Serum leptin concentration and fuel homeostasis in healthy man

We studied the interrelationship between the obese gene product serum leptin, insulin and counterregulatory hormone concentrations and glycogen synthesis in 26 healthy men. A 4-h euglycaemic insulin clamp with muscle biopsies was performed after a resting control day in 26 subjects, and in 14 of them also after heavy, glycogen-depleting (32%, P < 0.01) exercise. Serum leptin concentrations were at baseline 34% (0.67 ± 0.18 vs. 1.03 ± 0.13 ng L^?1, P ± 0.05) lower after the exercise, and rose during hyperinsulinaemia by 56% (to 1.38 ± 0.19 ng L^?1, P < 0.001) and 34% (to 1.05 ± 0.20 ng L^–1, P < 0.01) after the post-exercise and control studies respectively. Basal serum leptin concentration correlated positively with body mass index (r = 0.42, P < 0.05), serum cortisol concentration (r = 0.70, P < 0.001) and the rise in muscle glycogen content during the clamp (r = 0.43, P < 0.05) and inversely with serum growth hormone concentration (r = ?0.43, P < 0.05). There was a positive correlation between serum leptin after hyperinsulinaemia and serum insulin concentration during the hyperinsulinaemia (r = 0.42, P < 0.05). After exercise, basal serum leptin level correlated with serum triglyceride concentration (r = 0.82, P < 0.001) and after hyperinsulinaemia serum leptin correlated positively with muscle glycogen content (r = 0.56, P < 0.05). It was concluded that serum leptin concentrations correlate directly with serum insulin, cortisol and triglyceride and inversely with growth hormone concentrations. They are decreased by glycogen-depleting exercise and increase during hyperinsulinaemic clamp. These data suggest that leptin is associated with factors regulating fuel homeostasis and its hormonal control in man.     

Angiotensin II induces reduced oxytocin but normal corticotropin release in rats with lesions of the subfornical organ

Summary— The subfornical organ (SFO) was suggested to be the site of the central nervous system which mediates the stimulatory effect of angiotensin II (AII) on corticotropin (ACTH) release. To verify this hypothesis, ACTH response to peripherally administered All was measured in rats with electrolytic lesion of the SFO. Increase in ACTH levels in response to AII (0.5 μg/kg or 2.0 μg/kg iv within 2 min) in conscious cannulated rats was dose-related and it was not affected by SFO lesion. The short infusion of AII (2.0 μg/kg) was enough to induce an elevation in plasma oxytocin. Oxytocin response to AII was reduced while that of aldosterone and blood pressure was not modified by SFO lesion. Our data show that an intact SFO is needed for a full response of oxytocin but not of ACTH release to peripherally injected AII.     

儿童生长激素缺乏症

儿童生长激素缺乏症是导致儿童矮小的原因之一,生长激素激发试验是诊断儿童生长激素缺乏症的重要依据,但也存在假阳性,需要结合生长指标综合评价。生长激素缺乏症分为单纯生长激素缺乏症和多种垂体激素缺乏症,单纯生长激素缺乏症生长激素治疗效果好,需要进行动态的治疗监测,多种垂体激素缺乏症需要激素替代治疗,两者的生长激素缺乏均可能持续至成年期,且单纯生长激素缺乏症可能发展为多种垂体激素缺乏症,需要动态的监测及终身随访。     

生长激素促进大鼠切除左半结肠后剩余结肠的代偿

目的研究左半结肠切除后大鼠剩余结肠的代偿性变化及生长激素对剩余结肠代偿的促进作用。方法首先将健康sD雄性大鼠随机分成三组,切除Ⅰ、Ⅱ组sD大鼠左半结肠10cm,自术后第3天起Ⅱ组sD大鼠每日肌肉注射重组人生长激素,连续10日。21天后活杀取材,通过肉眼、光镜观察剩余结肠的形态改变,并检测结肠粘膜细胞的DNA含量。结果Ⅰ组（术后未用药组）与Ⅲ组（对照组）比较,粘膜增厚,腺上皮分裂细胞增多,肌层增厚。结肠粘膜细胞的DNA含量显著大于对照组（P〈0．05）。Ⅱ组（术后用药组）与I组（术后未用药组）比较,粘膜增厚明显、腺上皮分裂细胞增多,肌层增厚,结构粘膜细胞的DNA含量明显增多（P〈0．01）。结论（1）左半结肠切除后大鼠剩余结肠粘膜处于代偿性增生状态。（2）生长激素对左半结肠切除后大鼠剩余结肠的代偿有极明显促进作用。     

瘦素、瘦素受体和血管内皮生长因子在胃癌中的表达及其在浸润和转移中的作用

目的 探讨瘦素、瘦素受体和血管内皮生长因子（VEGF）在胃癌发展、浸润和转移中的作用及瘦素和VEGF的相互关系。方法 应用免疫组织化学SP法检测20例正常胃黏膜、40例胃癌前病变和60例胃癌组织中瘦素、瘦素受体和VEGF表达情况。结果 瘦素在进展期胃癌组织中的表达明显增强,其阳性率（77．8％）显著高于正常胃黏膜、慢性萎缩性胃炎伴肠化、不典型增生及早期胃癌组织（20．0％、35．0％、45．0％、46．7％,均P〈0．05）;瘦素表达与组织学分级、浆膜浸润和淋巴结转移有关（P〈0．05）。瘦素受体阳性表达率在胃癌发展过程中无统计学意义（P〉0．05）。进展期胃癌组织中VEGF阳性表达率75．6％显著高于正常胃黏膜、慢性萎缩性胃炎伴肠化、不典型增生、早期胃癌组（15．0％、35．0％、45．0％、46．7％,均P〈0．05）IVEGF表达与组织学分级无关（P〉0．05）,与浆膜浸润、淋巴结转移有关（P〈0．05）;瘦素与VEGF在胃癌组织中的表达存在显著正相关关系（r5=0．673,P〈0．01）。结论 瘦素、瘦素受体和VEGF均参与胃癌的发展、浸润和转移。     

Growth hormone replacement therapy induces codeine clearance

BACKGROUND: The increasing clinical use of growth hormone (GH) has raised questions about other than growth-related metabolic effects of this treatment. GH regulates the expression of several hepatic drug metabolising enzymes in the rat, but it is not known whether GH treatment alters the expression of such liver enzymes in man. We have investigated the effects of GH on codeine clearance and two enzymes of the cytochrome P450 (CYP) family, CYP3A and CYP2D6, and UDP-glucuronosyl transferase (UDPGT). These enzymes have a superior importance in hepatic biotransformation of numerous drugs. In addition, CYP3A and UDPGT are catalysts of many reactions with endobiotics such as steroid hormones. METHODS: We used codeine as a probe drug for assessment of the enzyme activities. Codeine was administered as a single-dose prior to, and after 3 months of GH substitution in GH-deficient patients. Total clearance, and clearance along each of the three primary metabolic pathways of codeine, was assessed. RESULTS: Three months of GH substitution increased the total clearance of codeine (21%, P < 0.01) and clearance catalysed by UDPGT significantly (31%, P < 0.05). The treatment tended to increase the clearance via the CYP3A pathway (83%, P = 0.05). CONCLUSIONS: The effects of GH replacement therapy on drug metabolism may have clinical implications when combined with drugs that are substrates of UDPGT and CYP3A. Effects on steroid hormone metabolism with endocrine consequences can not be ruled out.     

A simple, rapid immunometric assay for determination of functional and growth hormone-occupied growth hormone-binding protein in human serum

We present a sensitive time-resolved fluorometric immunofunctional assay (TR-FIA) for direct quantitation of functional growth hormone-binding protein (GHBP), using an immunoassay kit for growth hormone (GH-DELFIA). In addition to the immobilized GH antibody, one monoclonal antibody against GHBP was used. This anti-GHBP was labelled with the chelate of europium. The assay was performed in one step. The detection limit for GHBP was 0.044 nmol L^–1 (NBS + 3 SD). The calibration curve was linear in the interval 0.11–8.03 nmol L^?1. Average intra-assay coefficient of variation (CV) was 3.44%. Average interassay CV at GHBP concentrations 0.563 nmol L^?1 and 1.40 nmol L^?1 were 12% and 6.3% respectively. Analytical recovery in serum ranged from 76% to 127% with a mean of 101 ± 3.6%. Serum GHBP in 102 normal subjects ranged from 0.513 to 3.772 nmol L ¹ and was positively related to body mass index (P < 0.001). In growth hormone-deficient sera GHBP was higher than in control subjects (1.751 ± 0.179 nmol L^?1 and 1.257 ± 0.140 nmol L^?1 respectively, P < 0.001). Acromegalic patients had lower levels of GHBP than controls (0.946 ± 0.251 and 1.234 ± 0.144 nmol L^?1 respectively, P = 0.005). This assay also allowed detection of GH-complexed GHBP in serum. These results were in agreement with theoretical values calculated from the measured GH and the functional GHBP concentrations. Results were compared with data obtained by a recently reported, validated ligand immunofunctional assay (LIFA), which is fundamentally different. There was a significant linear relationship between the results from the two assays (r = 0.89, P = 0.001). The slope of the regression line was 0.65. In conclusion, this new convenient GHBP TR-FIA provides a sensitive and precise method for detecting total GHBP as well as complexed GHBP in human serum, and allows easy processing of large numbers of samples.     

Current therapy and drug pipeline for the treatment of patients with acromegaly

Introduction  Acromegaly is a multisystem disease resulting from chronic exposure to supraphysiological levels of growth hormone (GH), and is associated with significant morbidity and excess mortality. The etiology is almost exclusively an underlying pituitary adenoma. Current therapeutic interventions include surgery, radiotherapy, and medical therapy. Results  Despite surgery, around 50% of patients fail to achieve the biochemical targets shown to correlate with normalization of mortality rates. Radiotherapy is efficacious in controlling tumor growth and GH secretion; still, achievement of biochemical targets may take up to a decade and a number of safety issues have been raised with this treatment modality. Medical therapy, therefore, has an important role as adjuvant therapy in patients who fail to achieve control with surgery, or while awaiting the effects of radiotherapy to be realized. Furthermore, medical therapy is increasingly being used as primary therapy. Current medical therapies include dopaminergic agonists, somatostatin analogs, and GH receptor (GHR) antagonists. Dopaminergic agonists achieve biochemical targets in up to 30% of patients, and somatostatin analogs in around 60%. The currently available GHR antagonist pegvisomant effectively controls insulin-like growth factor-I levels in over 90% of patients; however, it has no effect on the tumor itself and has considerable financial implications. Research into optimizing the somatostatin and dopaminergic systems has led to promising advances in agonist development. Moieties with selectivity for various combinations of somatostatin receptor subtype receptors have been examined, along with molecules that additionally show high affinity for the dopaminergic D2 receptor. Of the molecules studied in vitro, only pasireotide (SOM230) and BIM-23A760 are currently undergoing further development. Other innovations to improve convenience of currently available drugs are also being investigated. Conclusion  Significant advances in under standing of the somatostatin and dopaminergic system have aided drug development. This may lead to new clinically available therapies enabling control of acromegaly in a larger proportion of patients, and at an earlier stage in their disease management.     

生长激素在重度烧伤救治中的作用

目的:观察生长激素在重度烧伤患者救治中对蛋白质代谢,创面愈合及预后中的作用。方法:回顾分析了40例烧伤面积大于50%TBSA的重度烧伤患者,随机分成常规治疗组(对照组),生长激素组(治疗组),了解运用生长激素治疗后对创面愈合和预后的影响。结果:运用治疗组一般情况良好,体重下降减少,植皮区、供皮区愈合时间缩短。结论:生长激素能促进蛋白质合成,缩短创面愈合时间。     

重组人生长激素对中性粒细胞凋亡和存活的影响

目的:研究重组人生长激素(rhG)对有(或)无H LPS刺激的离体培养中性粒细胞(PM N s)凋亡和存活的影响。方法:采健康人外周静脉血,血浆-Percoll不连续密度梯度离心法分离出PM N s,分为4组:对照组,rhG H(100ng/m L)组,LPS100ng/m L组,LPS100ng/m L刺激1h后加rhG H100ng/m L组,离体培养3h和24h上流式细胞仪检测PM N s的凋亡(A nnexin V法)。结果:无LPS刺激状态下,rhG H可引起PM N s早期凋亡率减少、存活率增加,但不影响晚期凋亡/死亡率;有LPS刺激状态下,rhG H不影响PM N s早期凋亡率、晚期凋亡/死亡率和存活率,而且可能对LPS对PM N s刺激有一定阻抑作用。结论:无LPS刺激状态下,rhG H可延迟PM N s凋亡、增强PM N s活力;与LPS共同孵育时,rhG H不影响PM N s凋亡和活力,且对LPS对PM N s的刺激有一定阻抑的作用。     

急性颅脑伤患者血清生长激素、催乳激素、促甲状腺激素放射免疫测定

为了进一步了解急性颅脑伤患者下丘脑-垂体功能的变化,对患者伤后最初3天血清生长激素(GH)、催乳激素(PRL)、促甲状腺激素(TSH)进行了放射免疫测定。结果表明TSH含量均在正常范围,PRL含量伤后最初2天高于正常,而第3天已降至正常,GH含量均高于正常。死亡组伤后第1天PRL含量高于生存组。并对急性颅脑伤患者血清PRL、GH升高的机理进行了探讨,认为可能与下丘脑-垂体的梗塞、坏死及PRL、GH的应激作用有关。     

Erythrocyte fatty acid composition does not influence levels of free,bioavailable, and total 25-hydroxy vitamin D

In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6?±?2.0 years) total 25(OH)D was measured by LC-MS/MS (n?=?78), free 25(OH)D with ELISA (n?=?64 of 78), and bioavailable 25(OH)D was calculated. Analysis of ery-FA composition was by gas chromatography (n?=?56 of 78). A strong correlation between total 25(OH)D and free 25(OH)D was seen (r?=?.66, p?r?=?.68, p?r?=??.33, p?r?=??.47, p?r?=??.44, p?r?=??.35, p?=?.002) and weaker between bioavailable 25(OH)D (r?=??.35, p?=?.040) and free 25(OH)D (r?=??.28, p?=?.079). All fractions of 25(OH)D appear to correlate in a similar way to PTH, BMI and body fat (leptin). No association was found between ery-FA composition and free/bioavailable 25(OH)D. It is unlikely that FAs are a strong uncoupling factor of DBP-bound 25(OH)D.     

Growth hormone and changes in energy balance in growth hormone deficient adults

Background  Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE.
Materials and methods  Nineteen hypopituitary adults (14 males, 5 females, mean age 46·2 years) with severe GHD (peak GH response to glucagon ≤ 9 mU L⁻¹) were studied. All patients self-injected recombinant human GH starting with 0·3 mg s.c. daily. The following were measured before and following 6 months of stable maintenance of GHR: food intake during a test meal, appetite ratings, resting EE (indirect calorimetry) and voluntary physical activity (accelerometry).
Results  GHR nearly doubled voluntary physical activity (mean activity units 3319 vs. 1881, P  = 0·007) and improved quality of life score (mean score 9·1 vs. 16·5, P  < 0·0001). Subjects reported higher fasting hunger ratings (mean 64·8 vs. 49·6, P  = 0·02) but ad libitum energy intake remained unchanged. Eating behavioural traits were favourably altered with lower disinhibition (mean 6·0 vs. 7·2, P  = 0·02) and lower susceptibility to hunger ratings (4·6 vs. 6·8, P  = 0·001) after GHR. Additionally, GHR did not result in significant changes in resting EE, body weight and body mass index.
Conclusions  GHR in AGHD significantly improves voluntary physical activity and quality of life. Following GHR, subjects experience greater 'state' (physiological) hunger, reductions in eating disinhibition and hunger susceptibility, but no effects on calorie intake or macronutrient choice were detected.     

垂体瘤患者术后生长激素激发试验安全性观察与护理

目的 探讨垂体瘤患者术后生长激素激发试验用于诊断成人生长激素缺乏症的安全性与临床护理要点.方法 采用胰岛素耐量试验(insulin telerance test,ITT)作为探测垂体生长激素储备功能的药物激发试验.选择15例垂体瘤术后(无功能性腺瘤和催乳素大腺瘤)患者术后进行ITT试验,行ITT前禁食10 h,静脉注射短效人胰岛素 0.1～0.15 U/kg,于静注短效人胰岛素前30 min、推注前即刻,推注后第30、第45、第60、第90、第120分钟各采血3.5 mL做生长激素及静脉血糖测定,同时监测上述时间点心率及出现低血糖的频率与严重性.结果 血糖低谷主要发生在注射胰岛素后的30～45 min,试验中所有受试者均诱导出生化低血糖,30 min发生低血糖12例,45 min发生低血糖3例,其中需要静脉注射质量浓度50 g/L葡萄糖缓解症状者仅2例.结论 ITT用于诊断生长激素缺乏症过程中低血糖多发生于推注胰岛素后30～45 min,经对症处理后低血糖症状多迅速缓解.试验过程中严密监测血糖可保证试验的安全性.     

婴儿抚触对早产儿血瘦素、IGF-1及骨SOS的影响

目的探讨抚触对早产儿血清瘦素、胰岛素样生长因子（IGF）-1及骨声波速度（SOS）的影响。方法比较分析抚触组、非抚触组（各20例）早产儿组出生3d及纠正胎龄40周时体重、身长、血瘦素、IGF-1及超声测定左胫骨SOS的结果。结果出生3d时早产儿抚触组与非抚触组的体重、身长、骨SOS、血清瘦素及IGF—1比较,差异均无统计学意义（t分别=0．38、0．37、0．42、1．28、0．76,P均〉0．05）。纠正胎龄满40周时,抚触组的体重、骨SOS及血清瘦素明显高于非抚触组,差异均有统计学意义（t分别=2．06、7．69、3．37,P均〈0．05）;而抚触组的身长和IGF—1与非抚触组比较,差异均无统计学意义（t分别=1．82、2．27,P均〉0．05）。结论抚触能够减缓早产儿出生以后骨SOS的下降、促进体重增加和血清瘦素水平提高。     

烧伤儿童短期生长激素治疗的效果

目的探讨烧伤儿童短期给予生长激素阻止生长延迟的效果。方法住院期接受生长激素治疗的烧伤儿童为生长组,未接受生长激素治疗的为对照组,对比两组儿童的身高情况。所得数据经统计学分析。结果治疗开始初,烧伤后6个月时,生长组和对照组的身高平均值没有区别。然而,烧伤后2年时,生长组和对照组的身高值有明显的差异(P<0.05)。结论住院期间给予生长激素的严重烧伤儿童没有出现明显的生长延迟,保持了身高的增长。     

严重烧伤病人应用重组人生长激素的护理

笔报道对88例严重烧伤患应用重组人生长激素的观察及护理,提出护理重点在于掌握药物的配制、储存要求,认真做好注射部位的选择,密切观察用药反应,加强对症处理,注意用药量及禁忌证,是确保其治疗效果和减少副作用的关键。