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Nathan Goodyear

Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells - 0 views

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    environmental toxin, bisphenol A, shown to increase estrogen receptor and androgen receptor expression in the prostate.  Also, a shift from ER beta to ER alpha occurs, increase the inflammatory and proliferative signal.
Nathan Goodyear

Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells - 0 views

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    Great read on the effects of bisphenol A as an xenoestrogen.  Bisphenol A is a weak estrogen, but it does increase androgen receptor and estrogen receptor alpha transcription.  This is from fetal exposure.
Nathan Goodyear

Fall prevention using olfactory stimulation... [J Am Geriatr Soc. 2012] - PubMed - NCBI - 0 views

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    Lavender essential oil for elderly shown to reduce falls.
Nathan Goodyear

Extranuclear Actions of the Androgen Receptor Enhance Glucose-Stimulated Insulin Secretion in the Male: Cell Metabolism - 0 views

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    only abstract available here. Mouse model finds possible explanation for low Testosterone and diabetes link.  Actually, the link is between the metabolite DHT and the AR. The activity of AR from DHT binding induces beta cell insulin secretion in the presence of glucose.  This is dependent on glucagon-like peptide 1 receptor activation also, which AR activation by DHT does in fact do.
Nathan Goodyear

Telomerase at the intersection of cancer and aging - 0 views

  • The anti-aging role of telomerase has been demonstrated to be largely mediated by its canonical role in elongating telomeres, which prevents the accumulation of critically short telomeres and loss of tissue homeostasis
  • Short telomeres, and subsequent DDR activation, could occur both in cancer and aging
  • increased abundance of short telomeres correlates with higher genomic instability and decreased longevity in various organisms, including mice, zebrafish, and yeast
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  • mice deficient for telomerase or for telomere binding proteins are characterized by accelerated age-related defects
  • In humans, short telomeres are considered good indicators of an individual’s health status and correlate with both genetic and environmental factors
  • Although recent findings strongly support the idea that short telomeres drive several age-related diseases 38 we cannot exclude the possibility that in some situations short telomeres may be a consequence of the disease itself.
  • the current view is that telomerase deficiency may contribute to the early steps of cancer development by fueling chromosomal instability, while subsequent activation of telomerase may be necessary to allow tumor growth and tumor progression towards more malignant states
  • telomerase activation can be an early event in cancer, it is not necessary for cancer initiation
  • telomerase can stimulate tumor progression by ensuring maintenance of telomeres above a critically short length, thus preventing induction of cellular senescence or apoptosis
  • Almost all human cancers present activation of telomerase as a hallmark, most likely as a mechanism to allow unlimited cell proliferation of tumor cells
  • recent evidence demonstrated that short telomeres alone could lead to genomic instability and cancer
  • Getting rid of telomerase can also be problematic; the lack of telomerase could lead to increased chromosomal instability, which in turn could be at the basis for cancer initiation when tumor suppressor barriers are bypassed
  • telomerase activation is a potential therapeutic strategy for the treatment of age-related diseases
  • telomerase activation in adult or old mice by means of a gene therapy strategy was shown to be sufficient to improve metabolic fitness, neuromuscular capacity, and prevent bone loss, as well as significantly increase both median and maximum longevity, without increased cancer incidence
  • These studies suggest that telomerase expression could be considered a feasible approach to reverse tissue dysfunction and extend healthy lifespan without increasing cancer incidence
  • humans almost completely lose telomerase activity from somatic tissues in the adulthood
  • a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging
  • Telomerase expression in a background of high levels of tumor suppressors or in aged organisms seems to prevent its expected pro-cancer activity and yet it still functions as an anti-aging factor
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    Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging.  In contrast, telomerase activity is found to be involved in carcinogenesis.  Increased carcinogenic potential of telomerase activity has not borne out in studies.  In addition, increased CD8 cell activity as a result of telomerase activation will actually decrease carcinogenic potential via NK activation.
Nathan Goodyear

Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects - 0 views

  • At the age of 60, testosterone levels are typically only 40-50% of youthful levels and may be lower
  • Eurycoma contains a group of small peptides referred to as “eurypeptides” that are known to have effects in improving energy status and sex drive in studies of rodents
  • The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG)
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  • The current study found that daily supplementation with tongkat ali root extract (200 mg/day) improves stress hormone profile (lower cortisol; higher testosterone) and certain mood state parameters (lower tension, anger, and confusion)
  • tongkat ali supplementation (100 mg/day) improved lean body mass, 1-RM strength, and arm circumference to a significantly greater degree compared to a placebo group.
  • In a recent 12-week trial [46] of Eurycoma longifolia supplementation (300 mg/day), men (30–55 years of age) showed significant improved compared to placebo in the Physical Functioning domain of the SF-36 quality of life survey
  • sexual libido was increased by 11%
  • In men with low testosterone levels (average age 51 years), one month of daily supplementation with tongkat ali extract (200 mg/day) resulted in a significant improvement in serum testosterone levels and quality-of-life parameters
  • rise in cortisol and drop in testosterone is an early signal of “overtraining”
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    Tongkat Ali, commonly known as long jack, is found to reduce stress and increase Testosterone.  Stress is one of the common causes of low T in men.  It appears that long Jack functions as an adaptogen.
Nathan Goodyear

Bisphenol A Promotes Human Prostate Stem-Progenitor Cell Self-Renewal and Increases In Vivo Carcinogenesis in Human Prostate Epithelium - 0 views

  • these findings show that estrogen stimulates human prostate epithelial stem cell self-renewal and progenitor cell amplification (prostasphere size), with the greatest effects observed at lower E2 doses.
  • Similar to E2, BPA increased prostasphere number and size with significant and maximal effects observed at 10 nM BPA
  • Taken together, these results provide strong evidence that, similar to E2, BPA increases stem cell self-renewal and progenitor amplification in normal human prostate epithelial cells
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  • these findings provide further support that E2 and BPA maintain the stem-like state within the normal prostate epithelial cell population
  • Our previous findings demonstrated that normal prostate stem-progenitor cells within the prostaspheres expressed ERα and ERβ, implicating them as direct targets for E2 and BPA action
  • p-Akt and p-Erk, well established downstream targets of membrane-associated ERs
  • BPA and E2 had equimolar capacity for activation of these rapid signaling pathways in human prostaspheres, thus identifying a dynamic and robust signaling pathway initiated by low-dose BPA exposure in prostate stem-progenitor cells.
  • these findings indicate that both rapid membrane-initiated estrogen action and genomic ER signaling pathways are operative in human prostate progenitor cells.
  • these results document the fact that levels of bioactive BPA in the present study are similar to levels found in human umbilical cord blood and newborns in the general population
  • the present findings identify for the first time that in vivo exposure of the human prostate epithelium to low doses of BPA significantly increases the susceptibility of the human prostate epithelium to hormonal carcinogenesis.
  • The current study provides clear evidence that, similar to E2, normal human prostate stem and progenitor cells are direct targets for BPA action
  • Both hormones increased stem-like cell numbers in primary prostate epithelial cultures in a dose-dependent manner and augmented the number and size of 3-D cultured prostaspheres, markers of stem cell self-renewal and progenitor cell proliferation, respectively
  • signaling pathways engaged by estrogens through these separate receptors are multiple and complex, including both membrane-initiated signaling and genomic activation via ER transcriptional activity
  • Estrogen action is mediated by ERα and ERβ
  • the current results indicate that developmental exposure to BPA, at doses routinely found in humans, significantly increases the cancer risk in human prostate epithelium in response to elevated estrogen levels in an androgen-supported milieu. Because relative estrogen levels rise in aging men, we suggest that humans may be susceptible to BPA-driven prostate disease in a manner similar to that in the rodent models.
  • We propose that early-life perturbations in estrogen signaling including inappropriate exposure to BPA have the potential to amplify and modify the stem-progenitor cell populations within the human prostate gland and, in so doing, alter the normal homeostatic mechanisms that maintain a growth neutral state throughout life
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    Bisphenol A exposure in utero found to increase prostate cancer risk later in life.  This exposure occurred at typical life exposure levels as found in umbilical cord blood sampling,  This occurred through stem cell self-renewal and progenitor amplification
Nathan Goodyear

Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men - 0 views

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    whey protein (20 gm) shown to promote superior muscle growth in older men versus casein and casein hydrolysate.  Whey protein, in this study, was provided at meals, not as a post exercise support.
Nathan Goodyear

Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives - 0 views

  • NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
  • parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
  • estrogen
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  • progesterone
  • prolactin
  • In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
  • At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
  • The exact role of prolactin in NK cell regulation is unknown.
  • The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
  • It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
  • Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
  • Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
  • A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
  • NK cell function is mainly regulated by IL-2 and IFN-γ
  • IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
  • The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
  • there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
  • Second, uNK cell phenotype changes during the normal menstrual cycle and early pregnancy (68)
  • general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
  • The mechanism of such a progesterone-induced local immunosuppression is unclear.
  • progesterone plays an important role in proliferation and differentiation of uNK cells (32).
  • Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
  • The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
  • prolactin system plays an important role in implantation and the maintenance of pregnancy
  • the exact pathways of hormonal regulation of NK cells remain to be delineated.
  • The exact function of uNK cells has not yet been unequivocally determined
  • uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
  • Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
  • role of uNK cell-derived cytokines on trophoblast growth and differentiation (114, 115, 116, 117).
  • Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
  • RPL is associated with Th1 immunity, for which NK cells are partly responsible.
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    dysregulated immune system plays role in recurrent miscarriage.  Specifically, this article discusses natural killer cells (NK).
Nathan Goodyear

Differential Regulation of Gonadotropin Secretion by Testosterone in the Human Male: Absence of a Negative Feedback Effect of Testosterone on Follicle-Stimulating Hormone Secretion - 0 views

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    In men, Testosterone is shown to provide negative feedback on LH; but FSH is primarily regulated by estradiol.
Nathan Goodyear

Stimulation of aromatase activity in bre... [Mol Cell Endocrinol. 1994] - PubMed - NCBI - 0 views

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    inflammatory cytokine, TNF-alpha, increases aromatase activity.  This article discusses the increased production of estrone from androstenedione from aromatase activity in fat tissue in the breast.
Nathan Goodyear

S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders - 0 views

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    SAMe shown to be beneficial as an early response treatment in Hepatitis C. Maybe as a treatment for flu?
Nathan Goodyear

Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels - 1 views

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    increased leptin production results in reduced testosterone production.  Link between leptin associated obesity and resultant low testosterone.
Nathan Goodyear

Salivary cortisol as an alternative for serum cortisol in the low-dose adrenocorticotropic hormone stimulation test? - 0 views

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    salivary cortisol superior to serum cortisol in women on estrogen therapy.
Nathan Goodyear

Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists - 0 views

  • The activated microglia mount a complex local proinflammatory response
  • PPARγ plays a critical role in regulating the inflammatory responses of microglia and monocytes to β-amyloid
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    microglial and inflammatory response in Alzheimer's disease.  Agonists of PPAR-gamma inhibit this action.  This has important implications in reducing the local inflammatory response found in the brains of those with Alzheimers and other neuordegenerative disease.
Nathan Goodyear

Obesity - Inducible Toll-like Receptor and NF-[kappa]B Regulatory Pathway Expression in Human Adipose Tissue - 0 views

  • TLRs are functionally inducible and associated with downstream NF-B activation and proinflammatory cytokine production.
  • TLRs represent a family of receptors that are critical to the innate immune response against foreign pathogens and microorganisms
  • LPS has been shown to induce proinflammatory chemokine gene expression in differentiated human adipocytes through TLR and NF-B action
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  • Stimulation of TLRs initiates intracellular signaling cascades resulting in downstream NF-B and mitogen-activated protein kinase activation and production of proinflammatory chemokines associated with mechanisms of metabolic dysfunction and cardiovascular disease progression.
  • Elevated fatty acids levels associated with obesity activate TLR4 signaling in fat cells and macrophages, and induce insulin resistance in murine models
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    TLR, especially TLR-4, is directly involved in NF-KappaB activation and release of inflammatory cytokines
Nathan Goodyear

Decreased Basal and Stimulated Thyrotropin Secretion in Healthy Elderly Men - 0 views

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    This study shows that older men are associated with low TSH, reduced response to TRH, lowered T3, and normal T4 levels.  The main find in this study was the decrease in pituitary responsiveness to TRH and the reduced TSH as we age.  TSH is unreliable as a test.
Nathan Goodyear

Low Cortisol, High DHEA, and High Levels of Stimulated TNFα, and IL-6 in Women with PTSD - 0 views

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    low cortisol pattern with elevated DHEA found in women with PTSD.  Additionally, elevated levels of TNF-alpha and IL-6 were found. Hormone evaluation was tested through saliva.
Nathan Goodyear

Insulin-stimulated release of D-chiro-inositol-co... [Metabolism. 2008] - PubMed - NCBI - 0 views

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    D-chiro-inositol release correlated with improved insulin sensitivity.
Nathan Goodyear

Cytokine profiles in localized scleroderma and relationship to clinical features - 0 views

  • Evaluation of the literature reveals a Th2 predominant cytokine profile in the biological specimens (sera, PBMCs, and tissue) of those with SSc
  • the literature available from studies in LS show that Th1, Th2, and Th17 cytokines may contribute equally to the pathogenesis of the disease
  • Classically, Th1 cells have been known to secrete IL-2, IFN-γ, and TNF-α, and are stimulated by IL-2 and IL-12
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  • Th2 cells have been shown to be activated by IL-4 and produce IL-4, IL-5, IL-10 and IL-13
  • Th17 cells, a more recently identified Th cell subset that has altered the classic Th1/Th2 paradigm, produce IL-17 A/F, IL-21, and IL-22. IL-1, IL-6, IL-23, and TGF-β are now known to play important roles in the differentiation and propagation of the Th17 cell lineage
  • there is an overall notion that pro-inflammatory Th1 and Th17 associated cytokines are elevated during the early stages of scleroderma, whereas Th2 cytokines mainly correlate with disease damage and fibrosis extent
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    morphea
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