Search

1. The objective was to determine the ontogeny of stereoselective fluoxetine (FX) disposition in postnatal sheep from newborn to adulthood.2. Catheters were implanted in a carotid artery an...

Approximately 1/3 of newborns exposed antenatally to selective serotonin reuptake inhibitors (SSRIs) exhibit poor neonatal adaptation. Although several potential mechanisms have been proposed, the actual mechanism has not been elucidated. We investigated outcomes in neonatal lambs exposed prenatally or postnatally to fluoxetine (FX). Daily FX injections (50 mg) were given intravenously (i.v.) to five pregnant ewes via implanted catheters beginning at 131–132 days gestation (term = 147 days) for 2 weeks. In another group, lambs with implanted vascular catheters had sterile water (n = 9) or FX (1 mg/kg, n = 12) injected i.v. on ~postnatal day (PND) 4. Prenatal FX-exposed lambs (n = 7) were hyperactive during PND 4 to 14 and their heart rate variability (HRV) was significantly lower than in control lambs (n = 7) on PND 2. In contrast, arterial pressure, heart rate, electrocardiogram, arterial blood gases, pH, glucose, lactate, cortisol, and sleep–activity cycles were not altered following postnatal FX injection. This abnormal postnatal hyperactivity with antenatal FX exposure may reflect increased maturity in terms of locomotory activity. The results suggest that altered brain development may be involved in the poor neonatal adaptation in human infants exposed to FX in utero.

Objective To compare the clinical and endocrine response of cycles in which GnRH agonists (GnRH-a) were stopped with cycles in which the agonists were continued during coasting. Design Retrospective study of stimulation cycles using flare and luteal agonist protocols. Setting Academic. Patient(s) Fifty-nine IVF and intracytoplasmic sperm injection (ICSI) treatment cycles in 57 women, coasted for 3 or more days. Intervention(s) The GnRH-a were withdrawn when E 2 levels continued to increase during coasting. Main Outcome Measure(s) Hormone concentrations, ultrasound findings, cycle cancellation, ovarian hyperstimulation syndrome (OHSS), oocyte retrieval, fertilization, embryo transfer, and clinical pregnancy rates (PR). Result(s) In the GnRH-a withdrawn group E 2 levels decreased by 63% (18,043–6,656 pmol/L) without cycle cancellations or cases of severe OHSS. In the agonist continuation group, the spontaneous E 2 decrease was 29% (14,205–10,132 pmol/L) with cycle cancellation and severe OHSS rates of 9.5% (4/42) and 4.8% (2/42), respectively. Oocyte retrieval, fertilization, embryo transfer, and clinical PRs were not compromised by stopping the agonists. Variations in the dynamic responses of FSH, LH, anti-Mullerian hormone, P, and androstenedione (A) levels in these cycles are described. Conclusion(s) Withdrawal of GnRH-a during coasting interrupted increasing E 2 levels, prevented cycle cancellation, and mitigated the risk of OHSS in this high risk group without compromising oocyte retrieval, fertilization, embryo transfer, or PRs.

An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method was developed and validated for the quantification of serotonin (5-HT) in lamb plasma using [(2)d(4)]-serotonin ([(2)d(4)]-5-HT) as an internal standard. Charcoal-stripped human plasma was used as the blank matrix during validation, and 5-HT was quantitated using selected reaction monitoring. The UHPLC/MS/MS system consisted of an Agilent 1290 Infinity ultrahigh-performance liquid chromatograph coupled with an AB SCIEX QTRAP(®) 5500 hybrid linear ion trap triple quadrupole mass spectrometer. The method was validated for accuracy, precision, linearity, lower limit of quantification (LLOQ), selectivity, and other parameters. The LLOQ was 1.0 ng/mL, requiring 100 μL of sample. The method was applied to monitor the 5-HT levels in lamb plasma after the administration of fluoxetine. Tandem mass spectrometry cubed (MS(3)) experiments were also performed to investigate the fragmentation pattern of 5-HT and [(2)d(4)]-5-HT. A liquid chromatography-MS(3) (LC/MS(3)) method was developed, and the UHPLC/MS/MS and the LC/MS(3) methods were compared for performance.