49 research outputs found
Эффективность и безопасность подкожных имплантатов гистрелина у пациентов с распространенным раком предстательной железы
Проанализированы результаты исследований эффективности и переносимости препарата Вантас «Орион» (подкожный имплантат, содержащий 50 мг гистрелина ацетата) при распространенном раке предстательной железы (III–IV ст.). Ключевые слова:
рак предстательной
железы, гормональная
терапия, агонисты ГнРГ,
гистрелина ацетат,
Вантас, эффективность,
переносимость.The results of Histrelin Study Group investigation of efficacy and safety of Vantas «Orion» (subdermal implant of 50 mg of histrelin acetate) in men with advanced prostate cancer (III–IV st.) are analized. Key Words: prostate cancer, hormone therapy, agonists
GnRH, histrelin acetate, Vantas, efficacy, safety
Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.
PURPOSE: Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis.
MATERIALS AND METHODS: Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.
RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs.
CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men
An analysis of the FIR/RADIO Continuum Correlation in the Small Magellanic Cloud
The local correlation between far-infrared (FIR) emission and radio-continuum
(RC) emission for the Small Magellanic Cloud (SMC) is investigated over scales
from 3 kpc to 0.01 kpc. Here, we report good FIR/RC correlation down to ~15 pc.
The reciprocal slope of the FIR/RC emission correlation (RC/FIR) in the SMC is
shown to be greatest in the most active star forming regions with a power law
slope of ~1.14 indicating that the RC emission increases faster than the FIR
emission. The slope of the other regions and the SMC are much flatter and in
the range of 0.63-0.85. The slopes tend to follow the thermal fractions of the
regions which range from 0.5 to 0.95. The thermal fraction of the RC emission
alone can provide the expected FIR/RC correlation. The results are consistent
with a common source for ultraviolet (UV) photons heating dust and Cosmic Ray
electrons (CRe-s) diffusing away from the star forming regions. Since the CRe-s
appear to escape the SMC so readily, the results here may not provide support
for coupling between the local gas density and the magnetic field intensity.Comment: 19 pages, 7 Figure
Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1
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,261023), rare X-linked
CNVs by 29%, (OR 1.29 [1.11–1.50], p,161023), 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 = 6.261025). 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.This work was partially funded by the Portuguese Foundation for Science and Technology FCT/MCTES (PIDDAC) and co-financed by European funds (FEDER) through the COMPETE program, research grant PTDC/SAU-GMG/101229/2008. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT. AML is the recipient of a postdoctoral fellowship from FCT (SFRH/BPD/73366/2010). CO is supported by a grant from the United States National Institutes of Health (R01 HD21244), JDS is supported by Damon Runyon Clinical Investigator Award, Alex's Lemonade Stand Foundation Epidemiology Award, and the Eunice Kennedy Shriver Children's Health Research Career Development Award NICHD 5K12HD001410. Support for humans studies and specimens were provided by the NIH/NIDDK George M. O'Brien Center for Kidney Disease Kidney Translational Research Core (P30DK079333) grant to Washington University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Cosmological parameters from SDSS and WMAP
We measure cosmological parameters using the three-dimensional power spectrum
P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in
combination with WMAP and other data. Our results are consistent with a
``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt,
tensor modes or massive neutrinos. Adding SDSS information more than halves the
WMAP-only error bars on some parameters, tightening 1 sigma constraints on the
Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter
density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on
neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when
dropping prior assumptions about curvature, neutrinos, tensor modes and the
equation of state. Our results are in substantial agreement with the joint
analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive
consistency check with independent redshift survey data and analysis
techniques. In this paper, we place particular emphasis on clarifying the
physical origin of the constraints, i.e., what we do and do not know when using
different data sets and prior assumptions. For instance, dropping the
assumption that space is perfectly flat, the WMAP-only constraint on the
measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to
t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running
tilt, neutrino mass and equation of state in the list of free parameters, many
constraints are still quite weak, but future cosmological measurements from
SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt
figures available at http://www.hep.upenn.edu/~max/sdsspars.htm
Status of the CCD development for the Dark Energy Spectroscopic Instrument
We describe improvements in CCD performance that have been achieved on 4k×4k, (15 μm)2-pixel, fully depleted CCDs for the Dark Energy Spectroscopic Instrument (DESI) [1]. With respect to our previous work on CCDs for the Dark Energy Camera and the Baryon Oscillation Spectroscopic Survey, our goals for the DESI CCD development were to improve read noise and quantum efficiency, improve the astrometric precision, and decrease pixel-size variations. We report experimental results on recently fabricated CCDs to be used in DESI
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