Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

EndocrinologyHormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third-generation gonadotrophin-releasing hormone antagonist(Cetrorelix) was used during ovarian stimulation in 32 patientsundergoing assisted reproduction, in order to prevent the prematureluteinizing hormone (LH) surge. In all patients, ovarian stimulationwas carried out with two or three ampoules of human menopausalgonadotrophin (HMG), starting on day 2 of the menstrual cycle.In addition, 0.5 mg of Cetrorelix was administered daily fromday 6 of HMG treatment until the day of ovulation inductionby human chorionic gonadotrophin (HCG). A significant drop inplasma LH concentration was observed within a few hours of thefirst administration of Cetrorelix (P<0.005). Moreover, noLH surge was detected at any point in the treatment period inany of the 32 patients. A mean oestradiol concentration of 2122±935ng/1 was observed on the day of the HCG administration, indicatingnormal folliculogenesis. Like LH, progesterone concentrationalso dropped within a few hours of the first administrationof Cetrorelix (P< 0.005). A 0.5 mg daily dose of Cetrorelixprevented a premature LH surge in all the 32 patients treated.     

Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion.

The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher.     

An open,randomized single-centre study to compare the efficacy and convenience of follitropin beta administered by a pen device with follitropin alpha administered by a conventional syringe in women undergoing ovarian stimulation for IVF/ICSI

BACKGROUND: A pen device, similar to an insulin pen, has been recently marketed for the administration of follitropin beta in cartridges. A randomized controlled trial was performed to compare the efficacy and convenience of this pen device delivering follitropin beta with a conventional syringe delivering follitropin alpha. METHODS: A total of 200 patients needing IVF/ICSI treatment and willing to self-inject were enrolled in the study. All subjects had ovarian stimulation according to a long protocol and were randomized to the pen or the conventional syringe group during down-regulation by means of a computer-generated randomization list using random numbers. Patients were asked to fill in a daily local tolerance book after each injection. On the day of hCG the patients scored a Visual Analogue Scale (VAS) for pain and convenience. RESULTS: The average duration, total dose of recombinant FSH and number of cumulus oocyte complexes retrieved were 10.8/12.0 days (P = 0.001), 1880/2226 IU (P < 0.001) and 15.2/13.1 respectively in the pen device and conventional syringe groups; the presence of pain after the daily injection was significantly higher in the conventional syringe group (P = 0.027); the visual analogue scale score was similar for pain but significantly more convenient for the pen device (P < 0.001). The live birth rate per embryo transfer was 32.9 and 34.4% respectively in the pen device and conventional syringe groups. CONCLUSIONS: Self-injection with the pen device is safe and easy, more convenient and less painful for the patient, requires less FSH and shortens the treatment duration.     

Stimulus-secretion coupling: role of cyclic AMP, cyclic GMP and calcium in mediating enzyme (kallikrein) secretion in the submandibular gland.

1. The role of adenosine 3':5'-phosphate (cyclic AMP) and guanosine 3':5'-phosphate (cyclic GMP) as second messengers for the enzyme secretory response evoked by the autonomic neurotransmitters, noradrenaline and acetylcholine, is examined in this in vitro study on the guinea-pig submandibular gland. 2. Noradrenaline increased enzyme (kallikrein) secretion. The initial stimulation of enzyme release appeared to be dose-dependent. The time course of cumulative kallikrein secretion revealed a complex pattern. Isoprenaline and phenylephrine were almost as potent as noradrenaline in releasing kallikrein. Both propranolol and phentolamine were required to fully inhibit the noradrenaline-stimulated enzyme secretion. 3. The cumulative secretion of kallikrein evoked by acetylcholine was dose-dependent. The onset of secretion showed a significantly greater time-lag than that observed with noradrenaline. Atropine effectively blocked the release of kallikrein by acetylcholine. 4. Dibutyryl cyclic AMP stimulated enzyme secretion. Dibutyryl cyclic GMP caused an initial increase which was not maintained. 5. The cyclic nucleotide phosphodiesterase inhibitors, theophylline and papaverine, increased basal kallikrein secretion. The action of the cyclic phosphodiesterase inhibitors on the secretory response to noradrenaline, acetylcholine, dibutyryl cyclic AMP and dibutyryl cyclic GMP was complex. In general, the increase in enzyme release produced by the secretagogues was additively enhanced by both inhibitors. 6. Omission of calcium inhibited both acetylcholine and dibutyryl cyclic GMP stimulated kallikrein release, but to a lesser degree than that of noradrenaline and dibutyryl cyclic AMP. High concentrations of extracellular calcium (10 mM) appeared to enhance the action of acetylcholine. 7. Noradrenaline produced a rise in the intracellular level of cyclic AMP. The increase preceded the stimulated secretion of kallikrein. Of the various adrenergic agonists, noradrenaline and isoprenaline were the most potent, whereas phenylephrine was significantly less effective in raising basal cyclic AMP values. Acetylcholine was without effect, even in the presence of a cyclic phosphodiesterase inhibitor. 8. Acetylcholine and noradrenaline raised intracellular levels of cyclic GMP only when the tissue incubations were performed in the presence of a cyclic phosphodiesterase inhibitor. The increase in cyclic GMP produced by acetylcholine preceded enzyme secretion. 9. Morphological data substantiated the finding that the in vitro release of kallikrein evoked by the secretagogues was associated with the depletion of secretory granules and vacuolations in acinar cells of the gland slices. 10. The molecular mechanisms which control enzyme secretion in the exocrine submandibular gland are discussed. Models are presented for the role of transmitter-specific cyclic nucleotides and calcium in stimulus-secretion coupling.     

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.