Lower levels of inhibin A and pro-alphaC during the luteal phase after triggering oocyte maturation with a gonadotropin-releasing hormone agonist versus human chorionic gonadotropin

OBJECTIVE: To investigate the effect of triggering oocyte maturation with GnRH agonist on corpus luteum function by measuring luteal phase levels of inhibin A and pro-alphaC. DESIGN: Prospective randomized trial. SETTING: In vitro fertilization (IVF) program at a university hospital. PATIENT(S): Infertile women undergoing IVF-ET treatment. INTERVENTION(S): Controlled ovarian hyperstimulation with FSH and GnRH antagonist, triggering of final oocyte maturation with either hCG (n = 8) or GnRH agonist (n = 8), IVF-ET, and collection of blood samples every 2-3 days during the luteal phase. MEASUREMENTS AND MAIN RESULTS: Luteal phase serum levels of inhibin A and pro-alphaC, P, and E(2). RESULT(S): Levels of inhibin A, pro-alphaC, estrogen, and P were significantly lower from day 4 to day 14 after triggering final oocyte maturation by GnRH agonist compared with hCG. Maximal luteal serum inhibin A and pro-alphaC levels were 91.5 +/- 23.6 and 184.1 +/- 23.5 pg/mL in the GnRH agonist-treated women compared with 464.7 +/- 209.1 and 7,351.6 +/- 934.3 pg/mL in women treated with hCG. CONCLUSION(S): Triggering final oocyte maturation with GnRH agonist instead of hCG in IVF cycles dramatically decreases luteal levels of inhibins, reflecting significant inhibition of the corpus luteum function. This effect may explain, at least in part, the mechanism of ovarian hyperstimulation syndrome prevention by the use of GnRH agonist.     

Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high-performance liquid chromatography with ultraviolet,fluorescence and mass spectrometric detection

The disposition of the non-steroidal anti-inflammatory drug (NSAID) nabumetone after a single oral dose administration of nabumetone tablets to humans and minipigs was investigated. Nabumetone is a prodrug, which is metabolized in the organism to the principal pharmacodynamically active metabolite -- 6-methoxy-2-naphthylacetic acid (6-MNA), and some other minor metabolites (carbonyl group reduction products, O-desmethylation products and their conjugates with glucuronic and sulphuric acids). Standards of the above-mentioned metabolites were prepared using simple synthetic procedures and their structures were confirmed by NMR and mass spectrometry. A simple HPLC method for the simultaneous determination of nabumetone, 6-MNA and the other metabolites was developed, validated and used for xenobiochemical and pharmacokinetic studies in humans and minipigs and for distribution studies in minipigs. Naproxen was chosen as the internal standard (I.S.), both UV (for higher concentrations) and fluorescence detection (for very low concentrations) were used. The identity of the nabumetone metabolites in biological samples was confirmed using HPLC-MS experiments. Pharmacokinetics of nabumetone, 6-MNA and 6-HNA (6-hydroxy-2-naphthylacetic acid) in human and minipig plasma was evaluated and compared. The concentration levels of nabumetone metabolites in urine, bile and synovial fluid were also evaluated.     

Severe OHSS: yes, there is a strategy to prevent it!

Effective measures to prevent ovarian hyperstimulation syndrome (OHSS) remain controversial. It became almost 'common knowledge' that there is no strategy that may completely prevent OHSS. Extensive clinical experience (albeit not derived from prospective randomized studies) clearly documents the ability of a single administration of gonadotrophin-releasing hormone (GnRH) agonist to effectively trigger ovulation, while completely eliminating any threat of clinically significant OHSS. This strategy cannot be used if the pituitary is down-regulated (as is the case in most assisted reproductive cycles today), however, the newly-introduced GnRH antagonists open new opportunities for implementing this strategy, since the pituitary preserves its responsiveness to GnRH agonists. Combining GnRH antagonist-based ovarian stimulation (particularly in 'high responders'), with GnRH agonist-driven ovulation triggering will make severe OHSS a disease of the past in assisted reproduction.     

Middle School Student Intentions to Play with Peers with Disabilities in Physical Education: Using the Theory of Planned Behavior

The purpose of the study was to develop a scale measuring intentions of children without disabilities to play with a hypothetical peer with a physical disability in general physical education using the Theory of Planned Behavior (Ajzen Organizational Behavior and Human Decision Processes 50:179–211, 1991) and to provide evidence of reliability, content validity, and initial factor structure. A background questionnaire and a pilot version of the Children’s Intentions to Play with Peers with Disabilities in Middle-School Physical Education (CIPPD-MPE) were administered to a convenience sample of 250 middle school students. Content validity of CIPPD-MPE was established by seven content experts. Findings revealed four factors (behavioral beliefs, control beliefs, behavioral intention, and normative beliefs), which explained 58% of the variance. Internal consistency ranged between .65 and .92. All factors were significantly correlated with intention, indicating the potential of CIPPD-MPE to predict intention of children without disabilities to play with a hypothetical peer with a physical disability in GPE.     

Trends and developments in radioprotection: the effect of nicotinamide on DNA repair

Recent studies point to the naturally occurring molecules in expression of radiation damage and in protection. DNA repair was shown to be one of the parameters that can be modified to attain improved protection. The need for a natural compound that can enhance DNA repair in order to improve cellular protection focused our attention on nicotinamide (NA). The effects of addition of NA, a precursor for NAD+ synthesis, on the DNA repair capacity following gamma and ultraviolet irradiations were studied in several repair-proficient and repair-deficient cell lines. The addition of low concentrations of NA (less than 3 mM) resulted in increased repair synthesis in the repair-proficient cells. Addition to repair-deficient cells resulted in decreased repair synthesis. Cells which repair damage from one type of radiation, and not from another, responded accordingly to the presence of NA. However, addition of high concentrations of NA to repair-proficient cells resulted in decreased repair synthesis. Thus, nicotinamide can improve the repair capacity in a concentration-dependent manner, but it clearly requires the existence of functional repair processes.     

Complexes of dihydroquercetin with chromium (III) and zinc (II) asparaginates in water and their effects on the state of lecithin membranes

The formation of chelate complexes of dihydroqercetin (DHQ) with zinc and chromium asparaginates in aqueous solution is established and their interaction with a lecithin monolayer is estimated. On the basis of analysis of the surface pressure-molecular area isotherms, it is concluded that an increase in the molecular area from 0.54 to 0.80–0.90 nm 2 is indicative of the immobilization of DHQ complexes in the lecithin monolayer. It is shown that the concentration of the initial products of lipid peroxidacion-diene and triene conjugates-decreases to 24 % and 41 %, respectively, and that of the final products (Schiff bases) in the blood of patients treated by Oftalvit (containing DHQ and metal asparaginates) decreases to 46 % in comparison to values in the control groups. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 10, pp. 14–20, October, 2008.     

High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health,Aging, and Disease

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Increasing the safety-promoting behaviors of abused women

OVERVIEW: Despite an epidemic of intimate-partner violence against women, and general agreement that women should be screened for it, few assessment and intervention protocols have been evaluated in controlled studies. To test a telephone intervention intended to increase the "safety-promoting behavior" of abused women, 75 women received six telephone calls over a period of eight weeks in which safety-promoting behaviors were discussed. A control group of 75 women received usual care. Women in both groups received follow-up calls to assess safety-promoting behaviors at three, six, 12, and 18 months after intake. Analysis showed that the women in the intervention group practiced significantly (P < 0.01) more safety-promoting behaviors than women in the control group at each assessment. On average, women in the intervention group practiced almost two more safety-promoting behaviors than they had at time of intake and nearly two more than women in the control group; the additional behaviors were practiced for 18 months. This nursing intervention requires only 54 minutes to complete (six nine-minute telephone calls) and can be integrated into any health care setting. Because less than one hour of professional nursing time is involved, the cost of the intervention is minimal. Future research should determine whether the adoption of safety-promoting behaviors by abused women averts trauma and its subsequent health care costs.     

Modulating cell adhesion to polybutylene succinate biotextile constructs for tissue engineering applications

Textile‐based technologies are powerful routes for the production of three‐dimensional porous architectures for tissue engineering applications because of their feasibility and possibility for scaling‐up. Herein, the use of knitting technology to produce polybutylene succinate fibre‐based porous architectures is described. Furthermore, different treatments have been applied to functionalize the surface of the scaffolds developed: sodium hydroxide etching, ultraviolet radiation exposure in an ozone atmosphere and grafting (acrylic acid, vinyl phosphonic acid and vinyl sulphonic acid) after oxygen plasma activation as a way to tailor cell adhesion. A possible effect of the applied treatments on the bulk properties of the textile scaffolds has been considered and thus tensile tests in dry and hydrated states were also carried out. The microscopy results indicated that the surface morphology and roughness were affected by the applied treatments. The X‐ray photoelectron spectroscopy and contact angle measurements showed the incorporation of oxygen‐containing groups and higher surface free energy as result of the surface treatments applied. The DNA quantification and scanning electron microscopy analysis revealed that these modifications enhanced cell adhesion and altered cell morphology. Generally, sodium hydroxide treatment altered most significantly the surface properties, which in turn resulted in a high number of cells adherent to these surfaces. Based on the results obtained, the proposed surface treatments are appropriate to modify polybutylene succinate knitting scaffolds, influencing cell adhesion and its potential for use in tissue engineering applications. Copyright © 2016 John Wiley & Sons, Ltd.     

BDNF Val66Met Impairs Fluoxetine-Induced Enhancement of Adult Hippocampus Plasticity

Recently, a single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene (BDNF Val66Met) has been linked to the development of multiple forms of neuropsychiatric illness. This SNP, when genetically introduced into mice, recapitulates core phenotypes identified in human BDNF Val66Met carriers. In mice, this SNP also leads to elevated expression of anxiety-like behaviors that are not rescued with the prototypic selective serotonin reuptake inhibitor (SSRI), fluoxetine. A prominent hypothesis is that SSRI-induced augmentation of BDNF protein expression and the beneficial trophic effects of BDNF on neural plasticity are critical components for drug response. Thus, these mice represent a potential model to study the biological mechanism underlying treatment-resistant forms of affective disorders. To test whether the BDNF Val66Met SNP alters SSRI-induced changes in neural plasticity, we used wild-type (BDNF^Val/Val) mice, and mice homozygous for the BDNF Val66Met SNP (BDNF^Met/Met). We assessed hippocampal BDNF protein levels, survival rates of adult born cells, and synaptic plasticity (long-term potentiation, LTP) in the dentate gyrus either with or without chronic (28-day) fluoxetine treatment. BDNF^Met/Met mice had decreased basal BDNF protein levels in the hippocampus that did not significantly increase following fluoxetine treatment. BDNF^Met/Met mice had impaired survival of newly born cells and LTP in the dentate gyrus; the LTP effects remained blunted following fluoxetine treatment. The observed effects of the BDNF Val66Met SNP on hippocampal BDNF expression and synaptic plasticity provide a possible mechanistic basis by which this common BDNF SNP may impair efficacy of SSRI drug treatment.