Abstract:
:Estrogens are represented by a diverse group of compounds. Within this large family of molecules are tissue-selective estrogens that have been classified as selective estrogen receptor modulators (SERMs). These compounds are characterized by the fact that they exhibit both estrogen agonist and antagonist activity dependent upon the gene promoter and target tissue being examined. SERMs have been intensively studied over the past decade, especially since one, raloxifene, has been approved for the prevention and treatment of postmenopausal osteoporosis. While not a replacement for hormone replacement therapy (HRT), raloxifene can be an alternative to it and other treatments for osteoporosis. The ideal SERM would provide the positive benefits associated with HRT without the uterine and breast stimulation. Raloxifene does achieve some of the benefits of HRT, specifically on the skeleton and lipid metabolism with no apparent uterine effects, and a potential decreased risk of developing breast cancer associated with raloxifene therapy. However, there are a number of parameters that can be improved. A number of SERMs have been evaluated only to fail in development due to, for the most part, uterine safety issues. In order to develop an improved SERM, a stringent screening process was designed to select compounds that did not stimulate the uterus or breast. At the same time, these new compounds would have a positive impact on the skeleton and lipid metabolism with the additional improvement (over raloxifene) of a neutral effect on hot flashes. Under these strict conditions, WAY-140424 was developed and, to date, the preclinical pharmacology data have accurately predicted the clinical response demonstrated in phase I and II trials.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Komm BS,Lyttle CRdoi
10.1111/j.1749-6632.2001.tb04039.xsubject
Has Abstractpub_date
2001-12-01 00:00:00pages
317-26eissn
0077-8923issn
1749-6632journal_volume
949pub_type
杂志文章,评审abstract::The term intrauterine growth restriction (IUGR) is assigned to newborns with a birth weight and/or birth length below the 10th percentile for their gestational age and whose abdominal circumference is below the 2.5th percentile with pathologic restriction of fetal growth. IUGR is usually due to maternal, fetal, or pla...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1365.012
更新日期:2006-12-01 00:00:00
abstract::Abnormal function of the lymphatic vessels is associated with a variety of diseases, such as tumor metastasis and lymphedema. The development of strategies for local and controlled induction or inhibition of lymphangiogenesis would thus be of major importance for the treatment of such diseases. Two growth factors, vas...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2002.tb04871.x
更新日期:2002-12-01 00:00:00
abstract::The discovery of AQP4-IgG (a pathogenic antibody that targets the astrocytic water channel aquaporin-4), as the first sensitive and specific biomarker for any inflammatory central nervous system demyelinating disease (IDD), has shifted emphasis from the oligodendrocyte and myelin to the astrocyte as a central immunopa...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.12794
更新日期:2016-02-01 00:00:00
abstract::Hantaviruses belong to the Bunyaviridae family. While usually hosted by wild mammals, they are potentially pathogenic for humans, and several serologically distinct groups associated with different syndromes have been identified. Yet, investigations have mostly been conducted where human infections by hantaviruses con...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1428.064
更新日期:2008-12-01 00:00:00
abstract::The dynamics and kinematics of saccades in a patient with severe ocular myasthenia were studied before and after treatment with intravenous immunoglobulin (IVIG). Before therapy, horizontal saccades were hypometric, but faster than similar-sized saccades made by normal subjects. During a 5-minute test period, saccades...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2008.03712.x
更新日期:2009-05-01 00:00:00
abstract::The molecular biological approach has provided important information toward understanding the complexities of the F0F1 ATPase. This article focuses on our recent results on the ATPase catalytic site contained in the beta subunit and the role of the gamma subunit in regulation of proton transport. We used a combination...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1992.tb43807.x
更新日期:1992-11-30 00:00:00
abstract::Calcium-dependent activator protein for secretion (CAPS) was initially identified in brain cytosol based on its ability to reconstitute calcium-triggered dense-core vesicle (DCV) exocytosis in permeable cell lines (PC12) of adrenal chromaffin origin. Current evidence indicates that CAPS functions selectively in DCV ex...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2002.tb04464.x
更新日期:2002-10-01 00:00:00
abstract::Reducing emissions from deforestation and forest degradation (REDD+) provides financial compensation to land owners who avoid converting standing forests to other land uses. In this paper, we review the main opportunities and challenges for REDD+ implementation, including expectations for REDD+ to deliver on multiple ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2011.06306.x
更新日期:2012-02-01 00:00:00
abstract::The DNase activity and circulating DNA (cirDNA) concentration in blood plasma of healthy donors, patients with chronic prostatitis, and patients with prostate tumors were analyzed. The concentration of the cirDNA from plasma was determined by PicoGreen fluorescent assay. DNase activity in blood was measured using the ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1448.016
更新日期:2008-08-01 00:00:00
abstract::As part of an ongoing randomized clinical trial for childhood-abuse-related PTSD, this study examined the association between PTSD and unresolved attachment as measured by the Adult Attachment Interview in a sample of 52 female childhood-abuse survivors. Results revealed that 55% of the sample was classified as preocc...
journal_title:Annals of the New York Academy of Sciences
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1196/annals.1301.036
更新日期:2003-12-01 00:00:00
abstract::Semi-conservative replication ensures that the DNA sequence of sister chromatids is identical except for replication errors and variation in the length of telomere repeats resulting from replicative losses and variable end processing. What happens with the various epigenetic marks during DNA replication is less clear....
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2012.06505.x
更新日期:2012-08-01 00:00:00
abstract::Brazilian spotted fever (BSF) is a highly lethal disease caused by Rickettsia rickettsii. In the present study, rickettsial infection was evaluated in 669 Amblyomma aureolatum adult ticks collected from naturally infested dogs in Taiaçupeba, a BSF-endemic area in the state of São Paulo. Ten (1.49%) ticks were infected...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1374.103
更新日期:2006-10-01 00:00:00
abstract::Starling's law and the end-systolic pressure-volume relationship (ESPVR) reflect the effect of sarcomere length (SL) on the development of stress (sigma) and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1420.010
更新日期:2008-03-01 00:00:00
abstract::Gastrointestinal peptides play important roles regulating feeding and energy homeostasis. Most gastrointestinal peptides including glucagon like peptide-1, peptide YY, amylin, and oxytomodulin are anorectic, and only ghrelin is an orexigenic peptide. Ghrelin increases appetite, modulates energy balance, suppresses inf...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2010.05509.x
更新日期:2010-07-01 00:00:00
abstract::Schizophrenia is a major mental disorder associated with core neurocognitive impairments. The ability to recreate these deficits in animal models is limited, hampering ongoing translational drug development efforts. This paper reviews the use of electroencephalography (EEG)-based neurophysiological measures, such as e...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.12689
更新日期:2015-05-01 00:00:00
abstract::Three patients with the clinical diagnosis of Wallenberg's syndrome caused by acute unilateral ischemic infarctions, which included the vestibular nucleus in the medullary brain stem and afferent vestibular pathways, were examined by positron emission tomography (PET) during caloric vestibular stimulation. They all ha...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1325.035
更新日期:2005-04-01 00:00:00
abstract::According to a current paradigm cardiovascular diseases can be initiated by exposure of vascular cells to qualitatively modified low-density lipoproteins (LDL). Capillary leakage, an early feature of diabetic retinopathy, results in the exposure of retinal pericytes to modified LDL, including glycated (G-LDL) and heav...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1333.045
更新日期:2005-06-01 00:00:00
abstract::Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1320.012
更新日期:2004-11-01 00:00:00
abstract::Colorectal cancer is the third most frequent fatal malignant neoplasm in the United States and is expected to cause significant morbidity and mortality. The recent recall of cyclooxygenase-2 inhibitors from clinical trials highlights the need to develop other agents for cancer chemoprevention trials. Intervention stra...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1196/annals.1339.016
更新日期:2005-11-01 00:00:00
abstract::Natural systems harbor complex interactions that are fundamental parts of ecology and evolution. These interactions challenge our inclinations and training to seek the simplest explanations of patterns in nature. Not least is the likelihood that some complex processes might be missed when their patterns look similar t...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/nyas.12974
更新日期:2015-12-01 00:00:00
abstract::The authors report their experience in the surgical treatment of bone deformities in osteogenesis imperfecta, based upon 45 operations in 13 severely affected patients. Three different procedures were used. Fragmentation and temporary fixation by means of a wire does not guarantee a sufficient protection of the bone a...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1988.tb55330.x
更新日期:1988-01-01 00:00:00
abstract::The arterial baroreflex has two important functions. First, the arterial baroreflex is a negative feedback reflex that regulates arterial pressure around a preset value called a set or operating point. Second, the arterial baroreflex also establishes the prevailing systemic arterial pressure when the operating point i...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.2001.tb03688.x
更新日期:2001-06-01 00:00:00
abstract::We conducted an experimental study of the interaction and coalescence of two drops (of the same fluid) or bubbles translating under the action of buoyancy in a cylindrical tube. The close approach of two Newtonian fluid particles of different size in a non-Newtonian continuous phase was examined using image analysis, ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04092.x
更新日期:2009-04-01 00:00:00
abstract::Citizen soldiers (National Guard and Reserves) represent approximately 40% of the two million armed forces deployed to Afghanistan and Iraq. Twenty-five to forty percent of them develop PTSD, clinical depression, sleep disturbances, or suicidal thoughts. Upon returning home, many encounter additional stresses and hurd...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2010.05719.x
更新日期:2010-10-01 00:00:00
abstract::Cross-species hybridizations have enabled us to isolate and clone the gene for the beta chain of human fibrinogen. Highlights of the gene for the beta chain revealed by nucleotide sequence analyses, particularly in areas that have a direct bearing on defining the overall organization of the gene, have been presented. ...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1983.tb23265.x
更新日期:1983-06-27 00:00:00
abstract::The endocannabinoid system, through the cannabinoid receptor CB1, is involved in the modulation of adaptive responses to environmental conditions. However, little is known about the role of the cannabinergic system, particularly CB1 receptor expression, in relation to the effects induced by xenoestrogens concerning th...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.2009.04455.x
更新日期:2009-04-01 00:00:00
abstract::The theme of this presentation has been to show that the control of transmitter release at the neuromuscular synapse is achieved by extracellular and intracellular calcium. For the fast information transfer represented by the end-plate potential, the electrochemical gradient for calcium across the presynaptic membrane...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章,评审
doi:10.1111/j.1749-6632.1978.tb41983.x
更新日期:1978-04-28 00:00:00
abstract::Data on 3080 mother-infant pairs from Cebu in the Philippines were used to conduct a logistics hazards analysis to determine the effect of supplemental calories and the types of supplements that the infant ingests on return to menses. Breast feeding had a significant reduced odds of the mother returning to menses (od...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1994.tb30406.x
更新日期:1994-02-18 00:00:00
abstract::In this paper, I have introduced and solved a simple deterministic model of eye tracking that produces rich dynamical behavior. Some of its main features, notably the existence of a chaotic regime, are reminiscent of the anomalies reported in smooth pursuit eye tracking experiments with schizophrenia patients. By obta...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1111/j.1749-6632.1987.tb48737.x
更新日期:1987-01-01 00:00:00
abstract::Several recently published reports, including ours, suggest that adiponectin is a strong proinflammatory agent. Indeed, exposure of human placenta and adipose tissue to adiponectin induces the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and prostaglandin E2 (PGE2). We hav...
journal_title:Annals of the New York Academy of Sciences
pub_type: 杂志文章
doi:10.1196/annals.1367.013
更新日期:2006-11-01 00:00:00