重组人生长激素2种制剂人体生物等效性研究

目的:评价重组人生长激素(rhGH)注射液(2种规格:T1和T2)与注射用rhGH冻干粉针剂(参比制剂,R)的人体生物等效性。方法:运用随机、单盲、三阶段交叉方法分别对24名健康男性志愿者单次皮下注射0.2IU·kg-1的R,T1和T2。测定不同时间点生长激素血药浓度,并进行相关药动学参数分析。结果:T1,T2的AUC0～24的90%置信区间分别落在R的103.4%～116.5%和105.7%～119.6%范围内,T1的AUC0～24的90%置信区间落在T2的91.9%～103.7%范围内;T1和T2的cmax的90%置信区间分别落在R的91.9%～114.0%和103.7%～127.2%范围内,T1的cmax的90%置信区间亦落在T2的81.6%～97.4%的范围内。tmax在R及T1,T2间无统计学差异(P>0.05)。结论:T1,T2与R具有生物等效性。     

重组人生长激素治疗肝硬化低清蛋白血症

目的:观察重组人生长激素(rhGH)治疗肝硬化引起的低清(白)蛋白血症的临床疗效。方法:选择血清清蛋白低于30g·L-1的肝硬化病人46例,男性39例,女性7例,分为治疗组、对照组各23例。治疗组在常规保肝及对症治疗基础上,给予rhGH,4IU,皮下注射,每日1次,连续14d;对照组仅给予常规保肝及对症治疗,14d为一个疗程。检测2组病人治疗前及治疗结束d1和4wk后血清清蛋白及其他肝功能指标变化,并进行临床观察。结果:治疗组治疗前血清清蛋白(25±s3)g·L-1,治疗结束d1血清清蛋白(31±3)g·L-1(P<0.01),4wk后血清清蛋白(33±3)g·L-1(P<0.01);对照组治疗前血清清蛋白(25±3)g·L-1,治疗结束d1血清清蛋白(25±3)g·L-1,4wk后血清清蛋白(24.4±2.6)g·L-1(P>0.05),2组治疗结束d1及4wk后血清清蛋白相比,差异有非常显著意义(P<0.01)。治疗结束d1及4wk内治疗组比对照组病人精神状态、食欲、尿量、腹腔积液、肝功能等均明显改善且持续稳定,有显著差异(P<0.05)。无明显不良反应。结论:rhGH可以增加肝硬化病人的血清清蛋白的水平,改善营养状况,无明显不良反应。     

重组人生长激素在体外对人肝癌细胞系SMMC7721的作用

[目的]研究重组人生长激素（recombinant human growth hormone，rhGH）在体外对人肝癌细胞系SMMC7721生长的影响[方法]实验分为对照组、rhGH组、rhGH＋阿霉素fAdriamycin，ADM）组及ADM组；通过体外细胞培养、四甲基俏氯唑蓝（MTT）比色技术及流式细胞术等手段．测定不同浓度的rhGH及其与ADM合用时对人肝癌细胞系SMMC7721的生长曲线、细胞抑制率、细胞周期及增殖指数（PI）的影响.[结果]与对照组相比，不同浓度的rhGH在体外对人肝癌细胞系SMMC7721的分裂增殖无明显影响（P〉0．05），生长曲线不随rhGH浓度的增加而升高；rhGH＋ADM组与ADM组比较细胞抑制率和生存率差异均无湿著性（P〉0．05），生长曲线无明显差异；与对照组及rhGH组相比较，单用ADM或rhGH＋ADM对该细胞的抑制率增加、PI明显减少（P〈0．01），而在单用ADM和rhGH＋ADM组间差异均无统计学意义（P〉0．05）：[结论]rhGH在体外对人肝癌细胞系SMMC7721的分裂增殖无明显促进作用．对ADM的抗癌作用无明湿影响。     

A Controlled Trial of Methionyl Growth Hormone Therapy in Prepubertal Children with Short Stature, Subnormal Growth Rate and Normal Growth Hormone Response to Secretagogues

ABSTRACT. Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group ( n = 20) undergoing treatment with methionyl GH (somatrem), 2IU per m² body surface s.c. daily, or a control group ( n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity ( r = 0.8) and the short-term height velocity increment ( r = 0.7–0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

Preliminary Results of Authentic Recombinant Somatropin Treatment in Human Growth Hormone Deficient Children. French Collaborative Study

A total of 50 children with hGH deficiency have been enrolled in a multicentre open trial of recombinant somatropin in France. Recombinant somatropin, 0.2 IU/kg s.c, was administered 3 times/week (0.6 IU/kg/week). Results are available after 3 months'treatment for 24 of the patients (11 prepubertal, 13 pubertal). The mean growth rate increased from 3.8 ± 1.5 cm/year to 9.9 ± 3.6 cm/year. Only one child developed anti-hGH antibodies with a very low binding capacity of 0.02 mg/litre; adverse events were uncommon and probably unrelated to treatment.     

原发性肝癌组织生长激素受体的表达

为探讨重组人生长激素 (rhGH)在肝癌患者中的适用问题 ,采用放射配体法对 32例原发性肝癌 (HCC)组织进行了生长激素受体 (GHR)的检测。结果在 2 8例HCC组织检测到GHR ,GHR受体结合容量 (RT)为 (18 430 0± 4 16 33)fmol/mg蛋白 ,平衡解离常数 (Kd)为 (0 6 432± 0 196 1)nmol/L ,与正常肝组织相比 ,其RT降低 (P <0 0 5 ) ,Kd无显著性改变 (P >0 0 5 ) ;HCC组织GHR的结合容量与肿瘤大小呈负相关 ,而与肿瘤分化程度、患者是否合并肝硬化无明显相关 ;有 4例肝癌组织未检测到GHR存在。研究提示 :大多数原发性肝癌组织仍表达低水平GHR ,在其功能未明的情况下 ,rhGH在肝癌患者中的使用应慎重。     

肝硬化大鼠肝部分切除术后肝再生的干预研究

目的　以肝硬化大鼠为动物模型 ,研究药物对肝硬化大鼠肝部分切除术后肝再生的影响。方法　取健康的Wistar雄性大鼠 6 4只 ,以 6 0 ?l4油溶液 0 .3ml/ 10 0 g皮下注射 ,同时饮用 5 %酒精溶液 ,4 5d后制成肝硬化动物模型。模型大鼠随机分为 4组 ,16只 /组。全麻下均行左、中叶肝切除术。术后各组按以下方案处理 :A组 (对照组 )注射生理盐水 1mg/ (kg·d) ,B组为泮托拉唑组 ,注射 0 .2mg/ (kg·d) ,C组为重组人生长激素组 ,注射 0 .5U/ (kg·d) ,D组为两药合用组 ,同时给予泮托拉唑注射 0 .2mg/ (kg·d) ,重组人生长激素注射 0 .5U/ (kg·d) ) ,连续给药 1周。抽取静脉血样 ,取肝脏组织 ,检测肝功能、有丝分裂指数 (MI)、增殖细胞核抗原 (PCNA)、细胞核DNA含量。结果　泮托拉唑组、重组人生长激素组、两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于对照组 (P <0 .0 5 ) ,两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于泮托拉唑组、重组人生长激素组 (P <0 .0 5 ) ,但各组间肝功能变化无明显差异。结论　泮托拉唑组及重组人生长激素均对肝硬化大鼠肝部分切除术后肝细胞再生有促进作用 ,两药联合应用肝细胞再生更明显 ,其详细机制须待进一步研究。     

国产重组人生长激素治疗儿童生长激素缺乏症临床疗效观察

正确评价国产重组人生长激素对促进生长激素缺乏症儿童身高增长作用的疗效和安全性，观察相关血清生化指标的变化，方法：造反２ＣＨＤ患儿９例，给予国产ｒ－ｈＧＨ０．１ｉｕ／ｋｇ．ｄ；疗程６个月。结论国产ｒ－ｈＧＨ治疗ＧＨＤ近期疗效肯定，而且安全可靠。     

重组人生长激素联合5-氟尿嘧啶对表达或不表达生长激素受体人肝癌细胞的体外干预

目的研究重组人生长激素（rhGH）在体外对表达或不表达生长激素受体（GHR）的人肝癌细胞系的影响。方法采用免疫组织化学方法检测人肝癌细胞系的GHR表达。每种肿瘤细胞系分4组进行处理：未处理组、5-氟尿嘧啶（5-Fu）处理组、rhGH处理组及5-Fu＋rhGH联合处理组。采用四甲基偶氮唑蓝（MTT）比色法及流式细胞术分析不同浓度rhGH及其与5-Fu合用对人肝癌细胞系的生长抑制、凋亡、细胞周期及增殖指数（PJ）等的影响。结果Bel-7402细胞表达GHR；与未处理组相比，各浓度rhGH组的生长率、G2／M期比例和PI显著升高，细胞凋亡率显著降低（P均〈0．05）；与5-Fu处理组相比，各浓度rhGH＋5-Fu组的G2／M期比例和PI显著升高，抑制率和细胞凋亡率显著降低（P均〈0．05）。SMMC7721不表达GHR；不同浓度rhGH对该细胞系的分裂增殖无明显影响（P均〉0．05）；rhGH＋5-Fu联合处理组与5-Fu处理组问的细胞抑制率、凋亡率及Pl差异也无显著性（P均〉0．05）。结论rhGH在体外能促进GHR^＋的肝癌细胞增殖，减弱5-Fu对GHR^＋细胞的抗癌作用，但对GHR^-的肝癌细胞无明显影响，也不能明显干扰5-Fu对GHR^-细胞的抗癌功能。