ABSTRACT
High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/1 on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.
ABSTRACT
High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open-label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/l on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist.
Subject(s)
Gonadotropin-Releasing Hormone/antagonists & inhibitors , Luteinizing Hormone/therapeutic use , Ovulation Induction , Recombinant Proteins/therapeutic use , Adult , Dose-Response Relationship, Drug , Female , Humans , Luteinizing Hormone/genetics , Prospective Studies , Recombinant Proteins/geneticsABSTRACT
At the onset of West syndrome a specific impairment of visual function has been clearly demonstrated, while other aspects of sensorial development, and in particular of the auditory function, have been less studied. The aim of this study was to evaluate auditory function and orienting responses at the onset of West syndrome, and to relate the results with EEG patterns, visual function and neurodevelopmental competence. A prospective multicentric study was performed on 25 successively enrolled infants with West syndrome; all the patients underwent a full clinical assessment, including MRI and video-EEG, visual function and auditory orienting responses (AORs) as well as Griffiths' developmental scales. The whole assessment performed at the onset of spasms (T0) was repeated after two months (T1). AORs resulted significantly impaired both at T0 and T1. At the onset of spasms a highly significant relationship of auditory attention with visual function and neurodevelopmental competence was shown in both cryptogenic and symptomatic forms, but it was no longer present after two months. Our results may suggest a possible pervasive effect of the epileptic disorder on sensory processing, associated to a deficit of neurodevelopment. Although we failed to show a significant correlation between auditory orienting responses and EEG patterns, some evidence seems to support at least partially an influence of the epileptic disorder per se on the genesis of the sensorial impairment. A longer follow up and a larger cohort will be useful for a better clarification of these findings.
Subject(s)
Attention/physiology , Electroencephalography , Hearing/physiology , Spasms, Infantile/physiopathology , Vision, Ocular/physiology , Acoustic Stimulation/methods , Female , Humans , Infant , Magnetic Resonance Imaging/methods , Male , Retrospective StudiesABSTRACT
Two new steroidal glycosides, 3beta-O-(3'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein A, 2) and 3beta-O-(4'-O-acetyl-beta-D-arabinopyranosyl)-25xi-choles tan e-3beta, 5alpha,6beta,26-tetrol-26-acetate (riisein B, 3), were isolated from extracts of the Brazilian telestacean octocoral Carijoa (Telesto) riisei collected near Rio de Janeiro. The new glycosides co-occur with the polyhydroxy sterol, 25xi-cholestane-3beta,5alpha,6beta, 26-tetrol-26-acetate (1), an inseparable diastereomeric mixture previously reported from Telesto riisei collected in Micronesia. The structures of the new glycosides were assigned by spectroscopic methods and by comparison with spectral data for sterol 1. Riiseins A and B showed in vitro cytotoxicity toward HCT-116 human colon adenocarcinoma with IC(50) values of 2.0 microg/mL.
Subject(s)
Antineoplastic Agents/isolation & purification , Cnidaria/chemistry , Glycosides/isolation & purification , Sterols/isolation & purification , Animals , Antineoplastic Agents/chemistry , Glycosides/chemistry , Magnetic Resonance Spectroscopy , Sterols/chemistryABSTRACT
The structures of two new, naturally occurring cytotoxic depsipeptides, tamandarins A and B (1 and 2), are presented. The tamandarins were isolated from an unidentified Brazilian marine ascidian of the family Didemnidae. The structures of the new cytotoxins were assigned by interpretation of FABMS data and by extensive 2D NMR analyses. The absolute configurations of the tamandarins were assigned by acid and alkaline hydrolysis to yield their corresponding amino acids, which were then analyzed as their Marfey derivatives. The cytotoxicity of tamandarin A (1) was evaluated against various human cancer cell lines and shown to be slightly more potent than didemnin B. A qualitative discussion of the conformation of tamandarin A (1) in solution, obtained from NMR J-value data, variable temperature experiments, and NOESY/ROESY data, is included.