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31.
B. P. Imbimbo T. Mant M. Edwards D. Amin N. Dalton F. Boutignon V. Lenaerts P. Wüthrich R. Deghenghi 《European journal of clinical pharmacology》1994,46(5):421-425
Hexarelin is a new hexapeptide (His-d-2-methyl-Trp-Ala-Trp-d-Phe-Lys-NH2) that stimulates the release of growth hormone both in vitro and in vivo. In this double-blind, placebo-controlled, rising-dose study we evaluated the growth hormone releasing activity of hexarelin in healthy human subjects. Twelve adult male volunteers received single intravenous boluses of 0.5, 1 and 2 ·g·kg–1 hexarelin as well as placebo. For safety, drug doses were given in a rising-dose fashion with placebo randomly inserted into the sequence. Plasma growth hormone concentrations increased dose-dependently after the injection of the peptide, peaking at about 30 min and then decreasing to baseline values within 240 min with a half-life of about 55 min. The mean peak plasma growth hormone concentrations (Cmax) were 3.9, 26.9, 52.3, 55.0 ng·ml–1 after 0, 0.5, 1 and 2 g·kg–1, respectively. The corresponding areas under the curve of growth hormone plasma levels from drug injection to 180 min (AUC0–180) were 0.135, 1.412, 2.918 and 3.695 g·min·ml–1. The theoretical maximum response (Emax) and the dose that produces half of the maximum response (ED50) were estimated using logistic regression. The calculated ED50 values were 0.50 and 0.64 g·kg–1 for Cmax and AUC0–180, respectively. The corresponding Emaxs were 55.1 ng·ml–1 and 3936 ng·min·ml–1, thus indicating that the effect after the 2 g·kg–1 dose is very close to the maximal response. Plasma glucose, luteinising hormone, follicle-stimulating hormone, thyroid-stimulating hormone and insulin-like growth factor I were unaffected by hexarelin administration, while the peptide caused a slight increase in prolactin, cortisol and adrenocorticotropic hormone levels. Hexarelin was well tolerated in all subjects. The results of this study indicate that intravenous administration of hexarelin in man produces a substantial and dose-dependent increase of growth hormone plasma concentrations. 相似文献
32.
Vasilios Tanos Shevach Friedler Asher Shushan Nurith Strauss Iftach Hetsroni Aby Lewin 《Journal of assisted reproduction and genetics》1995,12(10):715-719
Purpose
Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 g/daily in their first cycle and received
d-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their first cycle and received nafarelin in the second.Results
Estradiol suppression was achieved by both
d-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P=0.0005) and the length of administration of hMG required for ovarian stimulation (P=0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P=0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.Conclusion
Our results demonstrate that nafarelin acetate is comparable to
d-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with fewer ampoules of hMG, administered for a shorter period of time, thus with a lesser cost. 相似文献
33.
Richard J. Paulson Mark V. Sauer Rogerio A. Lobo 《Journal of assisted reproduction and genetics》1994,11(1):28-32
Purpose
To describe our preliminary experience with the addition of a GnRH antagonist (Nal-Glu) and exogenous gonadotropins (follicle stimulating hormone; FSH) to unstimulated IVF cycles.Method
Seven spontaneously ovulatory women underwent eight unstimulated IVF cycles at our institution. They were treated with a single dose of Nal-Glu, 50 g/ kg, or with a combination of Nal-Glu, 50 g/kg, and exogenous FSH, 150–300 IU, during the late follicular phase of spontaneous cycles. They then received 10,000 IU of human chorionic gonadotropin (hCG) to time accurately follicle aspiration in unstimulated IVF cycles.Results
Two women underwent three cycles with Nal-Glu alone on the day of hCG administration. One pregnancy resulted. Five women underwent five cycles with 3 to 6 days of daily Nal-Glu and FSH. Four of these cycles resulted in aspiration after the FSH dose was increased to 300 IU. Nal-Glu and FSH allowed continued development of the dominant follicle without the occurrence of luteinizing hormone (LH) surge.Conclusions
(1) Nal-Glu alone given 18 hr prior to hCG did not interfere with continued follicle viability or with the attainment of pregnancy. (2) Simultaneous Nal-Glu and FSH allowed for continued growth and development of the dominant follicle without the occurrence of an LH surge. (3) This preliminary experience confirms the feasibility of this novel approach, which may ultimately enhance the efficacy of unstimulated IVF cycles by eliminating premature ovulation and maximizing control of gonadotropin delivery to the developing follicle.Presented at the 39th Meeting of The Society for Gynecologic Investigation, San Antonio, Texas, March 18–21, 1992. 相似文献
34.
PIERRE-MARC BOULOUX SALVATORE CORSELLO MICHAEL BESSER ASHLEY GROSSMAN 《British journal of clinical pharmacology》1996,42(2):225-232
- Intravenous bolus doses of thyrotrophin releasing hormone (TRH, 50–1000 μg) caused statistically significant, non-dose dependent and transient rises in blood pressure, heart rate and plasma catecholamines in healthy young males.
- Mean peak incremental rises in systolic blood pressure (mean ± s.e. mean) following 50, 200 and 500 μg TRH were 14.3 ± 2.9 mmHg, 15.7 ± 3.2 mmHg and 17.1 ± 3.9 mmHg respectively (all P < 0.05 vs placebo). Mean incremental rises in heart rate for the three doses of TRH were 8.2 ± 2.2 beats min−1, 7.1 ± 1.8 beats min−1, and 1O.7 ± 2.9 beats min−1 respectively (all P < 0.05 vs placebo).
- Following the 50 μg and 1000 μg doses of TRH, plasma noradrenaline and adrenaline rose significantly (P < 0.05) between 4 and 8 min. Mean ± s.e. mean incremental plasma noradrenaline rise following 50, 200 and 1000 μg TRH were 0.4 ± O.13 nmol 1−1, 0.37 ± 0.21 nmol 1−1 and 0.41 ± 0.18 nmol 1−1 respectively. Mean ± s.e. mean incremental rise in adrenaline for the 50, 200 and 1000 μg dose were 0.13 ± 0.04 nmol 1−1, 0.08 ± 0.03 nmol 1−1, and 0.11 ± 0.05 nmol l−1 respectively.
- Following administration of the ganglion blocking drug pentolinium (5 mg) the incremental systolic blood pressure and heart rate rises following 500 μg TRH alone 16.6 ± 2.8 mmHg and 1O.4 ± 3.1 beats min−1 respectively.
- The rises in plasma noradrenaline and adrenaline following TRH were attenuated by prior ganglion blockade.
- α-adrenoceptor blockade with thymoxamine (0.3 mg kg−1 bolus + 0.3 mg kg−1 h−1 infusion), singly and combined with intravenous propranolol (10 mg i.v. over 10 min), did not alter the pressor or tachycardic effects of 500 μg TRH.
- In conclusion, although plasma noradrenaline rises following i.v. TRH, suggesting activation of the sympathetic nervous system, this effect is not responsible for the pressor response to TRH, which appears to be due to either a direct vasoconstrictive effect on the peripheral resistance vessels or a direct inotropic/chronotropic effect on the heart.
35.
Controlled trial of thyrotropin releasing hormone tartrate in ataxia of spinocerebellar degenerations 总被引:4,自引:0,他引:4
I Sobue T Takayanagi T Nakanishi T Tsubaki M Uono M Kinoshita A Igata M Miyazaki M Yoshida K Ando 《Journal of the neurological sciences》1983,61(2):235-248
The clinical efficacy, dose-response relationship, and safety of TRH-T (thyrotropin releasing hormone tartrate) were assessed in 290 patients with spinocerebellar degeneration (SCD) in a 2-week, double-blind study using placebo as control. 254 patients satisfied the criteria for inclusion in evaluation of the drug efficacy. The patients were treated with TRH-T in an intramuscular dose of 2 mg, 0.5 mg or 0 mg (placebo) as TRH once a day for 2 weeks. Clinical responses to these treatments were evaluated 3 times: at the end of weeks 1 and 2 of treatment and a week after the end of treatment. The results of "global improvement rating" as well as those of "ataxia improvement rating" showed that both 2 mg and 0.5 mg TRH-T treatments were significantly superior to placebo treatment in patients with predominantly cerebellar form of SCD. The effect was well maintained a week after the end of the 2-week treatment in the patients who were given TRH-T in daily dose of 2 mg and showed improvement at the end of treatment. The results of "improvement rating of each symptom" revealed that 2 mg treatment was significantly more effective than placebo for disorders of standing, gait, speech and writing. In the patients who had no pyramidal involvement or disorder of deep sensation, the drug efficacy and dose-response relationship were evident. Adverse reactions to the drug such as headache, feeling febrile and nausea were observed in 50% of the patients on 2 mg treatment, in 38% of those on 0.5 mg treatment and in 21% of those on placebo patient, however, discontinued treatment because of adverse reactions. 相似文献
36.
Treatment variables in relation to oocyte maturation: Lessons from a clinical micromanipulation-assisted in vitro fertilization program 总被引:1,自引:0,他引:1
Ori M. Avrech Gil A. Goldman Onit Rufas Anat Stein Shoshana Amit Israel Yoles Haim Pinkas Benjamin Fisch 《Journal of assisted reproduction and genetics》1997,14(6):337-342
Objective: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing
hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte-nuclear
maturity.
Design: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted
IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins.
Setting: The setting was the infertility and IVF unit of a tertiary academic medical center.
Participants: Two hundred twenty-one patients underwent 435 treatment cycles.
Main Outcome Measure: This was the proportion of germinal vesicle-intact immature (GVII) oocytes.
Results: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment
cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in
which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled
ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher
peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, >14 mm) and oocytes
retrieved.
Conclusions: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation
regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently
associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in
patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure
in some of these cases is due to oocyte, rather than sperm, dysfunction. 相似文献
37.
腹腔镜手术治疗中重度内膜异位症的术后用药 总被引:2,自引:0,他引:2
目的 探讨中重度内膜异位症腹腔镜手术治疗后 ,加用内分泌治疗的必要性以及副作用。方法 1 9位患者术后不用药 (A组 )、 1 9例加用人工合成孕激素治疗 (B组 ) ,1 8例促性腺激素释放激素激动剂(GnRH -a)治疗 (C组 ) ,比较三组患者术后复发、妊娠结局及用药副作用情况。结果 A组 1 5 8%复发 ,B组2 6 3%复发 ,C组 1 7 0 %复发 ,三组差异无显著性 (P >0 0 5 )。三组不孕患者妊娠情况差异无显著性 (P >0 0 5 )。B组 7例患者未完全闭经 ,C组全部闭经 ,B组及C组闭经时间分别为 (4 4 0± 2 3 7)d及 (4 0 0± 1 3 6 )d ,复潮时间分别为 (4 8 7± 2 6 6 )d及 (5 8 1± 1 7 4 )d ,两组间差异无显著性 (P >0 0 5 ) ,但B组患者闭经及复潮的发生更加不确定。B组患者以高雄激素症状为主 ,5例患者服药后声音变低钝 ,C组患者以低雌激素所至围绝经期征候为主 ,均于停药后恢复。结论 对于有生育要求的患者 ,手术者若能彻底地清除盆腔内膜异位病灶 ,术后可不用药。 6~ 1 2个月后未妊娠者 ,考虑用药及助孕治疗。孕激素类药物使用前应充分交代该药的副作用 ,特别注意特殊职业的患者 相似文献
38.
溴隐亭对高泌乳素血症妇女促性腺激素诱导排卵的影响 总被引:1,自引:0,他引:1
目的:探讨比较高泌乳素血症患者促排卵治疗中溴隐亭应用时机对诱导排卵的影响。方法:回顾性分析62例高泌乳素血症患者促卵泡激素药物促排卵治疗方式,分为A、B两组,A组:溴隐亭与促排卵药物治疗同时进行。B组:溴隐亭治疗高泌乳素血症后促排卵治疗。结果:两组治疗方案,A组促排卵治疗用药量、用药时间明显增加,妊娠率低,流产率高,促排卵周期雌二醇水平较B组低;B组方案促排卵率高、妊娠率高,流产率低。结论:溴隐亭治疗高泌乳素血症后,使用促卵泡激素药物促排卵治疗不育疗效显著。 相似文献
39.
40.
目的制备用于治疗溃疡性结肠炎的pH依赖型愈肠宁结肠靶向片(pH-dependen t Y uchangn ing T ab let forco lon-spec ific de livery,PYTCSD),并对其体内外释放性能进行评价,探讨制备中药结肠靶向制剂的可行性。方法以苦参碱和氧化苦参碱体外释放度为指标,对制剂的包衣处方进行筛选;采用体外释放度测定法考察该制剂的体外释放性能;采用硫酸钡造影技术对该制剂在人体内的释放性能进行评价。结果拟订了PYTCSD的制备方法:将药物制备得片芯后,以质量浓度3.70%(g/mL)丙烯酸树脂Ⅲ(Eudrag itⅢ)、0.37%(g/mL)邻苯二甲酸二乙酯(DEP)、0.93%(g/mL)滑石粉的乙醇混悬溶液为包衣液,包衣使片芯增重8%,即得;体外释放度测定结果表明,在人工胃液2 h时溶出液中未检测到苦参碱和氧化苦参碱,在人工小肠液4 h时两指标累积溶出率均<10%,而在人工结肠液1 h时苦参碱和氧化苦参碱分别累积溶出86.5%和86.8%;体内释放度试验结果表明,PYTCSD在8名志愿者体内均能完整到达回盲部或升结肠,并在上述部位崩解释放出药物。结论制备得pH依赖型愈肠宁结肠靶向片能达到较好结肠定位释药的目的。 相似文献