Stress-induced insomnia: opioid-dopamine interactions

REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour.     

In vitro activity of Tridax procumbens against promastigotes of Leishmania mexicana

Ethnopharmacological relevance

Tridax procumbens is an active herb against leishmaniasis.

Aim of the study

Leishmaniasis is a group of diseases caused by Leishmania protozoa. We investigated the antileishmanial activity of Tridax procumbens extracts and a pure compound against promastigotes of Leishmania mexicana, the causative agent of cutaneous leishmaniasis in the New World.

Materials and methods

Extracts and (3S)-16,17-didehydrofalcarinol (1) were obtained by chromatographic methods from Tridax procumbens, and the latter identified by spectroscopic analysis. The effect of these extracts and 1 on the growth inhibition of promastigotes of Leishmania mexicana was evaluated. In order to test the safety of extracts and 1, mammalian cells were treated with them, and cell viability was assessed using trypan blue and MTT.

Results

We demonstrated that extracts of Tridax procumbens and 1 showed a pronounced activity against Leishmania mexicana. The methanol extract inhibited promastigotes growth of Leishmania mexicana with a 50% inhibitory concentration (IC₅₀) of 3 μg/ml, while oxylipin 1 exhibited the highest inhibition at IC₅₀ = 0.478 μg/ml.

Conclusions

In this study we report the biological activity of extracts and (3S)-16,17-didehydrofalcarinol (1), obtained from Tridax procumbens, on the promastigote form of Leishmania mexicana, with no effect upon mammalian cells.     

Revealing the enigmas of implantation: what is the true impact of ovarian hyperstimulation?

It is agreed that ovarian stimulation results in histopathologic changes and variations in gene expression when compared to natural cycles. However, the enigma is still present: What is the true impact of variable degrees of embryo-endometrium developmental asynchrony in the presence of high clinical embryo implantation rates in IVF? It is postulated that the temporal characterization of gene expression and protein profiles of isolated endometrial compartments might unveil patterns that are critical for the establishment of the window of implantation.     

Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection

OBJECTIVE: To investigate the effect of continuous administration of gonadotropin-releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program. STUDY DESIGN: One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer-generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration. RESULTS: Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference. CONCLUSION: Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles.     

Cumulative exposure to high estradiol levels during the follicular phase of IVF cycles negatively affects implantation

Purpose: To investigate the effect of the cumulative exposure to estradiol (E₂) during the follicular phase on IVF outcome. Methods: Patients were stimulated with recombinant FSH after GnRH agonist suppression and had a day 3-embryo transfer. Estrogen exposure was determined as the area under the curve (AUC) for serum E₂ levels measured from the first day of stimulation through the day after hCG administration. Results: E₂ AUC thresholds for 10th and 90th percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and implantation rates were highest in the 10th–90th percentile group, and were statistically higher in this group than in the >90th percentile group (54.6% vs. 33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P < 0.05). Recovered mature oocytes, fertilization, and number and mean score of transferred embryos were similar. Conclusions: High cumulative E₂ exposure during the follicular phase of IVF cycles has detrimental effects on implantation.     

Current status of robotically assisted laparoscopic surgery in reproductive medicine and gynaecology

Laparoscopic techniques have revolutionized the concept of minimally invasive surgery. Robotically assisted surgery is one of the latest innovations in this field and many operative laparoscopic procedures have been performed in urology, cardiac and general surgery. More recently, the use of robotically assisted techniques have been introduced in gynaecology, and most available studies have shown it to be a safe and effective alternative to conventional laparoscopic surgery. However, whether or not to approach the management of certain gynaecological pathologies with a laparotomy or laparoscopy (conventional or with robotic aid) continues to be a point of debate. This article reviews recent developments in the endoscopic management of reproductive (tubal reanastomosis and myomectomies) and other gynaecological surgical conditions (hysterectomies, pelvic organ prolapse, repair of vesicovaginal fistulas and staging for gynaecological malignancies). Ongoing controversies associated with this technology, such as cost, learning curve, conversion rate to laparotomy, post-surgical fertility and complications, are briefly addressed. Long-term analysis of outcomes is ongoing.     

HOXD8 hypermethylation as a fully sensitive and specific biomarker for biliary tract cancer detectable in tissue and bile samples

Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer