; Stock, Stuart R; Xiao, Xianghui; Richter, Claus-Peter

    2015-01-01

    Infrared neural stimulation (INS) has been proposed as an alternative method to electrical stimulation because of its spatial selective stimulation. Independent of the mechanism for INS, to translate the method into a device it is important to determine the energy for stimulation required at the target structure. Custom-designed, flat and angle polished fibers, were used to deliver the photons. By rotating the angle polished fibers, the orientation of the radiation beam in the cochlea could be changed. INS-evoked compound action potentials and single unit responses in the central nucleus of the inferior colliculus (ICC) were recorded. X-ray computed tomography was used to determine the orientation of the optical fiber. Maximum responses were observed when the radiation beam was directed towards the spiral ganglion neurons (SGNs), whereas little responses were seen when the beam was directed towards the basilar membrane. The radiant exposure required at the SGNs to evoke compound action potentials (CAPs) or ICC responses was on average 18.9 ± 12.2 or 10.3 ± 4.9 mJ/cm(2), respectively. For cochlear INS it has been debated whether the radiation directly stimulates the SGNs or evokes a photoacoustic effect. The results support the view that a direct interaction between neurons and radiation dominates the response to INS. PMID:26305106

  5. Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

    PubMed Central

    2011-01-01

    Background Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold. Methods The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects. Results Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs. Conclusions To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes. PMID:21306616

  6. Infrared neural stimulation: a new stimulation tool for central nervous system applications

    PubMed Central

    Chernov, Mykyta; Roe, Anna Wang

    2014-01-01

    Abstract. The traditional approach to modulating brain function (in both clinical and basic science applications) is to tap into the neural circuitry using electrical currents applied via implanted electrodes. However, it suffers from a number of problems, including the risk of tissue trauma, poor spatial specificity, and the inability to selectively stimulate neuronal subtypes. About a decade ago, optical alternatives to electrical stimulation started to emerge in order to address the shortcomings of electrical stimulation. We describe the use of one optical stimulation technique, infrared neural stimulation (INS), during which short (of the order of a millisecond) pulses of infrared light are delivered to the neural tissue. Very focal stimulation is achieved via a thermal mechanism and stimulation location can be quickly adjusted by redirecting the light. After describing some of the work done in the peripheral nervous system, we focus on the use of INS in the central nervous system to investigate functional connectivity in the visual and somatosensory areas, target specific functional domains, and influence behavior of an awake nonhuman primate. We conclude with a positive outlook for INS as a tool for safe and precise targeted brain stimulation. PMID:26157967

  7. The Effect of Early Stimulation: The Problem of Focus in Developmental Stimulation.

    ERIC Educational Resources Information Center

    Fowler, William

    Studies of the effect of environmental stimulation on an individual's development in either general or specific ability conclude that some specific stimulation should be introduced at an early age while a child is still malleable. An intense, persistent, and regular tutorial approach within the family encourages the development of a special talent…

  8. Magnetic fields in noninvasive brain stimulation.

    PubMed

    Vidal-Dourado, Marcos; Conforto, Adriana Bastos; Caboclo, Luis Otávio Sales Ferreira; Scaff, Milberto; Guilhoto, Laura Maria de Figueiredo Ferreira; Yacubian, Elza Márcia Targas

    2014-04-01

    The idea that magnetic fields could be used therapeutically arose 2000 years ago. These therapeutic possibilities were expanded after the discovery of electromagnetic induction by the Englishman Michael Faraday and the American Joseph Henry. In 1896, Arsène d'Arsonval reported his experience with noninvasive brain magnetic stimulation to the scientific French community. In the second half of the 20th century, changing magnetic fields emerged as a noninvasive tool to study the nervous system and to modulate neural function. In 1985, Barker, Jalinous, and Freeston presented transcranial magnetic stimulation, a relatively focal and painless technique. Transcranial magnetic stimulation has been proposed as a clinical neurophysiology tool and as a potential adjuvant treatment for psychiatric and neurologic conditions. This article aims to contextualize the progress of use of magnetic fields in the history of neuroscience and medical sciences, until 1985. PMID:23787954

  9. Metabolism of the stimulated rat spleen

    PubMed Central

    Mazur, Abraham

    1968-01-01

    Assay of the enzyme ferrochelatase in marrow, liver, spleen, and red cells has been employed to assess the extent of erythropoietic stimulation in animals bearing the Walker 256 carcinosarcoma and in rats treated by administration of phenylhydrazine, cobalt chloride, human urinary erythropoietin, or chronic blood loss. In all instances, the spleen sustains the most marked increase of ferrochelatase activity, per gram of tissue. Spleen erythropoietic activity stimulation was confirmed by quantitative measurements in respiring slices of 59Fe and 14C incorporation into hemoglobin and ferritin. Increased spleen ferrochelatase activity in cobalt chloride-treated rats is prevented by actinomycin D, indicating that stimulated synthesis of the enzyme is associated with the metabolism of RNA. PMID:5676519

  10. Magnetic fields in noninvasive brain stimulation.

    PubMed

    Vidal-Dourado, Marcos; Conforto, Adriana Bastos; Caboclo, Luis Otávio Sales Ferreira; Scaff, Milberto; Guilhoto, Laura Maria de Figueiredo Ferreira; Yacubian, Elza Márcia Targas

    2014-04-01

    The idea that magnetic fields could be used therapeutically arose 2000 years ago. These therapeutic possibilities were expanded after the discovery of electromagnetic induction by the Englishman Michael Faraday and the American Joseph Henry. In 1896, Arsène d'Arsonval reported his experience with noninvasive brain magnetic stimulation to the scientific French community. In the second half of the 20th century, changing magnetic fields emerged as a noninvasive tool to study the nervous system and to modulate neural function. In 1985, Barker, Jalinous, and Freeston presented transcranial magnetic stimulation, a relatively focal and painless technique. Transcranial magnetic stimulation has been proposed as a clinical neurophysiology tool and as a potential adjuvant treatment for psychiatric and neurologic conditions. This article aims to contextualize the progress of use of magnetic fields in the history of neuroscience and medical sciences, until 1985.

  11. Motilin stimulates pepsinogen secretion in Suncus murinus.

    PubMed

    Goswami, Chayon; Tanaka, Toru; Jogahara, Takamichi; Sakai, Takafumi; Sakata, Ichiro

    2015-07-01

    Motilin and ghrelin are gastrointestinal hormones that stimulate the migrating motor complex (MMC) of gastrointestinal motility during the fasting state. In this study, we examined the effect of motilin and ghrelin on pepsinogen secretion in anesthetized suncus (house musk shrew, Suncus murinus), a ghrelin- and motilin-producing mammal. By using a gastric lumen-perfusion system, we found that the intravenous administration of carbachol and motilin stimulated pepsinogen secretion, the latter in a dose-dependent manner, whereas ghrelin had no effect. We then investigated the pathways of motilin-induced pepsinogen secretion using acetylcholine receptor antagonists. Treatment with atropine, a muscarinic acetylcholine receptor antagonist, completely inhibited both carbachol and motilin-induced pepsinogen secretion. Motilin-induced pepsinogen secretion was observed in the vagotomized suncus. This is the first report demonstrating that motilin stimulates pepsinogen secretion, and suggest that this effect occurs through a cholinergic pathway in suncus. PMID:25957475

  12. High frequency stimulation can block axonal conduction.

    PubMed

    Jensen, Alicia L; Durand, Dominique M

    2009-11-01

    High frequency stimulation (HFS) is used to control abnormal neuronal activity associated with movement, seizure, and psychiatric disorders. Yet, the mechanisms of its therapeutic action are not known. Although experimental results have shown that HFS suppresses somatic activity, other data has suggested that HFS could generate excitation of axons. Moreover it is unclear what effect the stimulation has on tissue surrounding the stimulation electrode. Electrophysiological and computational modeling literature suggests that HFS can drive axons at the stimulus frequency. Therefore, we tested the hypothesis that unlike cell bodies, axons are driven by pulse train HFS. This hypothesis was tested in fibers of the hippocampus both in-vivo and in-vitro. Our results indicate that although electrical stimulation could activate and drive axons at low frequencies (0.5-25 Hz), as the stimulus frequency increased, electrical stimulation failed to continuously excite axonal activity. Fiber tracts were unable to follow extracellular pulse trains above 50 Hz in-vitro and above 125 Hz in-vivo. The number of cycles required for failure was frequency dependent but independent of stimulus amplitude. A novel in-vitro preparation was developed, in which, the alveus was isolated from the remainder of the hippocampus slice. The isolated fiber tract was unable to follow pulse trains above 75 Hz. Reversible conduction block occurred at much higher stimulus amplitudes, with pulse train HFS (>150 Hz) preventing propagation through the site of stimulation. This study shows that pulse train HFS affects axonal activity by: (1) disrupting HFS evoked excitation leading to partial conduction block of activity through the site of HFS; and (2) generating complete conduction block of secondary evoked activity, as HFS amplitude is increased. These results are relevant for the interpretation of the effects of HFS for the control of abnormal neural activity such as epilepsy and Parkinson's disease. PMID

  13. Oxidants as stimulators of signal transduction.

    PubMed

    Suzuki, Y J; Forman, H J; Sevanian, A

    1997-01-01

    Redox (oxidation-reduction) reactions regulate signal transduction. Oxidants such as superoxide, hydrogen peroxide, hydroxyl radicals, and lipid hydroperoxides (i.e., reactive oxygen species) are now realized as signaling molecules under subtoxic conditions. Nitric oxide is also an example of a redox mediator. Reactive oxygen species induce various biological processes such as gene expression by stimulating signal transduction components such as Ca(2+)-signaling and protein phosphorylation. Various oxidants increase cytosolic Ca2+; however, the exact origin of Ca2+ is controversial. Ca2+ may be released from the endoplasmic reticulum, extracellular space, or mitochondria in response to oxidant-influence on Ca2+ pumps, channels, and transporters. Alternatively, oxidants may release Ca2+ from Ca2+ binding proteins. Various oxidants stimulate tyrosine as well as serine/threonine phosphorylation, and direct stimulation of protein kinases and inhibition of protein phosphatases by oxidants have been proposed as mechanisms. The oxidant-stimulation of the effector molecules such as phospholipase A2 as well as the activation of oxidative stress-responsive transcription factors may also depend on the oxidant-mediated activation of Ca(2+)-signaling and/or protein phosphorylation. In addition to the stimulation of signal transduction by oxidants, the observations that ligand-receptor interactions produce reactive oxygen species and that antioxidants block receptor-mediated signal transduction led to a proposal that reactive oxygen species may be second messengers for transcription factor activation, apoptosis, bone resorption, cell growth, and chemotaxis. Physiological significance of the role of biological oxidants in the regulation of signal transduction as well as the mechanisms of the oxidant-stimulation of signal transduction are discussed.

  14. 21 CFR 890.5860 - Ultrasound and muscle stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use...

  15. 21 CFR 890.5860 - Ultrasound and muscle stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use...

  16. 21 CFR 890.5860 - Ultrasound and muscle stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use...

  17. 21 CFR 890.5860 - Ultrasound and muscle stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use...

  18. 21 CFR 890.5860 - Ultrasound and muscle stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use...

  19. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  20. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  1. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  2. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  3. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  4. Pudendal Nerve Stimulation and Block by a Wireless Controlled Implantable Stimulator in Cats

    PubMed Central

    Yang, Guangning; Wang, Jicheng; Shen, Bing; Roppolo, James R.; de Groat, William C.; Tai, Changfeng

    2014-01-01

    Objective To determine the functionality of a wireless controlled implantable stimulator designed for stimulation and block of the pudendal nerve. Materials and Methods In 5 cats under α-chloralose anesthesia, the stimulator was implanted underneath the skin on the left side in the lower back along the sacral spine. Two tripolar cuff electrodes were implanted bilaterally on the pudendal nerves in addition to one bipolar cuff electrode that was implanted on the left side central to the tripolar cuff electrode. The stimulator provided high frequency (5-20 kHz) biphasic stimulation waveforms to the two tripolar electrodes and low frequency (1-100 Hz) rectangular pulses to the bipolar electrode. Bladder and urethral pressures were measured to determine the effects of pudendal nerve stimulation (PNS) or block. Results The maximal (70-100 cmH2O) urethral pressure generated by 20 Hz PNS applied via the bipolar electrode was completely eliminated by the pudendal nerve block induced by the high frequency stimulation (6-15 kHz, 6-10 V) applied via the two tripolar electrodes. In a partially filled bladder 20-30 Hz PNS (2-8 V, 0.2 ms) but not 5 Hz stimulation applied via the bipolar electrode elicited a large sustained bladder contraction (45.9±13.4 to 52.0±22 cmH2O). During cystometry, the 5 Hz PNS significantly (P<0.05) increased bladder capacity to 176.5±27.1% of control capacity. Conclusions The wireless controlled implantable stimulator successfully generated the required waveforms for stimulation and block of pudendal nerve, which will be useful for restoring bladder functions after spinal cord injury (SCI). PMID:24320615

  5. Lymphocyte stimulation by soluble subcellular fractions.

    PubMed

    Pegrum, G D; Thompson, E A; Lewis, C M; Grant, V A

    1976-04-01

    Nuclear material can produce inhibition or stimulation of healty leucocytes under different experimental conditions, Reactivity could not be produced in cultures using intact nuclei and allogeneic lymphocytes. The effect of nuclear and cytoplasm fractions was compared with that of whole cells on intact healthy lymphocytes. The HLA activity in the individual fractions was assessed. Stimulation was produced by certain nuclear and cytoplasmic fractions and these were closely related to the peaks of HLA activity. The response to these fractions showed less activity than that achieved in conventional one way MLC tests.

  6. Transcranial laser stimulation improves human cerebral oxygenation

    PubMed Central

    Tian, Fenghua; Hase, Snehal N.

    2016-01-01

    Background and Objective Transcranial laser stimulation of the brain with near‐infrared light is a novel form of non‐invasive photobiomodulation or low‐level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near‐infrared spectroscopy (fNIRS). Materials and Methods Two separate experiments were conducted in which 1,064‐nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2, corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18–40 years old were included in each experiment. Results In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Δ[HbO2]) and a decrease of deoxygenated hemoglobin concentration (Δ[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Δ[HbD] = Δ[HbO2] − Δ[Hb]). These effects increased in a dose‐dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Δ[HbT] = Δ[HbO2] + Δ[Hb]) remained nearly unchanged in most cases. Conclusion Near‐infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans. Lasers Surg. Med. 48:343–349, 2016. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc. PMID:26817446

  7. Deep brain stimulation for movement disorders.

    PubMed

    Thevathasan, Wesley; Gregory, Ralph

    2010-02-01

    Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.

  8. Neural dynamics during repetitive visual stimulation

    NASA Astrophysics Data System (ADS)

    Tsoneva, Tsvetomira; Garcia-Molina, Gary; Desain, Peter

    2015-12-01

    Objective. Steady-state visual evoked potentials (SSVEPs), the brain responses to repetitive visual stimulation (RVS), are widely utilized in neuroscience. Their high signal-to-noise ratio and ability to entrain oscillatory brain activity are beneficial for their applications in brain-computer interfaces, investigation of neural processes underlying brain rhythmic activity (steady-state topography) and probing the causal role of brain rhythms in cognition and emotion. This paper aims at analyzing the space and time EEG dynamics in response to RVS at the frequency of stimulation and ongoing rhythms in the delta, theta, alpha, beta, and gamma bands. Approach.We used electroencephalography (EEG) to study the oscillatory brain dynamics during RVS at 10 frequencies in the gamma band (40-60 Hz). We collected an extensive EEG data set from 32 participants and analyzed the RVS evoked and induced responses in the time-frequency domain. Main results. Stable SSVEP over parieto-occipital sites was observed at each of the fundamental frequencies and their harmonics and sub-harmonics. Both the strength and the spatial propagation of the SSVEP response seem sensitive to stimulus frequency. The SSVEP was more localized around the parieto-occipital sites for higher frequencies (>54 Hz) and spread to fronto-central locations for lower frequencies. We observed a strong negative correlation between stimulation frequency and relative power change at that frequency, the first harmonic and the sub-harmonic components over occipital sites. Interestingly, over parietal sites for sub-harmonics a positive correlation of relative power change and stimulation frequency was found. A number of distinct patterns in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz) and beta (15-30 Hz) bands were also observed. The transient response, from 0 to about 300 ms after stimulation onset, was accompanied by increase in delta and theta power over fronto-central and occipital sites, which returned to baseline

  9. Nucleus accumbens stimulation in pathological obesity.

    PubMed

    Harat, Marek; Rudaś, Marcin; Zieliński, Piotr; Birska, Julita; Sokal, Paweł

    2016-01-01

    One of the potential treatment methods of obesity is deep brain stimulation (DBS) of nucleus accumbens. We describe the case of 19 years old woman with hypothalamic obesity. She weighted 151.4 kg before DBS and the non-surgical methods proved to be inefficient. She was treated with implantation of DBS electrode to nucleus accumbens bilaterally. Results were measured with body mass index and neuropsychological tests. Follow-up was 14 months. Fourteen months after surgery weight was 138 kg, BMI was 48.3. Neuropsychological test results were intact. The presented case supports the thesis of treatment of obesity with nucleus accumbens stimulation. PMID:27154450

  10. Stimulating Cognitive Processes in Beginning Readers.

    ERIC Educational Resources Information Center

    Morgan, Mary Ann; Wallace, Nancy

    Drawing from research on reading, this paper suggests various methods of stimulating cognition in beginning readers. Defining cognition as the process by which a person gains knowledge, or understands or comprehends, discussion in the paper centers on the following topics: (1) perceptive and cognitive skills; (2) prior experience; (3) knowledge of…

  11. Stimulate Students' Interest by Genetics Exordium Teaching

    ERIC Educational Resources Information Center

    Li, Yan

    2009-01-01

    Genetics is the important specialized course of bioscience and whether exordium is taught wonderfully or not plays the important and pivotal role. Well teaching exordium class may stimulate students, deep interest and intense desire for knowledge in this class. This text, according to teaching experience and taste, puts forward several teaching…

  12. Peripheral neural activity recording and stimulation system.

    PubMed

    Loi, D; Carboni, C; Angius, G; Angotzi, G N; Barbaro, M; Raffo, L; Raspopovic, S; Navarro, X

    2011-08-01

    This paper presents a portable, embedded, microcontroller-based system for bidirectional communication (recording and stimulation) between an electrode, implanted in the peripheral nervous system, and a host computer. The device is able to record and digitize spontaneous and/or evoked neural activities and store them in data files on a PC. In addition, the system has the capability of providing electrical stimulation of peripheral nerves, injecting biphasic current pulses with programmable duration, intensity, and frequency. The recording system provides a highly selective band-pass filter from 800 Hz to 3 kHz, with a gain of 56 dB. The amplification range can be further extended to 96 dB with a variable gain amplifier. The proposed acquisition/stimulation circuitry has been successfully tested through in vivo measurements, implanting a tf-LIFE electrode in the sciatic nerve of a rat. Once implanted, the device showed an input referred noise of 0.83 μVrms, was capable of recording signals below 10 μ V, and generated muscle responses to injected stimuli. The results demonstrate the capability of processing and transmitting neural signals with very low distortion and with a power consumption lower than 1 W. A graphic, user-friendly interface has been developed to facilitate the configuration of the entire system, providing the possibility to activate stimulation and monitor recordings in real time.

  13. Quantum theory of laser-stimulated desorption

    NASA Technical Reports Server (NTRS)

    Slutsky, M. S.; George, T. F.

    1978-01-01

    A quantum theory of laser-stimulated desorption (LSDE) is presented and critically analyzed. It is shown how LSDE depends on laser-pulse characteristics and surface-lattice dynamics. Predictions of the theory for a Debye model of the lattice dynamics are compared to recent experimental results.

  14. Stimulating Cultural Appetites: An Experiential Gourmet Approach

    ERIC Educational Resources Information Center

    Chavez, Carolyn I.; Hu Poirier, Vickie

    2007-01-01

    This article is an extension of a presentation that won "Best Exercise" at the Eastern Academy of Management, 1998. The authors introduce an experiential gourmet approach using "food stories" to stimulate an aura of acceptance and appreciation for human commonalities before delving into human differences. The authors use a semester long…

  15. Computer Games Functioning as Motivation Stimulants

    ERIC Educational Resources Information Center

    Lin, Grace Hui Chin; Tsai, Tony Kung Wan; Chien, Paul Shih Chieh

    2011-01-01

    Numerous scholars have recommended computer games can function as influential motivation stimulants of English learning, showing benefits as learning tools (Clarke and Dede, 2007; Dede, 2009; Klopfer and Squire, 2009; Liu and Chu, 2010; Mitchell, Dede & Dunleavy, 2009). This study aimed to further test and verify the above suggestion,…

  16. Magnetic Stimulation Studies of Foveal Representation

    ERIC Educational Resources Information Center

    Lavidor, Michal; Walsh, Vincent

    2004-01-01

    The right and left visual fields each project to the contralateral cerebral hemispheres, but the extent of the functional overlap of the two hemifields along the vertical meridian is still under debate. After presenting the spatial, temporal, and functional specifications of Transcranial Magnetic Stimulation (TMS), we show that TMS is particularly…

  17. Novel transcranial magnetic stimulation coil for mice

    NASA Astrophysics Data System (ADS)

    March, Stephen; Stark, Spencer; Crowther, Lawrence; Hadimani, Ravi; Jiles, David

    2014-03-01

    Transcranial magnetic stimulation (TMS) shows potential for non-invasive treatment of various neurological disorders. Significant work has been performed on the design of coils used for TMS on human subjects but few reports have been made on the design of coils for use on the brains of animals such as mice. This work is needed as TMS studies utilizing mice can allow rapid preclinical development of TMS for human disorders but the coil designs developed for use on humans are inadequate for optimal stimulation of the much smaller mouse brain. A novel TMS coil has been developed with the goal of inducing strong and focused electric fields for the stimulation of small animals such as mice. Calculations of induced electric fields were performed utilizing an MRI derived inhomogeneous model of an adult male mouse. Mechanical and thermal analysis of this new TMS helmet-coil design have also been performed at anticipated TMS operating conditions to ensure mechanical stability of the new coil and establish expected linear attraction and rotational force values. Calculated temperature increases for typical stimulation periods indicate the helmet-coil system is capable of operating within established medical standards. A prototype of the coil has been fabricated and characterization results are presented.

  18. Motor-Cognitive Stimulation of the Elderly

    ERIC Educational Resources Information Center

    Cao, Ana Rey; Lacruz, Inmaculada Canales; Pais, Maria Ines Taboas

    2011-01-01

    This article shows the cognitive and motor-perceptive effects of the application of a cognitive stimulating program through motor function on 234 elderly people. The assessment was carried out prior to and after the program. Significant improvements in the experimental group were observed (p [less than or equal to] 0.05) in six of the eight…

  19. Transcutaneous Electrical Nerve Stimulation: Research Update.

    ERIC Educational Resources Information Center

    Johns, Florene Carnicelli

    Currently, research is being performed in the area of nonsurgical and nonchemical means for influencing the body's threshold for pain. Today, transcutaneous electrical nerve stimulation (TENS) is being widely used for this purpose. Application of this treatment can be confusing, however, because determining such things as selection of the proper…

  20. Causal Measurement Models: Can Criticism Stimulate Clarification?

    ERIC Educational Resources Information Center

    Markus, Keith A.

    2016-01-01

    In their 2016 work, Aguirre-Urreta et al. provided a contribution to the literature on causal measurement models that enhances clarity and stimulates further thinking. Aguirre-Urreta et al. presented a form of statistical identity involving mapping onto the portion of the parameter space involving the nomological net, relationships between the…