In contrast to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists do not show any stimulatory effect on the pituitary but their clinical usage was precluded by severe side effects and high dose requirements. We report here on a 7-day treatment using the potent GnRH antagonist Cetrorelix ([Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10]GnRH) on five women 23-33 years old. All women were ovulatory and were studied during three consecutive cycles: a control cycle, a treatment cycle and a post-treatment control cycle. Throughout the control cycles blood samples were obtained daily during cycle days 8-18 and on days 21 and 23 during the remainder of the control cycles. On the eighth day of the treatment cycle women were hospitalized at 07.00 h for 26 h. Repeated blood samples were drawn at 15-min intervals during the entire period. Subjects received 3 mg of Cetrorelix sc for the first time at 09.00 h on the eighth day of the cycle and daily at 08.00 h for the following 6 days. Blood samples were obtained daily over a period of 25 days and every third day throughout the remainder of the treatment cycle. Twenty-four hours after the first application of Cetrorelix, luteinizing hormone (LH) and estradiol were in the subnormal range and remained subnormal until the end of medication. The suppressive effect of Cetrorelix compared to pretreatment values lasted at least 6 days for LH and FSH and 11 days after the last Cetrorelix injection for estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of terodiline on contractions induced in isolated rabbit detrusor by carbachol and potassium, and by electrical field stimulation were investigated. Terodiline relaxed preparations contracted by carbachol and potassium and, when added 15 min before stimulation, decreased the contractile responses to these agents in a concentration-dependent way. Terodiline more effectively inhibited carbachol than potassium induced contractions. The "pure" calcium antagonist nifedipine had the opposite effect. Both atropine and terodiline caused a parallell shift to the right of the concentration-response curve to carbachol. The maximum contractile tension and slope were not affected, suggesting a competitive antimuscarinic effect within the concentration range used. Atropine was approximately 750 times more potent than terodiline. The maximum inhibitory effect of atropine and the calcium antagonist nimodipine on the electrically induced response were 40 % and 69 %, respectively. Terodiline caused complete inhibition of the response, as also did a combination of nimodipine and atropine. -T h e results suggest that terodiline in low concentrations has mainly an antimuscarinic action. To this, a calcium antagonistic effect is added at higher concentrations. The two-fold action of the drug makes it an effective inhibitor of bladder contraction, and an interesting tool for investigations of bladder contractility. K e y words: Terodiline-antimuscarinic action-calcium antagonism-rabbit detrusor
Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24-27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1-32 amino acids of the alpha-subunit of human inhibin. The normal range for men was 0.79-3.1 U/l x 10(-3), the sensitivity of the assay was 0.1 U/l x 10(-3) (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45-3.20 U/l x 10(-3). During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20-1.86 U/l x 10(-3). Highest testosterone levels were observed in the morning (20.5-36.6 pmol/l), lowest concentrations were detected at night (7.35-12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation.2+ volunteers follow a clear diurnal rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)
The objective of this study was to examine the changes in basal plasma gonadotropin, α-subunit, sex steroid, and prolactin levels and the prolactin and luteinizing hormone (LH) secretion pattern before, during and 161 days after treatment with a depot preparation of D-Trp-6-GnRH in young men. Gonadotropins, α-subunit, sex steroids, and prolactin were measured in pooled plasma samples. Additionally, before treatment, several times during its course and on day 161 after treatment, blood samples were drawn for 8h every 15 min for prolactin and LH measurements. After initial stimulation of the pituitary, administration of a depot preparation of D-Trp-6-GnRH resulted in a constant decrease in gonadotropin and sex steroid concentrations with LH and testosterone concentrations remaining within the limits of prepubertal levels from days 16 to 48. α-Subunit concentrations (0.4 ± 0.09 IU/l; mean ± SE) increased after application of D-Trp-6-GnRH, and remained elevated until day 48. Basal prolactin levels (3.5 ± 0.25 μg/l) did not change significantly during treatment but afterwards increased consistently with maximal levels at day 141 (15.3 ± 3.8 μg/l); they had decreased at day 161 to 10.3 ± 1.8 μg/l which is significantly higher than before treatment (p < 0.05). On day 161, prolactin pulse amplitude was significantly higher than before and during treatment (p < 0.05), while no significant changes in pulse frequency occurred. No significant temporal coupling between LH and prolactin release could be detected. In conclusion, after administration of a depot preparation of D-Trp-6-GnRH to 6 young men, there was a rise in basal prolactin levels and prolactin pulse amplitude as a long-term side effect of treatment, with maximal levels at 141 days after application.
Zusammenfassung: Im hypoglykämischen Bereich ist die Genauigkeit von Geräten zur Selbstkontrolle der Blut-Glucosekonzentration bisher nicht systematisch untersucht worden. In der vorliegenden Arbeit wurde die Genauigkeit von 4 weitverbreiteten Geräten (Companion 2®, Reflolux S®, One Touch II®, Ac-cutrend®) mit Vollblutproben, die approximativ auf Werte von 35, 45 und 45 mg/dl eingestellt waren, untersucht. Dabei fielen deutliche Unterschiede der prozentualen Abweichung von den mit der Hexokinasemethode erhaltenen Vergleichswerten auf: Während die Meßgenauigkeit des Companion 2® und des Reflolux S® mit Abweichungen ( ± s) von 11,2% ± 13,8% (n = 98, Spannweite 22-59 mg/dl) bzw. 8,4% ± 7,4% (n = 239, Spannweite 20-71 mg/dl) über den gesamten Prüfbereich annähernd gleich blieb, verschlechterte sich diese beim Accutrend® (n = 107) von 6,9% ± 6,1% (bei Glucosekonzentration um 55 mg/dl) auf 29,4% ± 24,6% (bei Glucosekonzentration um 35 mg/dl). Der One Touch II® zeigte im gesamten Prüfbereich die stärksten Abweichungen (23,7% ± 11,2%, n = 148). Die Prüfung von Geräten zur Selbstkontrolle der Blut-Glucosekonzentration im hypoglykämischen Bereich zeigt zum Teil klinisch bedeutsame Abweichungen, die bei der Auswahl von Geräten in Betracht gezogen werden sollten.Summary: Up to now, the accuracy of devices for self-monitoring of blood glucose concentration (SMBG) has not been systematically studied in the hypoglycemic ränge. In the present study the accuracy of four widely used SMBG'devices (Companion 2®, Reflolux S® [in some countries Accu-Chek III], One Touch II®, Accutrend®) was checked using whole blood samples that were adjusted to glucose concentrations of approximately 35. 45 or 55 mg/dl. There were clear differences between the devices in their relative deviation from the values obtained with the hexokinase method used for comparison: Companion 2® and Reflolux S® exhibited the same relative deviation (x ± s) over the whole ränge of blood glucose concentrations tested (11.2% ± 13.8%, n = 98, ränge 22-59 mg/dl and 8.4%±7.4%, n = 239, ränge 20-71 mg/dl), respectively. Accutrend® (n = 107) clearly showed higher deviations in the lower ränge (29.4% ±24.6% at approximately 35 mg/dl) than in the higher ränge (6.9% ± 6.1% at approximately 55 mg/dl). One Touch II® showed the largest deviation in the study (23.7% ± 11.2%, n = 148). In conclusion, this evaluation of SMBG devices showed partially clinically important deviations from the comparison method in the hypoglycemic ränge. These deviations should be considered in the choice of devices for SMBG.
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