肝硬化患者生长激素抵抗的可能机制探讨

目的探讨IGF-Ⅰ及其结合蛋白-3(IGFBP-3)与肝硬化患者生长激素抵抗的关系,研究肝硬化患者生长激素抵抗的另一可能机制.方法肝硬化患者65例,按Child-pugh分级法将其分为A(17例),B(20例)和C(28例)三组,对照组30例,应用放射免疫法检测空腹IGF-Ⅰ和IGFBP-3及GH水平.结果肝硬化患者血清IGF-Ⅰ和IGFBP-3水平下降(100.49±38.11 ng/mL对352.55±153.61 ng/mL,P＜0.001;45.02±16.21 nmol/L对114.50±27.09 nmol/L,P＜0.001),而GH水平明显升高(6.02±4.03对0.28±0.40,P＜0.001),IGF-1、IGFBP-3与GH呈负相关(r=-0.728,r=-0.569,P＜0.01).结论肝硬化患者存在生长激素抵抗,IGF-Ⅰ、IGFBP-3可能与肝硬化患者的生长激素抵抗有关.     

重型肝炎患者血清胰岛素样生长因子-1含量及其临床意义

目的:研究重型肝炎患者血清胰岛素样生长因子(IGF-1)含量的动态变化及其对评估重型肝炎预后的意义.方法:采用ELISA定量检测47例重型肝炎患者及18例健康体检者血清IGF-1含量,同时检测有关肝功能指标.结果:死亡组治疗前IGF-1含量显著低于正常对照[(186.37±71.46)ng/ml vs (247.06±48.81)ng/ml,P＜0.01],其死亡前含量显著低于入院时含量[(131.70±43.79)ng/ml vs (186.37±71.46)ng/ml,P＜0.01].存活组治疗前IGF-1含量和正常对照组差异无显著性意义[(209.44±71.96)ng/ml vs (247.06±48.81)ng/ml,P＞0.05],其治疗后含量显著高于死亡组死亡前含量[(198.55±56.68)ng/ml vs (131.70±43.79)ng/ml,P＜0.01].IGF-1含量和部分肝功能指标(PTA、CHO、CHE)相关(P＜0.05).结论:IGF-1可以反映肝细胞增生情况,动态检测能较好预测重型肝炎发展趋势,对评估重型肝炎预后有一定价值.     

肝硬化患者胰岛素抵抗的另一可能机制初近探

肝硬化患行普遍存在高胰岛素血症(1ns)和胰岛素抵抗,胰岛素样生长因子I(1GF-I)的合成受Ins的影响.为探ICF-Ⅰ及其结合蛋门-3(IGFBP-3)与肝硬化患者胰岛素抵抗的关系,本文应用放射免疫法检测了65例肝硬化患者血清IGF-Ⅰ和IGFBP-3及Ins水平.结果表明肝硬化患者血清IGF-Ⅰ和IGFBP-3水平下降(100.49±38.11ng/ml对352.55±153.61ng/ml,P＜0.001;45.02±16.21nm01/L对114.50±27.09nm01/L,P＜0.001),而Ins水平明显升高(30.38±13.21对5.69±3.47,P＜0.001),IGF-Ⅰ、IGFBP-3与His呈负相关(P＜0.01).结论肝硬化患者存在胰岛素抵抗,IGF-Ⅰ、IGFBP-3可能与肝硬化患者的胰岛素抵抗有关.     

肝硬化患者血清IGF—Ⅱ和HA测定及临床意义

目的探讨胰岛素样生长因子Ⅱ(IGF-Ⅱ)在肝硬化病人血清中的变化及临床意义.同时探讨IGF-Ⅱ和透明质酸(HA)之间的关系.方法肝硬化患者80例,对照组77例,应用放射免疫法检测空腹IGF-Ⅱ和HA.结果肝硬化患者血清中的IGF-Ⅱ水平明显低于对照组(162.05±103.84ng/ml vs 575.31±194.87 ng/ml,P＜0.001),肝硬化患者血清中HA水平明显高于对照组(415.18±288.28 ng/ml vs 61.75±28.68 ng/ml,P＜0.05),且患者IGF-Ⅱ水平与预后呈正相关.结论 IGF-Ⅱ水平可反应肝功能的剩余能力,也可作为动态观察肝功能变化的指标之一,有助于疗效判断和预后估计.     

051 1型糖尿病患者停用胰岛素时游离IGF-1及瘦素水平的变化

[英]/Attia N…//J Clin Endocrinol Metab.-1999,84.-2324～2328 有报道胰岛素样生长因子(IGF)-1缺乏与糖尿病的血糖控制不良、代谢紊乱有关。另有试验发现空腹时瘦素(leptin)水平下降,而进食后瘦素水平回升,因此推测瘦素的变化与胰岛素有关。为此本试验观测了1型糖尿病患者胰岛素水平短期内变化时IGF-1及其结合蛋白(IGFBP)和瘦素水平的变化。 对象和方法17例持续皮下注射胰岛素的1型糖尿病患者为受试者,平均年龄(31±10)岁,糖化血红蛋白(HbAlc)平均水平7.6％,平均体重指数(BMI)女性为(24±1)kg／M2(16.7～28.3 kg/m2),男性为29.1 kg/(235 kg／m2)。受试者胰岛内分泌功能均已丧失,无肾功损害、糖尿病大血管并发症及其他慢性病者。 试验分2阶段。第1阶段受试者停止注射胰岛素8 h,期间有血糖超过19.425 mmol／L或尿中出现酮体++以上者恢复胰岛素的治疗。第2阶段于停用胰岛素8 h后恢复治疗2 h。每30min采血测受试者血糖、胰岛素、IGF-1、胰升糖素、游离IGFBP-1、IGFBP-3、生长激素(GH)、肾上腺素、去甲肾上腺素的水平。并于试验前、停用胰岛素6 h、8 h及恢复治疗1 h、2 h采血测瘦素及游离脂肪酸水平。 结果 停用胰岛素后,血胰岛素水平由(60.0±12.0)pmol／L降至(10.8±4.2)pmol／L,血糖由(5.6±0.4)mmol／L升至(14.8±1.2)mmol／L(P＜0.01),而IGFBP-1至少增加了6倍[由(32±8)μg/L升至(205±17)μg/L,P＜0.001],IGFBP-3亦显著增加[由(2 631±118)μg/L升至(3 053±101)μg/L,P＜0.001],总IGF-1水平中度下降[由(226±33)μg/L降至(182±26)μg／L,P＜0.001],而游离IGF-1水平则明显降低,17例受试者中有15例IGF-1水平低于可测试的最低值(P＜0.001)。血清瘦素水平显著下降,女性由(20±3)μg/L降至(11±2)μg/L(P＜0.0001),男性由(10±2)μg/L降至(7±2)μg/L(P＜0.02)。恢复胰岛素治疗的2 h内,血中IGFBP-1、IGFBP-3的水平有所回升,游离IGF-1水平升至(0.54±0.22)μg/L(与停用胰岛素时游离IGF-1水平相比P＜0.01),而瘦素水平在恢复治疗的2 h内继续下降。GH、胰升糖素和IGFBP-2的水平在试验中无明显变化。 结论 研究结果显示1型糖尿病患者停用胰岛素时,受其诱导的IGFBP急速改变是IGF-1生物利用度的重要调节剂,另外胰岛素具有调节瘦素水平的作用。 (矫 杰摘 蒋 玲校)     

原发性高血压赖诺普利治疗前后血清胰岛素样生长因子-Ⅰ的变化

目的观察原发性高血压(EH)患者服用赖诺普利治疗前后血清胰岛素样生长因子-Ⅰ(IGF-Ⅰ)的变化,探讨IGF-Ⅰ在EH的发生发展过程中所起的可能作用.方法47例EH患者均行超声心动图检查,用放免法测定赖诺普利治疗前、治疗后半年及23例正常对照者血清IGF-Ⅰ水平.结果EH患者血清IGF-Ⅰ水平明显高于对照组分别为(22.23±10.06)ng/ml对(15.91±7.59)ng/ml,P＜0.01.Ⅰ～Ⅲ级间比较也有显著性差异(F=3.53,P＜0.05),Ⅲ级(28.61±13.10)ng/ml高于Ⅱ级(22.64±9.94)ng/ml,Ⅱ级高于Ⅰ级(18.09±6.11)ng/ml.EH伴左心室肥厚(LVH)者高于无LVH者(25.95±11.20)ng/ml对(18.68±7.43)ng/ml,P＜0.05.IGF-Ⅰ与左心室重量指数中度相关(r=0.54).赖诺普利治疗6个月后,血清IGF-Ⅰ水平由(22.23±10.06)ng/ml降至(16.82±7.93)ng/ml,P＜0.05.结论EH LVH患者IGF-Ⅰ水平升高,赖诺普利治疗后IGF-Ⅰ水平下降,IGF-Ⅰ可能参与EH LVH的形成.     

甲胎蛋白在重型肝炎中改变的分析

目的了解重型肝炎患者甲种胎儿球蛋白(AFP)的变化.方法38例重型肝炎患者,根据临床转归分为存活组和死亡组.入院后动态观察AFP的改变.用放免法检测血清AFP.结果38例重型肝炎患者的AFP(205.64±289.78)ng/ml,显著高于正常值(8.1ng/ml),P＜0.001.存活组22例患者的AFP(225.03±65.16)ng/ml,显著高于正常值,P=0.003.但是,两组间的AFP差异无显著性意义(P=0.63).38例重型肝炎中,6例患者的AFP在700～900 ng/ml之间,10例在100～500 ng/ml之间,其余均高于正常值的2～10倍(尤以存活组较为明显),仅4例在正常值范围之内.结论重型肝炎有强烈的肝细胞再生现象,肝细胞再生能力对患者的预后有一定影响.     

格列吡嗪对2型糖尿病病人血清胰岛素样生长因子及其结合蛋白的影响

目的探讨格列吡嗪治疗对2型糖尿病病人血清胰岛素样生长因子（IGF）及其结合蛋白（IGFBP）的影响。方法采用病例对照及治疗前后自身对照研究,了解糖尿病病人空腹血清IGF-1、IGF-2和IGFBP-1、IGFBP-3水平及格列吡嗪治疗2周后的改变情况。其中糖尿病组40例,正常对照组90例,两组年龄无显著性差异,P＞0.05。结果与正常对照组比,糖尿病组治疗前IGF-1水平降低（234.41±141.78vs181.76±104.48ng/mlP＜0.05）,IGFBP-1水平升高(47.65±31.78vs68.82±43.18ng/ml,P＜0.01),IGF-2和IGFBP-3改变不明显。格列吡嗪治疗后IGF-I升高(181.8±104.5vs209.0±88.2ng/ml,P＜0.05);IGFBP-1则明显下降(68.82±43.18vs43.72±34.35ng/ml,p=0.001);IGF-II,IGFBP-3无明显变化。结论格列吡嗪治疗可改善2型糖尿病所导致的血清IGF-I和IGFBP-1水平改变。     

糖尿病患者(97例)血清生长激素与血糖及胰岛素之间相互关系及动态变化的临床意义

本文对97例糖尿病患者同时测定空腹血糖、血清生长激素(GH)和胰岛素等三项共148例次。总结分析发现:(1)糖尿病患者GH水平(7.81±4.13ng/ml)比正常人(1.10±0.65ng/ml,n=31)显著增高(P<0.01)。(2)在不同血糖水平的轻、中、重型患者,其GH水平(分别为5.33±2.52、8.87±3.78、12.53±2.33ng/ml)也有显著差异(P均<0.01)。     

慢性病毒性肝炎患者血清内毒素结合蛋白的临床意义

目的探讨血清内毒素结合蛋白(LBP)与肝脏炎症程度之间的关系。方法采用酶联免疫吸附法(ELISA)检测99例慢性病毒性肝炎患者血清中LBP水平,其中33例慢性重型肝炎患者入院后2~4周复查LBP。结果肝炎组LBP值(79.62±45.52)ng/ml高于正常对照组(50.22±31.44)ng/ml(P=0.001)。慢性重型肝炎组血清LBP值明显高于慢性肝炎中、重度及正常人(P<0.05)。慢性重型肝炎治疗后好转组LBP值明显低于病死组及治疗前LBP值(P<0.01),抗菌治疗组LBP值明显低于未抗菌治疗组及治疗前(P<0.01)。抗菌治疗组好转率64.3%(11/17)明显高于未抗菌治疗组25.0%(4/16)。LBP与血清白蛋白、胆碱酯酶、血红蛋白呈负相关,与血清总胆红素、Ⅲ型前胶原、凝血酶原时间呈正相关。结论慢性肝炎患者血清LBP增高与肝脏损害程度密切相关,治疗后LBP值下降者预后较好。     

Pubertal growth and growth hormone secretion

A dramatic increase in linear growth velocity, often referred to as the pubertal growth spurt, is a central feature of pubertal development. Despite the existence of numerous investigative attempts, a precise understanding of the hormonal events subserving this process has proved elusive. Nevertheless, evidence has gradually accumulated that indicates that sex steroid-induced modulation of growth hormone secretion is a central and critical feature of the pubertal growth spurt. As a result, disorders of either growth hormone or sex steroid hormone production may result in clinical growth disorders during puberty.     

The growth hormone receptor in growth.

The growth hormone receptor (GHR) is a major effector of Human growth. Functional variants of the GHR include very rare loss-of-function mutations (pathology) and very common polymorphisms (physiology). Recent experimental data have clarified the mechanisms through which mutations of the GHR or Stat5 lead to growth hormone insensitivity and major monogenic growth defects. Recent pharmacogenetic studies support that the response to growth-promoting administration of growth hormone is influenced by exon 3 polymorphism of the GHR.     

Normal growth and techniques of growth assessment

The shape of the human growth curve is described and illustrated. Growth studies may be longitudinal, cross-sectional, mixed longitudinal or linked-longitudinal; each has advantages and disadvantages, and each requires appropriate statistical methods for handling the data. Standards for height and height velocity for use in a clinical setting wherein follow-up over several years is presumed are described and illustrated. Such standards have to take into account tempo of growth at ages over nine years. Cross-sectionally derived standards do not do this and are not suitable for clinical use. The techniques of measurement of height, sitting height and skinfolds are described and illustrated. Growth and development during puberty is described; there are changes in body composition as well as in body size and shape. Standards for pubertal stages of breasts, pubic hair and genitalia are given and emphasis is laid on the great variation in both the timing and the duration of these pubertal changes. Measurement of developmental age is discussed. The Greulich-Pyle and Tanner-Whitehouse methods for skeletal age are described. These methods can be used for predicting adult height which is useful both in diagnosis and in following the effects of treatment. In diagnosis the predicted adult height is compared to the range of expected heights in the children of the particular pair of parents concerned (the so-called 'target' range of heights) to see if smallness is simply due to delay. Change in Tanner-Whitehouse predicted height occurs on successful treatment of, for example, growth hormone deficient short stature, and is thus a guide to the success of treatment. Standards are also given for height of children from age two to nine inclusive, with allowance for height of their parents.     

Mammalian epidermal growth factor promotes plant growth

Application of mouse submaxillary gland epidermal growth factor to young sorghum seedlings at low concentrations (≈0.4-4 μM) increased shoot growth significantly over 3- and 6-day periods. The effects were dose dependent.     

Predicting the growth response to growth hormone in patients with intrauterine growth retardation

OBJECTIVE Human GH treatment of short children who had intrauterine growth retardation (IUGR) results in a highly variable growth response. The object of this study was to test the hypothesis that differences in responsiveness to exogenously administered GH might reflect differences in endogenous GH secretion or sensitivity. DESIGN Prospective study evaluating the growth response to GH therapy in short individuals with prior IUGR. PATIENTS Ten short, prepubertal children with prior IUGR were studied. Mean age was 6 years (3.39–8.61). Mean bone age was 4.6 years (2.3–8.3). Mean body mass index was 13.2 kg/m² (9.9–14.0; normal 13.5–19.0). MEASUREMENTS Overnight spontaneous GH release was measured using a constant withdrawal pump and stimulated GH release was measured following clonidine (0.15 mg/m²) administration. IGF-I concentrations were measured at baseline and 12, 24, 36 and 48 hours after sequential doses of GH (0.05 and 0.2 mg/kg/dose) given 48 hour apart. Patients were treated with GH (0.125 mg/kg three times a week) and growth response was assessed. In the second and third year, attempts were made to improve the growth rate by nutritional supplementation and increasing the dose of GH to 0.25 mg/kg three times a week. RESULTS All patients had normal integrated nocturnal GH secretion (>3 μg/l, 6mU/l) and normal peak GH secretion in response to clonidine (>7 μg/l). In the first year of the trial, mean growth velocity (GV) increased from 5.39 cm/year ± 0.29 to 7.32 cm/year ± 0.39 (P = 0.004). Changes in GV correlated inversely with integrated GH (r = ? 0.69; P = 0038), baseline IGF-I concentration (r = ? 0.88; P = 0.002) and baseline GV-SDS (r = ? 0.68; P = 0.043). There was no correlation between change in GV and GH binding protein, baseline height SDS or age. The effect of GH waned in the second year, but tended to remain greater than the pretreatment growth rate (6.54 ± 0.49 vs 5.53 cm/year ± 0.29; P = 0.09). No significant advancement of bone age over chronological age was observed over the first 2 years. Increasing nutritional intake by 17% did not result in significant weight gain nor increase in height velocity. Doubling the dose of GH in the second or third year did not result in a significant increase in GV. CONCLUSION The variable response to GH therapy in short children with a history of intrauterine growth retardation may partly reflect relative sufficiency or insufficiency of GH. Baseline IGF-I levels and baseline growth velocity appear to be useful and practical predictors of response to GH.     

Interactions between growth hormone, insulin-like growth factor I, and basic fibroblast growth factor in melanocyte growth.

Melanocytes, highly differentiated neural crest-derived cells, are located in the basal layer of the epidermis, where they play a role in protecting against UV damage in the skin. Previous studies suggest that both growth hormone (GH) and the insulin-like growth factor I (GH/IGF-I) system may be important for melanocyte growth and function. We have therefore characterized the role of the GH/IGF system in melanocyte growth in vitro and its interaction with the local growth factor basic fibroblast growth factor (bFGF). Analysis of the effects of GH, IGF-I, and bFGF and combinations of these growth factors on melanocyte growth in vitro revealed that 1) GH stimulates the growth of melanocytes when combined with IGF-I, des(1-3)IGF-I [an analog of IGF-I that has a reduced binding affinity for IGF-binding proteins (IGFBPs)], or bFGF, either separately or in combination; 2) in contrast to the lack of effect of GH or bFGF alone, both IGF-I and des(1-3)IGF-I enhance melanocyte growth in a dose-dependent manner; and 3) IGF-I is more efficacious in eliciting a growth response at low concentrations compared to des(1-3)IGF-I. Using Western ligand blotting, affinity cross-linking, immunoprecipitation, RIA, and Northern analysis, we show that cultured human melanocytes synthesize and secrete minimal amounts of IGFBP. IGFBP-4 is the major IGFBP produced by these cells when cultured in complete growth medium or in the presence of either IGF-I or des(1-3)IGF-I alone. In conclusion, these studies provide support for a role for both GH and IGF-I in the growth of human melanocytes in vitro, involving synergy with bFGF. Low levels of melanocyte-derived IGFBP-4 may play a role in enhancing the modulation of IGF action.     

Growth cartilage expression of growth hormone/insulin-like growth factor I axis in spontaneous and growth hormone induced catch-up growth

IntroductionCatch-up growth following the cessation of a growth inhibiting cause occurs in humans and animals. Although its underlying regulatory mechanisms are not well understood, current hypothesis confer an increasing importance to local factors intrinsic to the long bones' growth plate (GP).AimThe present study was designed to analyze the growth-hormone (GH)-insulin-like growth factor I (IGF-I) axis in the epiphyseal cartilage of young rats exhibiting catch-up growth as well as to evaluate the effect of GH treatment on this process.Material and methodsFemale Sprague–Dawley rats were randomly grouped: controls (group C), 50% diet restriction for 3 days + refeeding (group CR); 50% diet restriction for 3 days + refeeding &; GH treatment (group CRGH). Analysis of GH receptor (GHR), IGF-I, IGF-I receptor (IGF-IR) and IGF binding protein 5 (IGFBP5) expressions by real-time PCR was performed in tibial growth plates extracted at the time of catch-up growth, identified by osseous front advance greater than that of C animals.ResultsIn the absence of GH treatment, catch-up growth was associated with increased IGF-I and IGFBP5 mRNA levels, without changes in GHR or IGF-IR. GH treatment maintained the overexpression of IGF-I mRNA and induced an important increase in IGF-IR expression.ConclusionsCatch-up growth that happens after diet restriction might be related with a dual stimulating local effect of IGF-I in growth plate resulting from overexpression and increased bioavailability of IGF-I. GH treatment further enhanced expression of IGF-IR which likely resulted in a potentiation of local IGF-I actions. These findings point out to an important role of growth cartilage GH/IGF-I axis regulation in a rat model of catch-up growth.     

Predicting growth in response to growth hormone treatment

The use of growth hormone (GH) to treat children who have disturbances of growth is complicated by variability both within and across diagnostic groups, and at the start of and throughout treatment. Growth prediction models are important tools in the effort to account for these sources of variability and tailor GH treatment to each patient’s needs. This review considers the methodological approach taken to the development of models from data in large databases such as the Pfizer International Growth Database (KIGS); it also assesses the limitations of these models and their data sources, and the potential for improvements. While all aspects of model development bear continued scrutiny and improvement, the incorporation of more predictors is key if treatment outcomes are to be optimized in terms of efficacy, safety and cost.