生长激素治疗中后期性早熟的临床评价

目的 观察生长激素（GH）对中后期性早熟患儿的最终成年身高的影响。方法 将12例性早熟（ICPP）患儿随机分A、B两组，A组联合使用促性腺激素释放类似物（GnRHa）与GH，B组单用GnRHa，并作对照，比较治疗前后骨龄（BA）、身高（HT）、预测成年身高（PAH）及第二性征的发育、血黄体生成素（LH）、卵泡刺激素（FSH）的变化。结果 A组身高增长大于B组（P〈0．05），A组PAH由149cm增加到158cm，B组PAH由150cm增加到153．5cm．两组治疗前后骨龄无显著变化。结论 联合使用GnRHa及GH对中后期ICPP患儿更有益提高身高。     

GnRHa与rhGH联合治疗大骨龄女性特发性性早熟疗效观察

目的观察单用促性腺激素释放激素类似物（GnRHa）和联合重组人生长激素（rhGH）应用对大骨龄女性特发性中枢性性早熟儿童生长速率与预测成年身高的影响。方法因月经初潮来本院儿科门诊就诊的特发性中枢性性早熟儿童均给予GnRHa治疗半年,半年后联合应用rhGH治疗。结果治疗3、6个月时,年化生长速率有所下降,应用生长激素治疗后,治疗9、12个月时年化生长速率明显增加（P〈0．01）;治疗前及治疗3、6、9、12个月时预测成年身高逐渐增高,尤其是应用rhGH治疗后,预测成年身高大幅度提高（P〈0．01）;治疗前及治疗3、6、9、12个月时平均骨龄差异无统计学意义（P〉0．05）。结论GnRHa联合应用rhGH能够显著提高患儿生长速率,改善预测身高。     

曲普瑞林治疗特发性中枢性性早熟女童的临床效果分析

目的探讨曲普瑞林治疗特发性中枢性性早熟女童的临床效果。方法选择我院2006年8月至2010年8月特发性中枢性性早熟女童共28例,本组患儿均给予曲普瑞林治疗,起初剂量为80～100μg/kg,肌肉注射,每隔30d注射一次,在治疗过程中根据患儿性腺抑制情况及身高增加情况调整剂量。在性腺抑制的前提下逐渐减量,维持生长速度>4cm/年。本组患儿连续治疗2年。观察本组患儿治疗前后骨龄指数、身高年龄对骨龄的追赶(HtSDSBA)、体质量指数、预测成年身高。结果本组患儿治疗后骨龄指数、身高年龄对骨龄的追赶(HtSDSBA)、体质量指数、预测成年身高分别与治疗前比较,差异有统计学意义(P<0.05)。结论曲普瑞林能够抑制特发性中枢性性早熟女童性腺轴及第二性征发育,有助于延缓骨龄成熟,疗效显著。     

曲普瑞林对特发性中枢性性早熟女童胰岛素敏感性影响

摘要：目的:观察促性腺激素释放激素类似物(GnRHa)曲普瑞林对特发性中枢性性早熟(ICPP)女童胰岛素敏感性的影响。方法:选取44例ICPP女童给予曲普瑞林治疗12个月。观察治疗前和治疗3个月、治疗6个月、治疗12个月时患儿的身高、体重、体重指数(BMI)、骨龄、空腹血糖、空腹胰岛素和血脂水平变化,采用稳态模型胰岛素抵抗指数(HOMA-IR)评估胰岛素敏感性。结果:治疗3个月时ICPP女童身高、体重、BMI及骨龄相比治疗前无明显变化(P>0.05);治疗6个月和治疗12个月时ICPP女童身高、体重、BMI较治疗前和治疗3个月时显著增加(P<0.05),而骨龄无明显变化(P>0.05);治疗12个月时ICPP女童的身高、体重、BMI、骨龄均较治疗6个月时明显增加(P<0.05)。治疗3个月时ICPP女童空腹血糖、空腹胰岛素、HOMA-IR与治疗前无明显变化(P>0.05);治疗6个月和治疗12个月时ICPP女童空腹血糖、空腹胰岛素、HOMA-IR均显著高于治疗前和治疗3个月(P<0.05),而治疗6个月和治疗12个月比较,差异无统计学意义(P>0.05)。患儿的血脂水平在整个观察期均无明显变化(P>0.05)。ICPP女童HOMA-IR增加与BMI增加无明显相关性。结论:曲普瑞林治疗可降低ICPP女童的胰岛素敏感性。     

应用注射用醋酸亮丙瑞林微球治疗的特发性中枢性性早熟女童血清胰岛素样生长因子1水平的变化及其与生长速度的关系

目的 探讨应用注射用醋酸亮丙瑞林微球治疗的特发性中枢性性早熟(ICPP)女童血清胰岛素样生长因子1(IGF-1)水平的变化及其与生长速度的关系。方法 回顾性分析2019年1月至2021年1月在北京积水潭医院儿科门诊诊断为ICPP的女童,从中筛选出仅应用注射用醋酸亮丙瑞林微球治疗且持续治疗1年以上的女童共42例。收集其治疗前、治疗6个月及1年后复查的病历资料,对比治疗前后身高、骨龄、骨龄预测终身高及IGF-1等指标变化,分析IGF-1水平变化与生长速度的关系。结果 治疗6个月及1年后骨龄预测终身高高于治疗前[(158±3)、(159±4)cm比(156±4)cm],差异均有统计学意义(均P<0.05);治疗1年后患儿身高增长速度明显慢于治疗前、IGF-1年龄范围的标准差明显低于治疗前[(2.8±1.3)cm/6个月比(3.6±1.1)cm/6个月、-0.16(-0.42,0.42)比0.86(0.24,1.84)],差异均有统计学意义(均P<0.05)。治疗1年后患儿身高增长速度与骨龄进展速度的延缓程度及雌二醇下降程度呈正相关(r=0.483,P=0.020;r=0.424,...     

不同疗程GnRHa治疗中枢性性早熟25例疗效比较

目的探讨促性腺激素释放激素类似物(GnRHa)治疗特发性中枢性性早熟(ICPP)的适宜疗程。方法厦门市第一医院儿科于2002年3月至2006年3月收治25例ICPP女童,随机分为两组,A组15例,年龄9.2±0.5岁,骨龄11.6±0.7岁,每4周肌肉注射曲普瑞林60～120μg/kg,疗程1年;B组10例,年龄8.7±0.9岁,骨龄11.2±0.5岁,每4周肌肉注射曲普瑞林60～120μg/kg,疗程2年。治疗过程中每月测量身高、体重、性征变化,每三个月监测骨龄(BA)、B超、预测身高(PAH)。结果经治疗骨龄增速减慢,A、B组骨龄变化与实际年龄变化的比值ΔBA/ΔCA分别由治疗前的1.23±0.07、1.29±0.12降低为0.62±0.25、0.53±0.06;两组患儿随疗程进展ΔBA/ΔCA比值均逐渐下降,治疗后BA的增长低于CA的增长。两组患儿治疗后预测成年身高在治疗6个月时即较治疗前有所改善,在治疗6个月及治疗1年时,两组差异无统计学意义;治疗后预测成年身高的增长值(ΔPAH),在治疗结束时B组比A组高(P<0.001)。结论GnRHa治疗中枢性性早熟疗程至少需6个月,治疗2年对终身高的改善更好。     

脑性瘫痪儿童56例生长发育状况分析

目的 分析脑性瘫痪儿童的生长发育状况,探讨青春期发育对脑瘫儿童成年身高的影响.方法 选择56例脑性瘫痪儿童作为研究对象,同期健康体检儿童34例作为对照,测量身高、体质量,检查性征发育情况,计算身高和体质量标准差、身高年龄、骨龄、预测成年身高、靶身高,并进行统计学分析.结果 脑性瘫痪组患儿身高标准差为(-1.29±1.39),体质量标准差为(-0.77 ±1.20),低于对照组的(0.40±0.95)和(0.38±1.01)(t=-6.270、-4.676,均P＜0.05).青春前期脑瘫组患儿生活年龄大于身高年龄和骨龄,差异均有统计学意义(t=6.381、7.939,均P＜0.05),身高年龄和骨龄差异无统计学意义(P＞0.05),预测成年身高和靶身高差异无统计学意义(P＞0.05).青春期脑瘫组患儿生活年龄和骨龄大于身高年龄,差异均有统计学意义(t=3.438、-3.759,均P＜0.05),生活年龄和骨龄差异无统计学意义(P＞0.05),预测成年身高低于靶身高,差异有统计学意义(t=-5.204,P＜0.05).结论 脑性瘫痪儿童生长发育落后,青春期发育的启动年龄和过程与正常儿童相似,青春期发育后骨龄增长加速,预测成年身高明显落后于靶身高.     

曲普瑞林治疗女童特发性中枢性性早熟的疗效观察

目的:观察促性腺激素释放激素类似物曲普瑞林治疗女童特发性中枢性性早熟(ICPP)的临床疗效。方法:选取某院2008—2012年确诊的68例ICPP女童,予曲普瑞林治疗1~2年,观察治疗前后乳房、子宫容积、卵巢容积、促黄体生成素峰值(P-LH)、促卵泡刺激素峰值(P-FSH)、血清雌二醇(E2)与随疗程进行的体质量指数(BMI)、骨龄(BA)、骨龄与生活年龄比值(BA/CA)、预测成年身高(PAH)、身高年龄对骨龄的追赶(HtSDSBA)、生长速率(GV)的动态变化及药物不良反应。同时选取52例未经治疗的ICPP患儿作为对照组,随访1~2年,测量各阶段乳房、子宫容积、卵巢容积、P-LH、P-FSH、E2以及BMI、BA等指标并进行比较。结果:治疗后患儿乳房、子宫、卵巢容积均有缩小,P-LH、P-FSH、E2均显著降低,骨龄成熟延迟,BA/CA值下降,身高年龄对骨龄的追赶、PAH治疗后较治疗前有改善,差异具有统计学意义(P<0.05);而未经治疗的对照组ICPP患儿乳房、子宫、卵巢容积有不同程度的增大,骨龄进展,BA/CA升高。结论:曲普瑞林治疗ICPP能有效抑制下丘脑-垂体-性腺轴及性征发育,延缓BA成熟,改善成年终身高。     

长效促性腺激素释放激素类似物治疗特发性中枢性性早熟的护理

特发性中枢性性早熟（JCPP）是一种内分泌疾病，是由各种原因引起的下丘腺-垂体-性腺轴功能发动提前，女孩8岁以前、男孩9岁以前呈现第二性征，骨龄超越年龄，骨骺提前融合而过早停止生长，致成年身高受损。治疗ICPP的目的是停止或减退第二性征发育，防止女童月经来潮，延缓骨龄成熟及最终改善成年身高，同时防止早熟和早初潮带来的心理问题。国内近年来广泛选用长效促性腺激素释放激素类似物（GnRHa）作为治疗ICPP的首选药物。我院性早熟专科门诊自2002年7月至2005年4月共诊断12例ICPP患儿，并应用GnRHa治疗，获得较满意的疗效，现报道如下。     

大补阴丸联合促性腺激素释放激素拮抗剂治疗女童中枢性性早熟的临床研究

目的观察大补阴丸联合促性腺激素释放激素拮抗剂(GnRHa)治疗女童中枢性性早熟的临床疗效。方法将83例中枢性性早熟女性患儿随机分为2组,对照组38例采用GnRHa(达菲林)药物治疗,治疗组45例在对照组治疗方法的基础上采用大补阴丸治疗,1年为1个疗程,对比治疗前、后2组患儿的子宫、卵巢大小,骨龄指数及性激素变化水平,同时记录患儿的身高增长速率及治疗期间不良反应发生情况。结果 2组治疗后子宫、卵巢大小,骨龄指数及性激素水平均显著下降,与治疗前比较差异有统计意义(P<0.05或P<0.01),且治疗组下降幅度优于对照组(P<0.01);对照组总有效率为71.05%,治疗组为88.89%,2组总有效率经统计学分析,差异有统计意义(P<0.05);对照组生长速率为(7.15±1.75)cm/年,治疗组为(4.96±1.34)cm/年,经统计学分析,差异有高度统计意义(P<0.01);2组患儿治疗期间未见不良反应发生。结论大补阴丸联合GnRHa治疗女童中枢性性早熟疗效显著,不良反应少,值得推广应用。     

Ergot drugs suppress plasma levels of prolactin (PRL) but not growth hormone (GH), luteinizing hormone (LH) or corticosterone (CORT) in parturient mice

Plasma levels of prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), and corticosterone (CORT) were measured in parturient Rockland-Swiss (R-S) albino mice following the daily administration for 10 days of 0.5 mg ergocornine (ERGO), 0.5 mg bromocriptine (BROMO), or sesame oil (OIL). The dams were provided with replete foster young on a daily basis so as to prevent the decline in suckling activity that normally occurs in undernourished pups of ergot-treated dams. Circulating PRL levels were significantly reduced by both ergot drugs but plasma levels of the other hormones measured were not altered. Thus, ergot drugs have relatively specific effects on PRL even in parturient animals receiving sustained high levels of suckling stimulation.     

The morphogenetic activity of juvenile hormone and analogues in Spodoptera littoralis Boisd (agrotidae-lepidoptera)

A biological assay system was developed for each of larva-pupa and pupa-adult moults in Spodoptera littoralis after treatment wih juvenile hormone (JH) and analogues. The larval characters retained after larva-pupaa ecdysis were associated with the route of administration. The sites of contact with the juvenilizing agent were the most frequently affected parts. Pupae were much more sensitive than last-instar larvae. A juveline hormone analouge (JHA) containing a methylene-dioxyphenyl group (MDP) was much more potent than the other compounds tested, including the synthetic juvenile hormone (SJH).     

GHRP-6对培养的垂体生长激素腺瘤和正常胚胎垂体细胞促GH分泌特征

目的　研究人工合成的生长激素释放剂GHRP 6对体外培养的人垂体生长激素腺瘤细胞GH分泌影响 ,并分析其可能的临床意义。方法　用原代细胞培养技术 ,观察了 6例垂体GH腺瘤细胞和 4例正常胚胎垂体细胞对GHRP 6、生长释放激素 (GH releasinghormone,GHRH)和生长抑素 (somatostatin ,SS)的体外分泌效应。 结果　GHRP 6对所有 6例GH腺瘤细胞GH分泌表现出明显的刺激效应 (P <0 0 1) ,但远不如正常垂体细胞敏感 ,但GH腺瘤细胞对持续的GHRP 6刺激反应时间延长。GHRH和SS仅对部分GH腺瘤细胞有作用 ,且SS不能完全阻断GHRP 6对于GH分泌的刺激效应。结论　GH腺瘤细胞对于体外GHRP 6持续刺激的异常反应 ,表明垂体GH腺瘤中可能存在GH释放剂受体 (GHS R)所固有的负反馈机制———“脱敏”机制的减弱 ,且与肿瘤发病机制有关     

Growth Hormone (GH) Secretory Dynamics in Animals Administered Estradiol Utilizing a Chemical Delivery System

We have utilized a redox chemical delivery system (CDS) for the brain targeting of estradiol (E₂) to ascertain its effects on GH secretory patterns in adult intact male rats. The E₂-CDS (1.0 mg/kg) dissolved in 20% hydroxypropyl-cyclodextrin (HPCD), E₂ (1.0 mg/kg) alone in 20% HPCD, or 20% HPCD was administered intravenously. GH secretory profiles, plasma steroid levels, and anterior pituitary levels of hormones were determined 1 week following steroid injection. Whereas E₂ in HPCD and HPCD treatment did not alter masculine GH secretory patterns, animals administered the E₂-CDS displayed disrupted GH patterns with attenuated individual pulse amplitudes and significantly elevated GH baseline levels. Moderate pituitary hyperplasia was evident only in the E₂-CDS group of animals. Plasma testosterone (T) concentrations were reduced in only the E₂-CDS group. T replacement reduced E₂-CDS-associated pituitary hyperplasia and preserved the masculine GH secretory profiles, with only a slight reduction in individual GH peak amplitudes being observed. T replacement did not prevent the increase in pituitary and plasma levels of PRL associated with E₂-CDS treatment but did block both the increase in pituitary GH content and the hyperplasia associated with prolonged E₂ exposure. E₂ given alone induced a significant increase in both GH and PRL in the pituitary without establishment of pituitary hyperplasia or elevated plasma PRL levels. These data indicate that E₂-CDS is an effective mode of steroid administration. Changes in GH secretory dynamics, pituitary levels of GH, and degree of hyperplasia are dependent upon the chemical design of the delivery system for E₂. Concomitant T therapy can prevent some of the changes in GH secretion associated with high-dose E₂ exposure.     

Restoration of Spermatogenesis in Dibromochloropropane (DBCP)-Treated Rats by Hormone Suppression

The exposure of men to the nematocide dibromochloropropane (DBCP)has caused prolonged oligo- and azoospermia, which occasionallyreverses spontaneously. We recently demonstrated that in testesof rats treated with a dose of DBCP sufficient to reduce thepercentage of tubules producing differentiating germ cells (tubuledifferentiation index, TDI) to 20%, the tubules lacking differentiatingcells contained type A spermatogonia. To determine whether thesetype A spermatogonia could be stimulated to differentiate, ashad been demonstrated previously in other models of toxicant-inducedsterility, we suppressed intratesticular testosterone and serumfollicle stimulating hormone (FSH) levels with the GnRH agonistLupron (leuprolide). When the GnRH agonist was given for 10weeks starting immediately after DBCP exposure, the TDI wasmaintained at 94%. Even when GnRH-agonist treatment was stoppedat week 10, the TDI remained between 65 and 80% 10 weeks later.Late spermatid counts averaged 10 x 10⁶ per testis for the GnRH-agonist–treatedrats at week 20 compared with 1.7 x 10⁶ per testis in rats treatedwith only DBCP. To determine whether spermatogonial differentiationcould be stimulated after the TDI had declined to below 30%,we initiated GnRH-agonist treatment 6 weeks after DBCP exposure.The GnRH treatment increased the TDI to 53% at week 16. Theseresults indicate that, if the same principles apply to humans,suppression of testosterone may be applied to restore spermatogenesisin men rendered azoospermic by DBCP or other reproductive toxicants.     

促黄体释放素类似物和促甲状腺激素释放激素对青少年型日本血吸虫病性侏儒症的促生长发育作用

为了观察在杀虫治疗后使用国产促黄体释放素类似物D一丙~6-LRH和促甲状腺激素释放激素对青少年型日本血吸虫病性侏儒症患者促生长发育作用的远期效果,作者对19例已作治疗的患者进行了连续3-4yr的随访观察。结果发现身高、体重和性发育情况均有明显改善,并以2药合用为优。不论近期或远期效果均甚满意,值得临床进一步研究。     

A comparison between amantadine and bromocriptine using the stereotyped behaviour response test (SBR) in the rat.

Amantadine (100 mg/kg), apomorphine (2.5-10 mg/kg) and bromocriptine (10-50 mg/kg) all produced stereotyped behaviour in the rat. Apomorphine was rapid in onset and of short duration, amantadine was slower to reach a maximum and bromocriptine had a delayed onset of 50 min and a prolonged action. Amantadine and bromocriptine were antagonised by pimozide (1 mg/kg for 30 min) suggesting an action on dopamine receptors, and by D,L-alpha-methyl-p-tyrosine (150 mg/kg for 3 h) suggesting an indirect action. Amantadine, though not bromocriptine, antagonised apomorphine and amantadine also reversed the SBR due to bromocriptine. Pretreatment of rats with p-chlorophenylalanine (100 mg/kg twice daily for 2 days) had no effect on bromocriptine. The significance of these results is discussed with reference to the proposed mechanism of action of bromocriptine and to the use of multiple drug therapy in Parkinsonism.     

The Stability of Recombinant Human Growth Hormone in Poly(lactic-co-glycolic acid) (PLGA) Microspheres

Purpose. The development of a sustained release formulation for recombinant human growth hormone (rhGH) as well as other proteins requires that the protein be stable at physiological conditions during its in vivo lifetime. Poly(lactic-co-glycolic acid) (PLGA) microspheres may provide an excellent sustained release formulation for proteins, if protein stability can be maintained. Methods. rhGH was encapsulated in PLGA microspheres using a double emulsion process. Protein released from the microspheres was assessed by several chromatrographic assays, circular dichroism, and a cell-based bioassay. The rates of aggregation, oxidation, diketopiperazine formation, and deamidation were then determined for rhGH released from PLGA microspheres and rhGH in solution (control) during incubation in isotonic buffer, pH 7.4 and 37°C. Results. rhGH PLGA formulations were produced with a low initial burst (<20%) and a continuous release of rhGH for 30 days. rhGH was released initially from PLGA microspheres in its native form as measured by several assays. In isotonic buffer, pH 7.4 and 37°C, the rates of rhGH oxidation, diketopiperazine formation, and deamidation in the PLGA microspheres were equivalent to the rhGH in solution, but aggregation (dimer formation) occured at a slightly faster rate for protein released from the PLGA microspheres. This difference in aggregation rate was likely due to the high protein concentration used in the encapsulation process. The rhGH released was biologically active throughout the incubation at these conditions which are equivalent to physiological ionic strength and pH. Conclusions. rhGH was successfully encapsulated and released in its fully bioactive form from PLGA microspheres over 30 days. The chemical degradation rates of rhGH were not affected by the PLGA microspheres, indicating that the internal environment of the microspheres was similar to the bulk solution. After administration, the microspheres should become fully hydrated in the subcutaneous space and should experience similar isotonic conditions and pH. Therefore, if a protein formulation provides stability in isotonic buffer, pH 7.4 and 37°C, it should allow for a safe and efficacious sustained release dosage form in PLGA microspheres.